Biomedical subjects
D Miller
Publications and source records attributed to D Miller.
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.
Sphingosylphosphorylcholine is a bona fide mediator regulating heart rate.
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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.
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.
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.
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.
Chemoreduction and local ophthalmic therapy for intraocular retinoblastoma.
PURPOSE: To study the effectiveness of combined systemic chemotherapy and local ophthalmic therapy for retinoblastoma with the goal of avoiding enucleation and external-beam radiation therapy (EBRT). PATIENTS AND METHODS: This was a prospective, nonrandomized, single-arm clinical trial. Seventy-five eyes were followed in 47 children. Patients were treated with a six-cycle protocol of vincristine, etoposide, and carboplatin. Most (83%) also received ophthalmic treatment (cryotherapy, laser photocoagulation, thermotherapy, or plaque radiation therapy) during and/or after the chemotherapy. RESULTS: With a median follow-up of 13 months, event-free survival was 74%, with an event defined as enucleation and/or EBRT. Six children required EBRT in seven eyes (9%); five required enucleation of one eye (7%); five required a combination of EBRT and enucleation in six eyes (8%). Reese-Ellsworth groups 1, 2, and 3 eyes had excellent results, with avoidance of EBRT or enucleation in all 39. Treatment of groups 4 and 5 was less successful, with 33% of six eyes and 53% of 30 eyes, respectively, requiring EBRT and/or enucleation. Toxicities from chemotherapy were mild and included cytopenias (89%), fever and neutropenia (28%), infection (9%), and gastrointestinal symptoms, dehydration, and vincristine neurotoxicity (40%). No patients developed a second malignancy, metastatic disease, renal disease, or ototoxicity. CONCLUSION: In retinoblastoma patients with Reese-Ellsworth eye groups 1, 2, or 3, systemic chemotherapy used with local ophthalmic therapies can eliminate the need for enucleation or EBRT without significant systemic toxicity. More effective therapy is required for Reese-Ellsworth eye groups 4 and 5.
Dissecting thoracoabdominal aortic aneurysm in a free-ranging Florida panther (felis concolor coryi).
A 12-yr-old female free-ranging Florida panther (Felis concolor coryi) was found dead in good flesh. The panther had a ruptured thoracoabdominal aneurysm and 0.5 L of unclotted blood in its thorax. Intimal plaques 6.0 x 3.0 x 3.0 cm and 4.0 x 3.0 x 1.0 cm were present in the thoracic and abdominal aorta extending below the bifurcation of the renal arteries. Histologic examination revealed necrohemorrhagic aortitis with a mixed inflammatory infiltrate of lymphocytes, macrophages, and neutrophils. Death was almost certainly due to exsanguination and hypovolemic shock secondary to the ruptured aneurysm, and the aortitis with the resultant aneurysm may have been secondary to an infectious or a toxic process. This is the first reported death of a free-ranging mammal from a ruptured aortic aneurysm.
Student and staff relationships in a clinical practice model: impact on learning.
This qualitative study describes the perspectives of diploma nursing students and staff nurses on the student-staff relationship and the impact this relationship has on student learning. Staff and students, working in a clinical practice model setting in a large urban hospital, participated in focused interviews following a 15-week clinical practice assignment. Findings revealed there were several commonalities in staff and student perceptions of the relationship. Both staff and students described role perception, staff characteristics, and the workplace environment as important factors influencing the relationship and student learning. Students also identified working in a collegial relationship as being important to learning and their socialization into the nursing profession.
Patterns of treatment of patients with prostate cancer initially managed with surveillance: results from The CaPSURE database. Cancer of the Prostate Strategic Urological Research Endeavor.
PURPOSE: We determined the demographic and clinical profile of men who elect surveillance as the initial management of prostate cancer as well as the incidence and predictors of secondary treatment of these patients. MATERIALS AND METHODS: The Cancer of the Prostate Strategic Urological Research Endeavor (CaPSURE) is a national disease registry of patients with various stages and treatments of prostate cancer. Using this database of 4,458 men we identified 329 (8.2%) who elected surveillance as the initial management of prostate cancer. Patients choosing watchful waiting were compared to other CaPSURE participants using the chi-square test. The likelihood of treatment initiation in the watchful waiting group was calculated using the Kaplan-Meier method. After adjusting for patient age, race, prostate specific antigen (PSA) at diagnosis, clinical T stage and total Gleason score the Cox proportional hazards regression model was used to determine significant predictors of treatment initiation. RESULTS: Compared with others in the database, patients on watchful waiting were more likely to be 75 years old or older (51% versus 16%, p <0.001), white (93% versus 85%, p <0.001), and have lower serum PSA (p <0.001), organ confined disease (97% versus 88%, p <0.001) and a total Gleason score of 7 or less (97% versus 88%, p <0.001). In the watchful waiting group there was a 52% likelihood of treatment initiation within 5 years of the diagnosis. Significant predictors of secondary treatment were age younger than 65 years and elevated serum PSA at diagnosis. Neither race, extraprostatic stage cT3 disease nor higher total Gleason score was a significant predictor of treatment. CONCLUSIONS: Men who elect initial watchful waiting for prostate cancer tend to be older, have lower serum PSA and more favorable disease characteristics than those who seek treatment. PSA at diagnosis is the dominant factor for predicting secondary treatment.
Comprehensive gynecologic endoscopic hospital privileging program. Implementation and assessment.
OBJECTIVE: To describe a comprehensive gynecologic endoscopic privileging program at an urban teaching hospital and evaluate its effect on complication rates. STUDY DESIGN: In 1996, a gynecologic endoscopy privileging program was instituted. Initially, experienced surgeons were invited to apply for advanced privileges based on submission of a case list. Afterwards, new applications were approved by proctorship. Since 1995, charts have been reviewed using the following indicators; operating time, estimated blood loss, length of stay, readmission, diagnosis of cancer, reexploration and admission for hysteroscopic fluid overload. Cases were also independently identified when a major vascular or visceral injury occurred. RESULTS: Among the 3,880 gynecologic endoscopic procedures performed during the review period, 2,702 medical records were randomly screened. Following institution of the program, there was no change noted in rates of hysteroscopic fluid overload, readmission, reexploration or unrecognized diagnosis of cancer. However, a decrease was noted in excess blood loss (odds ratio [OR] 0.6, 90% confidence interval [CI] 0.4, 0.9) and operating time greater than four hours (OR 0.6, CI 0.4, 0.9). Length of hospital stay was also reduced in the year following implementation of the privileging process (OR 0.2, CI 0.1, 0.3). Fifty-four cases of visceral or major vascular injury occurred during the three-year period. The risk of visceral injury revealed a trend from 1.9% to 1.0% after institution of the privileging process (OR 0.5, CI 0.3, 1.0). CONCLUSION: Establishment of a comprehensive gynecologic endoscopic hospital privileging program was associated with a reduction in rates of excess blood loss and operating times and a decreasing trend in visceral injuries.
Mammalian spermatozoal mRNAs: tools for the functional analysis of male gametes.
Mammalian spermatogenesis reflects a dynamic partnership between somatic genes which display altered expression patterns within the testes and germ cell specific genes expressed solely during male gametogenesis. Among the latter include the haploid-specific transition proteins and protamines which facilitate the molecular restructuring of the chromatin during the terminal differentiation of the spermatid nucleus. Previously, we have shown that the human protamines PRM1, PRM2 and transition protein TNP2 transcripts persist in mature spermatozoa subsequent to their functional role during spermiogenesis. We now demonstrate the conserved presence of these same spermatozoal mRNAs in mouse. While the basis for the persistence of these haploid-specific transcripts remains poorly defined, the results presented firmly establish that the presence of mRNA in mammalian spermatozoa is a general phenomenon. The potential use of these transcripts as a tool for investigating molecular pathologies is discussed.
Mononuclear phagocytes mediate blood-brain barrier compromise and neuronal injury during HIV-1-associated dementia.
The neuropathogenesis of HIV-1 infection revolves around the production of secretory factors from immune-activated brain mononuclear phagocytes (MP). MP-secreted chemokines may play several roles in HIV-1 encephalitis (HIVE). These can promote macrophage brain infiltration, blood-brain barrier (BBB) and neuronal dysfunction during HIV-1-associated dementia. We investigate how HIV-1-infected MP regulates the production of chemokines and how they influence HIV-1 neuropathogenesis. We demonstrate that HIV-1-infected and immune-activated MP (for example, microglia) and astrocytes produce beta-chemokines in abundance, as shown in both laboratory assays and within infected brain tissue. HIV-1-infected microglia significantly modulate monocyte migration in a BBB model system and in brains of SCID mice with HIVE. HIV-1-infected MP down-regulate tight junction protein and special polarized transport systems on brain microvascular endothelial cells as shown in human autopsy brain tissue and in SCID mice with HIVE. Chemokines can damage neurons directly. Toxicity caused by binding of stromal-derived factor-1alpha to its receptor on neurons exemplifies such mechanism. In toto, these works underscore the diverse roles of chemokines in HIV-1 neuropathogenesis and lay the foundation for future therapeutic interventions.
To crush or not to crush? What to consider before giving medications to a patient with a tube or who has trouble swallowing.
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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.
Interviews with advanced practice nurses: a day in the life. Interview by Sherry L. Child.
The role of the advanced practice nurse in nephrology is evolving rapidly. The following questions and role descriptions were posted on the ANNAlink Advanced Practice ListServe. The dialogue is just beginning--stay tuned! Stay informed and connect to advance your practice!
Report from the XIII International AIDS Conference. Psychosocial issues of the HIV pandemic in Africa.
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