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Biomedical subjects

D Miller

Publications and source records attributed to D Miller.

At least 91 records · Page 5Linked to original sources

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↗

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.

Antineoplastic Combined Chemotherapy Protocols↗

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.

Aortic Dissection↗

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.

Adult↗

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.

Aged↗

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.

Chicago↗

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.

Animals↗

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.

AIDS Dementia Complex↗