Search PubMed⌕ Search

Biomedical subjects

D Miller

Publications and source records attributed to D Miller.

At least 109 records · Page 6Linked to original sources
PubMed2000

The p53 codon 72 polymorphism and lung cancer risk.

The p53 tumor suppressor gene frequently is mutated in many forms of human carcinomas. A common polymorphism occurs at codon 72 of exon 4, with two alleles encoding either arginine (CGC) or proline (CCC). This p53 polymorphism reportedly is associated with lung cancer susceptibility. However, not all investigations have been consistent, and this hypothesized association remains controversial. We tested the hypothesis that the Pro/Pro genotype is associated with increased lung cancer risk in a large case-control study of lung cancer that included 482 cases and 510 controls from the Massachusetts General Hospital in Boston, Massachusetts. DNA from peripheral blood samples was examined by PCR-RFLP. Pro/Pro homozygotes were found more frequently in adenocarcinomas (cases, 16.4%; controls, 12.0%; P = 0.03). The prevalence of the Pro/Pro homozygous genotype increased in frequency with increasing pack-years of smoking. The combined susceptible genotype homozygous Pro/Pro and heterozygous Arg/Pro was associated with a 1.45-fold higher risk of adenocarcinoma compared with Arg/Arg genotype (95% confidence interval = 1.01-2.06; P = 0.04) after adjustment for relevant variables. Lung adenocarcinoma risk increased with the presence of one or both variant alleles across smoking strata. In addition, at each level of smoking (except nonsmoker and light smoker), the risk associated with smoking was higher for the population with the combined variant (Arg/Pro + Pro/Pro) genotype. The risk for the combined genotype was associated with tobacco exposure status. In conclusion, the codon 72 germ-line polymorphism (Arg/Pro) of the common tumor suppressor gene p53 contributes to heritable susceptibility for smoke-induced lung adenocarcinoma. The modifications by p53 polymorphism and pack-years resulted in an increased risk of the susceptible genotype to lung adenocarcinoma. The p53 gene may modulate the response to environment carcinogens and thereby affect the risk of developing lung adenocarcinoma.

Adenocarcinoma↗
PubMed1999

Relation between lesion characteristics and risk with percutaneous intervention in the stent and glycoprotein IIb/IIIa era: An analysis of results from 10,907 lesions and proposal for new classification scheme.

BACKGROUND: The currently used American College of Cardiology/American Heart Association lesion classification scheme dates from an era when balloon angioplasty was the only percutaneous treatment available and major complications occurred in approximately 7% of patients. Major advances in treatment options would suggest that this scheme may be outmoded, but the schemes that have been suggested to update lesion classification have not been widely accepted. METHODS AND RESULTS: Four thousand one hundred eighty-one consecutive patients (6,676 lesions) formed a training set and 2,146 patients (4,231 lesions) formed a validation set treated from 1995 to 1997 at a single center used by 3 hospital groups. Twenty-seven pretreatment candidate variables were analyzed with the use of stepwise proportional logistic regression, and 9 (nonchronic total occlusion with TIMI flow 0, degenerated vein graft, vein graft age >10 years, lesion length >/= 10 mm, severe calcium, lesion irregularity, large filling defect, angulated >/= 45 degrees plus calcium, and eccentricity) were independently correlated (P<0.05) with ranked adverse outcome (death, Q-wave or creatine kinase >/= 3x normal myocardial infarction, or emergency coronary artery bypass grafting>>creatine kinase 2 to 3x myocardial infarction>>possibly related to non-Q-wave myocardial infarction>>no complication). A scheme based on these findings and the old American College of Cardiology/American Heart Association scheme were found to have c-statistics in the validation set of 0.672 and 0.620 (P = 0.010 vs old scheme), respectively. CONCLUSIONS: Appreciation of these contemporary risk factors for complications of coronary intervention may assist in patient selection and in risk adjustment for comparison of outcomes between providers.

Adult↗
PubMed1999

A complex population of RNAs exists in human ejaculate spermatozoa: implications for understanding molecular aspects of spermiogenesis.

The presence of mRNAs in human ejaculate spermatozoa is well established, yet little is known of the representation or function of these transcripts. To address these issues, the complexity of spermatozoal RNA was examined. As expected, testis-expressed mRNAs were detected by RT-PCR in mature human spermatozoa. Interestingly, when a testis cDNA library was probed with total spermatozoal RNA, less than 2% of plaques gave a strong hybridization signal, suggesting a rather unique sperm-derived population. To further define the sequence distribution, 18 strongly hybridizing clones were selected at random for end-sequence analysis. Twelve matched unique sequences in the EST, STS and NR databases, whereas five showed no similarity to any of the sequences in the databases. In addition, one clone belonged to the SINE repetitive element family. As demonstrated by sequencing randomly primed cloned inserts, short (SINE/MER) or long (LINE/ORF2) interspersed repeat-like sequences are also contained as part of the spermatozoal RNA fraction. It is now evident that human spermatozoa contain a rich repertoire of both known and unknown protein-encoding and non-coding RNAs. This provides a unique opportunity to identify and investigate the many genes responsible for the structure and function/dysfunction of the male gamete using spermatozoal RNA as the template.

Amino Acid Sequence↗
PubMed1999

Environmental engineering: energy value of replacing waste disposal with resource recovery

Although in the past, environmental engineering has been primarily concerned with waste disposal, the focus of the field is now shifting toward viewing wastes as potential resources. Because reclamation usually consumes less energy than producing new materials, increasing reclamation not only reduces pollution but saves energy. Technological innovations contributing to this shift are summarized here, and are variously classified as emerging technologies or research topics, as either new departures or incremental improvements, and as opportunistic innovations, or examples of a unifying strategy. Both liquid and solid waste examples are given, such as a recent discovery of effects in disinfecting microfiltered reclaimed wastewater with ultraviolet light. In addition to its value in reducing pollution and conserving energy, this reorientation of environmental engineering could contribute to a more general shift toward greater cooperation among organizations dealing with the environment.

Journal Article↗
PubMed1999

General practice and the care of children with HIV infection: 6 month prospective interview study.

OBJECTIVES: To describe the use of primary care services by children infected with HIV and to explore the attitudes of their parents to the role of general practitioners in their children's care. DESIGN: A 6 month prospective study. Quantitative analysis of "contact diaries" kept by parents; qualitative analysis of face to face interviews with parents. PARTICIPANTS: Parents of children receiving care at a regional referral centre in London. RESULTS: Twenty four families (80% response rate) were recruited to the study. In 19 families the mother was black African. Half the children had been diagnosed with symptomatic HIV infection, half with AIDS. All the children were registered with a general practitioner who knew of the child's HIV infection. In five families there had initially been tensions in their relationship with their general practitioner but by the time of the study all but one family had established at least an "acceptable" relationship. Children with symptomatic HIV infection saw their general practitioner a mean of 7.5 times per patient year; for children with AIDS the figure was 5.8. Parents regarded the paediatric HIV team at the hospital as their primary source of medical care. Three factors constrained their use of general practice: their own anxieties about distinguishing "normal" symptoms from those related to HIV infection; their view that their general practitioner did not feel competent to treat HIV infected children; and their concerns about maintaining confidentiality in the surgery. CONCLUSIONS: Parents remain oriented towards the paediatric HIV team as their primary source of medical care and use general practice largely for routine prescriptions for their children. Any further development of the general practitioner's role will need to build on existing relationships with specialist providers and take account of parents' concerns.

Child↗
PubMed1999

Predictive value of gadolinium-enhanced magnetic resonance imaging for relapse rate and changes in disability or impairment in multiple sclerosis: a meta-analysis. Gadolinium MRI Meta-analysis Group.

BACKGROUND: Reliable prognostic factors are lacking for multiple sclerosis (MS). Gadolinium enhancement in magnetic resonance imaging (MRI) of the brain detects with high sensitivity disturbance of the blood-brain barrier, an early event in the development of inflammatory lesions in MS. To investigate the prognostic value of gadolinium-enhanced MRI, we did a meta-analysis of longitudinal MRI studies. METHODS: From the members of MAGNIMS (European Magnetic Resonance Network in Multiple Sclerosis) and additional centres in the USA, we collected data from five natural-course studies and four placebo groups of clinical trials completed between 1992 and 1995. We included a total of 307 patients, 237 with relapsing disease course and 70 with secondary progressive disease course. We investigated by regression analysis the relation between initial count of gadolinium-enhancing lesions and subsequent worsening of disability or impairment as measured by the expanded disability status scale (EDSS) and relapse rate. FINDINGS: The relapse rate in the first year was predicted with moderate ability by the mean number of gadolinium-enhancing lesions in monthly scans during the first 6 months (relative risk per five lesions 1.13, p=0.023). The predictive value of the number of gadolinium-enhancing lesions in one baseline scan was less strong. The best predictor for relapse rate was the variation (SD) of lesion counts in the first six monthly scans which allowed an estimate of relapse in the first year (relative risk 1.2, p=0.020) and in the second year (risk ratio=1.59, p=0.010). Neither the initial scan nor monthly scans over six months were predictive of change in the EDSS in the subsequent 12 months or 24 months. The mean of gadolinium-enhancing-lesion counts in the first six monthly scans was weakly predictive of EDSS change after 1 year (odds ratio=1.34, p=0.082) and 2 years (odds ratio=1.65, p=0.049). INTERPRETATION: Although disturbance of the blood-brain barrier as shown by gadolinium enhancement in MRI is a predictor of the occurrence of relapses, it is not a strong predictor of the development of cumulative impairment or disability. This discrepancy supports the idea that variant pathogenetic mechanisms are operative in the occurrence of relapses and in the development of long-term disability in MS.

Adolescent↗
PubMed1999

Distance and near visual acuity, contrast sensitivity, and visual fields of 10-year-old children.

OBJECTIVE: To measure monocular distance visual acuity, near visual acuity, contrast sensitivity, and visual field extent in full-term, 10-year-old children tested according to the protocol used to test 10-year-old preterm children in the Cryotherapy for Retinopathy of Prematurity study. SUBJECTS AND METHODS: Subjects were 106 healthy, full-term children, 9.8 to 10.9 years of age, who had no ocular abnormalities other than ametropia. All were tested monocularly using Early Treatment and Diabetic Retinopathy Study distance and near visual acuity charts and Pelli-Robson contrast sensitivity charts, with refractive error corrected according to Cryotherapy for Retinopathy of Prematurity study criteria. Goldmann perimetry was tested without correction using the V-4-e and III-4-e stimuli along 8 meridia. A standard pediatric eye examination was performed on each subject. RESULTS: Mean (SD) distance visual acuity was 20/19.6 OD (0.082 log unit [lu]) and mean near visual acuity was 20/19.5 OD (0.100 lu). Mean (SD) contrast sensitivity was 1.69 OD (0.12 lu), with a mean (SD) of 36.4 (2.2) letters read. Visual field extent was larger for the V-4-e stimulus than for the III-4-e stimulus. CONCLUSIONS: The results provide the first monocular normative data from a large sample of 10-year-old children tested with Early Treatment and Diabetic Retinopathy Study distance and near visual acuity charts and the Pelli-Robson contrast sensitivity charts, and add to the literature on Goldmann perimetry in children.

Child↗
PubMed1999

Monoclonal antibody treatment exposes three mechanisms underlying the clinical course of multiple sclerosis.

The elective treatment of patients with multiple sclerosis, using a humanized anti-leukocyte (CD52) monoclonal antibody (Campath-1H), has illuminated mechanisms that underlie the clinical course of the disease. Twenty-seven patients were studied clinically and by magnetic resonance imaging (MRI) before and for 18 months after a single pulse of Campath-1H. The first dose of monoclonal antibody was associated with a transient rehearsal of previous symptoms caused by the release of mediators that impede conduction at previously demyelinated sites; this effect remained despite selective blockade of tumor necrosis factor-alpha. Disease activity persisted for several weeks after treatment but thereafter radiological markers of cerebral inflammation were suppressed for at least 18 months during which there were no new symptoms or signs. However, about half the patients experienced progressive disability and increasing brain atrophy, attributable on the basis of MRI spectroscopy to axonal degeneration, which correlated with the extent of cerebral inflammation in the pretreatment phase. These data support the formulation that inflammation and demyelination are responsible for relapses of multiple sclerosis; that inflammatory mediators, but not tumor necrosis factor-alpha, cause symptomatic reactivation of previously demyelinated lesions; and that axonal degeneration, conditioned by prior inflammation but proceeding despite its suppression, contributes to the progressive phase of disability. These results provide evidence supporting the emerging view that treatment in multiple sclerosis must be given early in the course, before the consequences of inflammation are irretrievably established.

Adult↗
PubMed1999

Oligodendroglial gliomatosis cerebri: (1)H-MRS suggests elevated glycine/inositol levels.

Oligodendroglial gliomatosis cerebri is very rare. We describe 42-year-old woman who had low-grade oligodendroglial gliomatosis cerebri confirmed on stereotactic biopsy. The diffuse nature of the tumour was apparent clinically, neurophysiologically, on MRI and on proton magnetic resonance spectroscopy (MRS). She also had an isolated, false-localising partial seventh nerve palsy. MRS, of which there are no previous reports, suggested elevated glycine/inositol levels. This might be explained by the cell lineage from which the tumour arose.

Adult↗
PubMed1999

Hypomagnesemia in trauma patients.

The objective of this study was to determine the incidence of hypomagnesemia in injured patients (versus a general hospital cohort) and to compare total and ionized values with each other and with the incidence of injury severity and ethanol level. It was a descriptive study of consecutive injured patients at a level II trauma center. For 3 months subjects underwent admission paired analysis of blood total magnesium (TMg) and ionized magnesium (IMg). IMg was determined by microanalysis of whole blood (Nova Biomedical, NovaSP9). During the same time period, all hospital samples for TMg (m = 1308) underwent simultaneous IMg testing. Pearson correlation coefficients were determined for IMg versus TMg, Injury Severity Score (ISS), Trauma Score (TS), Glasgow Coma Scale (GCS), and blood units transfused. By convention, hypomagnesemia was defined as TMg < or =1.6 mg/dl and IMg < or = 0.5 mg/dl. Altogether 43% of 113 trauma patients had low magnesium levels compared to 30% of noninjured cohorts (p<0.05). The correlation coefficient (r(2)) for TMg and IMg was 0.74 for TMg values >1.6, but for TMg < or =1.6 the r(2) was 0.35. Coefficients for IMg and ISS, TS, GCS, units transfused, and ethanol level were 0.06, 0.08, 0.10, 0.04, and 0.01, respectively. Mean IMg was 0.57+/-0.09 mg/dl with ethanol ingestion and 0.56+/-0.06 mg/dl without ethanol ingestion (mean +/- SD, p>0.05). It was concluded that hypomagnesia is common in injured patients but does not correlate with indices of injury severity or ethanol level. TMg is not a good predictor of IMg at low levels. Trauma patients may benefit from determination of IMg for accurate diagnosis of a low Mg level to facilitate repletion.

Adult↗
PubMed1999

Evolution of homeobox genes: Q50 Paired-like genes founded the Paired class.

The genes belonging to the Paired class exert primary developmental functions. They are characterized by six invariant amino acid residues in the homeodomain, while the residue at position 50 can be a serine, glutamine or lysine as in the Pax-type, Q50 Paired-like or the K50 Paired-like homeodomains respectively. Genes in this class emerged early in animal evolution: three distinct Pax genes and two Q50 Paired-like genes have recently been characterised from cnidarians. Phylogenetic molecular reconstructions taking into account homeodomain and paired-domain sequences provide some new perspectives on the evolution of the Paired-class genes. Analysis of 146 Paired-class homeodomains from a wide range of metazoan taxa allowed us to identify 18 families among the three sub-classes from which the aristaless family displays the least diverged position. Both Pax-type and K50 families branch within the Q50 Paired-like sequences implying that these are the most ancestral. Consequently, most Pax genes arose from a Paired-like ancestor, via fusion of a Paired-like homebox gene with a gene encoding only a paired domain; the Cnidaria appear to contain genes representing the 'before' and 'after' fusion events.

Animals↗
PubMed1999

Emerging ciprofloxacin-resistant Pseudomonas aeruginosa.

PURPOSE: To report a clinical series of ciprofloxacin-resistant ocular isolates of Pseudomonas aeruginosa from a tertiary care ophthalmic center. METHODS: Review of in vitro sensitivities of all ocular isolates of P. aeruginosa be tween July 1991 and September 1998. In vitro resistance was defined as a minimum inhibitory concentration of 4 or more microg per ml. RESULTS: Nine of 423 ocular isolates of P. aeruginosa showed in vitro resistance to ciprofloxacin. From 1991 to 1994, 0.44% (1/227) of ocular isolates were resistant to ciprofloxacin, whereas from 1995 to 1998, 4.1% (8/ 196) of ocular isolates showed in vitro resistance (P = .014). CONCLUSIONS: Ciprofloxacin-resistant P. aeruginosa has been identified in recent clinical ocular specimens. Ciprofloxacin resistance among ocular isolates of P. aeruginosa is a local and worldwide concern.

Anti-Infective Agents↗
PubMed1999

Juvenile hormone titers in virgin and mated Choristoneura fumiferana and C. rosaceana females: assessment of the capacity of males to produce and transfer JH to the female during copulation.

We used a radioimmunoassay (RIA) to assess the effect of mating on juvenile hormone (JH) titer in females of the tortricid moths Choristoneura fumiferana and C. rosaceana. Virgins had undetectable levels of JH in their hemolymph on the 5th day of the pupal stage but titers rose to 1-4 and 0.2-0.5 ng JH II eq./ml, respectively, after emergence. On days 1, 3 and 5 following copulation, females of both species had higher JH titers than virgins of the same ages, with the greatest difference between virgin and mated females observed on day 3 for C. fumiferana and on day 5 for C. rosaceana. This increase was apparently not the result of a male-to-female transfer of JH during copulation since: (i) the accessory sex glands (ASGs) of males of both species displayed a very limited ability to convert JH acid into JH, (ii) ASGs produced no JH when incubated in vitro in the presence of L-[methyl-(3)H]-methionine, (iii) ASGs of males injected with L-[methyl-(3)H]-methionine 24 h prior to dissection contained no JH-associated radioactivity, and (iv) freshly formed spermatophores dissected out of females mated to similarly injected males contained no trace of radioactive JH. In addition, the JH content of ASGs and spermatophores, as measured by RIA, was not higher than that of virgin-female hemolymph, on a per-mg basis. However, in contrast with earlier findings in other species of moths, the CA of male C. fumiferana and C. rosaceana maintained in vitro in the presence of tritiated methionine produced and released JH I, JH II and JH III in quantities and proportions similar to those reported for female glands.

Journal Article↗