Biomedical subjects
Publications and source records attributed to J M O'Brien.
Common dermatological problems as a frequent presenting complaint are stratified by infancy, childhood, and adolescence. The common manifestations and questions asked by parents are discussed. Both infectious and noninfectious rashes are included. Convenient treatment modalities are listed.
Epidural analgesia offers a highly effective route of providing acute pain relief. As this mode of medication delivery is used more frequently in the acute care setting, nurses must acquire theoretical knowledge, apply monitoring parameters, and demonstrate technical competency. Implementing a self-learning packet to educate nursing staff caring for patients receiving epidural analgesia is an effective teaching medium and can help improve clinical performance.
Uveal melanoma cell cycling, quantified by bromodeoxyuridine (BrdUrd)-labeling index and mitotic index, is predictive of tumor-related mortality. Serial sections from 36 formalin-fixed melanoma specimens were labeled with BrdUrd and stained with hematoxylin and eosin. All tumors were assessed for the area of highest cell cycling activity and counts for mitotic figures and BrdUrd labeling were performed in these areas in a masked manner. The BrdUrd labeling index and mitotic index were calculated and analyzed in relation to tumor-related mortality and histopathological criteria (largest tumor diameter, cell type, extra-scleral extension, ocular location). Cox multivariate analysis estimated an increased relative risk of tumor-related mortality of 2. 32 (95% confidence interval, 1.22-4.41) per doubling of BrdUrd labeling index and 2.41 (95% confidence interval, 1.29-4.49) per doubling mitotic index. Larger tumors, nonspindle cell tumors, and anterior-located tumors tended to have higher cycling rates.
Genomic instability appears to play an important role in the development, growth, invasiveness, and eventual metastasis of the neoplastic cell. We have used a powerful new technique, comparative genomic hybridization, to evaluate genetic alterations in 10 fresh frozen uveal melanomas. Comparative genomic hybridization utilizes dual fluorescence in situ hybridization to characterize chromosome deletions and duplications, allowing for simultaneous evaluation of the entire human genome. Several consistent chromosomal abnormalities were detected. This study confirmed previous findings obtained using standard cytogenetic techniques but demonstrated an increased incidence in abnormalities of chromosomes 3 and 8; there was loss of chromosome 3 and duplication of 8q. In addition, we identified, although less frequently, other recurrent abnormal regions including alterations on chromosomes 6p, 7q, 9p, and 13q.
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OBJECTIVE: Our purpose was to determine whether the presence of prolactin in cervicovaginal washings is associated with preterm birth. STUDY DESIGN: A cohort of 80 patients underwent a washing of the ectocervix and vaginal fornices with a normal saline solution. The cohort consisted of two groups: 40 inpatients requiring tocolysis and 40 asymptomatic outpatients. The saline solution aspirates were centrifuged, the supernatant was stored at -70 degrees C, and a radioimmunoassay for prolactin was run in batch fashion. A prolactin concentration greater than the detection limit of the assay was considered a positive test result. RESULTS: Prolactin was identified in significantly more symptomatic patients than asymptomatic controls (50% vs 5%, p < 0.0001). In symptomatic patients cervicovaginal prolactin had an 80% positive predictive value and a 65% negative predictive value for delivery at < or = 34 weeks' gestation. Patients testing positive for prolactin had significantly shorter latency from testing to delivery (16 +/- 17 vs 34 +/- 24 days, p = 0.02) and had significantly lower birth weights (1985 +/- 729 vs 2583 +/- 696 gm, p = 0.01) compared with patients testing negative. Prolactin was also identified in two asymptomatic patients, both of whom were delivered before term. CONCLUSIONS: Cervicovaginal prolactin is a biochemical marker for preterm delivery, a shorter latency period to delivery, and lower birth weight in symptomatic patients. This test may also prove to be a valuable marker for preterm birth in asymptomatic women.
Thyroid ophthalmopathy, idiopathic orbital inflammation, and orbital infection can occasionally demonstrate overlapping clinical features. It is essential to distinguish between these processes because appropriate treatments are distinct in each case. In the past year, the pathophysiology of thyroid ophthalmopathy has been the topic of many reports. Orbital inflammation, particularly the fibrotic form, has been recognized to represent a distinct disease entity that may require more specifically directed treatment. In some cases cytotoxic therapies may be indicated. Orbital infection, particularly in the setting of orbital abscess, may be treated conservatively with antibiotic therapy and observation or more aggressively with surgical drainage procedures. In several recent studies, appropriate management of such infectious processes appears to be related to patient age, as well as to the specific clinical pattern of presentation.
Recent changes in the NHS have left many defects in the systems for the control of communicable diseases and infection and their surveillance and the management of outbreaks. Clear, explicit legislation is needed, placing the responsibilities on health authorities. New teams led by consultants need to be set up to investigate and manage outbreaks of communicable diseases of all types.
The Saccharomyces cerevisiae Cdc42 protein, a member of the Ras superfamily of low-molecular-weight GTP-binding proteins, is involved in the control of cell polarity during the yeast cell cycle. This protein has a consensus sequence (CAAX) for geranylgeranyl modification and is likely to be associated, at least in part, with cell membranes. Using cell fractionation and immunolocalization techniques, we have investigated the subcellular localization of Cdc42p. Cdc42p was found in both soluble and particulate pools, and neither its abundance nor its distribution varied through the cell cycle. The particulate form of Cdc42p could be solubilized with detergents but not with NaCl or urea, suggesting that it is tightly associated with membranes. An increase in soluble Cdc42p was observed in a geranylgeranyltransferase mutant strain (cdc43-2ts) grown at the restrictive temperature. In addition, Cdc42p from a cdc42C188S mutant strain (that has an alteration at the prenylation consensus site) was almost exclusively in the soluble fraction, suggesting that membrane localization is dependent on geranylgeranyl modification at Cys-188. Immunofluorescence and immunoelectron microscopy experiments demonstrated that Cdc42p localizes to the plasma membrane in the vicinity of secretory vesicles that were found at the site of bud emergence, at the tips and sides of enlarging buds, and within mating projections (shmoo tips) in alpha-factor-arrested cells. These results indicate that Cdc42p is localized to the bud site early in the cell cycle and suggest that this localization is critical for the selection of the proper site for bud emergence and for polarized cell growth.
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OBJECTIVE: To determine the relationship between low amniotic fluid (AF) index and fetal growth retardation (FGR), fetal distress, and cesarean delivery in patients hospitalized for hypertensive disease, and to describe changes in AF status in relation to the severity of maternal disease. METHODS: The AF index in 142 hospitalized hypertensive patients was followed per an inpatient protocol with semi-weekly testing; medical records were reviewed to obtain delivery data. RESULTS: Fetal growth retardation was significantly associated with an AF index of 5.0 cm or less or 7.0 cm or less (P < .001) at initial assessment, with positive predictive values of 86 and 52%, respectively. However, the sensitivity of an AF index of 5.0 cm or less or 7.0 cm or less to detect FGR was limited (21 and 46%, respectively). Fetal distress and cesarean delivery were not associated with an AF index of 5.0 cm or less or 7.0 cm or less throughout observation in this cohort. Based upon a definition of oligohydramnios as an AF index of 7.0 cm or less, the AF status worsened from an initial normal value in 39% of patients whose final diagnosis was severe preeclampsia, versus only 14% of patients who were diagnosed as having mild disease. The AF index also normalized in ten patients who were originally diagnosed with oligohydramnios and admitted for expectant management. Only one of these women was diagnosed with severe preeclampsia. CONCLUSIONS: 1) Depending on the definition, the incidence of oligohydramnios ranges from 10-30% in hypertensive patients requiring hospitalization; 2) an AF index of 5.0 cm or less at initial evaluation predicts FGR but lacks sensitivity; 3) the AF status frequently changes with serial assessment, and these changes appear to be related to the severity of hypertensive disease; and 4) the frequency of the obstetric complications studied depends more upon the severity of hypertensive disease than on its potential effect of inducing oligohydramnios.
PURPOSE: Genetic alterations have been observed in a wide variety of neoplastic processes, including Burkitt's lymphoma, chronic myelogenous leukemia, promyelocytic leukemia, and solid tumors of the colon, skin, and breast. The polymerase chain reaction (PCR), dot blotting, and direct double-stranded DNA sequencing were used to assess ras gene activation in human uveal melanomas for three candidate genes: c-Ha-ras1, c-Ki-ras2, and N-ras at codons 12, 13, and 61. METHODS: Samples of 49 human uveal melanomas were obtained. Amplifiable high molecular weight DNA was obtained from 39 of these. PCR amplification of regions centering on three candidate ras genes was performed. PCR-amplified DNA was evaluated by dot blot and double-stranded DNA sequencing utilizing standard methods. RESULTS: No point mutations were identified in screening the c-Ha-ras gene nor were any genetic alterations found in the c-Ki-ras2 gene at codons 12 and 13. Only wild-type sequences were found at codon 61. No ras mutations were detected in any uveal melanomas studied. CONCLUSIONS: This study provides no evidence to support an association between ras protooncogene mutations and human uveal melanomas at codons 12, 13, or 61.
The amphipathic dye, merocyanine 540 (MC540), which preferentially photosensitizes enveloped viruses and virus-infected cells, is currently being evaluated in preclinical models as a blood sterilizing agent. In this communication, we report on an initial analysis of the site and nature of MC540-mediated photodynamic damages to human herpes simplex virus type 1 and human cytomegalovirus. The comigration of dye molecules and virions on a gel filtration column, the red-shift of the fluorescence emission spectrum of virus-containing fractions, and the distribution of MC540-treated virions in an aqueous two-phase partition system were indicative of MC540 binding to the enveloped viruses and localizing in a lipophilic environment (most likely the viral envelope). Fluorescence quenching and fluorescence resonance energy transfer experiments suggested that both dye monomers and dimers were capable of partitioning into the lipid bilayer of the viral envelope. Adsorption and penetration assays and immunohistochemical analyses of viral antigen expression showed that MC540-sensitized irradiation interfered with early phases of the infectious process, the adhesion to the host cell, the penetration of the host cell, and the translocation of the virus into the nucleus of the host cell. The inactivation of viruses was inhibited if oxygen in the medium was displaced by argon, enhanced if air was displaced by pure oxygen or if water was replaced by deuterium oxide. This suggested that the MC540-sensitized photoinactivation of enveloped viruses is an oxygen-dependent process and that singlet oxygen is one but not necessarily the only mediator of the antiviral effects of MC540.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
A wide range of enveloped viruses, including human herpes simplex virus type 1, human cytomegalovirus, human T cell leukemia/lymphoma virus type I, human immunodeficiency virus type 1, Sindbis virus, and Friend erythroleukemia virus, are highly susceptible to merocyanine 540 (MC 540)-sensitized photoinactivation. By contrast, human pluripotent hematopoietic stem cells, red cells, factor VIII, and von Willebrand factor are much less sensitive. This suggests that MC 540 may be useful for the inactivation of enveloped viruses in blood and blood products. The dye has a low acute systemic toxicity, is rapidly eliminated from the blood stream, and has little or no mutagenic potential. The currently available data support the view that MC 540-sensitized photo-inactivation interferes with early events in the infectious process, notably the ability of the virus to adhere to and penetrate its host cell. The viral envelope is a major target of photodynamic damages which appear to be mediated at least in part by singlet molecular oxygen.