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Hospital Administration↗
Biomedical subjects
C R Miller
Publications and source records attributed to C R Miller.
Pediatric aspects of AIDS.
Children comprise only 2% of patients with AIDS in the United States, and this article considers the vast array of clinical and radiographic manifestations that may be seen in this patient population. Particular attention is paid to ways in which the disease in children differs from that in the adult population.
AIDS-Related Opportunistic Infections↗
Effect of liposomal composition on photoactivated liposome fusion.
Bennett and O'Brien [(1995) Biochemistry 34, 3102] showed that the ultraviolet light exposure of two-component large unilamellar liposomes (LUV) composed of a 3:1 molar mixture of dioleoylphosphatidylethanolamine (DOPE) and 1,2-bis[10-(2'-hexadienoyloxy)decanoyl]-sn-glycero-3-phosphatidyl- choline (bis-SorbPC) facilitated liposome fusion. The rate and extent of liposome fusion was dependent on the extent of photopolymerization, the temperature, and the pH. Examination of the temperature dependence of fusion of photolyzed and unphotolyzed liposomes demonstrated that an enhancement of the rate of fusion occurred in the temperature range associated with the initial appearance of precursors to the inverted cubic (QII) phase [Barry et al. (1992) Biochemistry 31, 10114]. Here, the effect of the molar lipid ratio of the DOPE/bis-SorbPC liposomes on the temperature for the onset of fusion, i.e. the critical fusion temperature, was characterized by changing the relative amounts of unreactive polymorphic lipid and reactive lamellar lipid. In each case, photopolymerization of bis-SorbPC lowered the critical fusion temperature by ca. 15-20 degrees C. The photoreaction of the bis-SorbPC-containing LUV yields cross-linked poly-SorbPC, enhancing the lateral separation of the DOPE and the polylipid and causing isothermal induction of liposome fusion by lowering the temperature for the onset of fusion. Evidence is presented to support the hypothesis that the critical temperature for fusion of two LUV populations depends on the molar ratio of the monomeric lipids in heterodimers of the two LUV. This analysis indicates that the photopolymerization of appropriately designed LUV can decrease the critical fusion temperature from above to below 37 degrees C.
4-Chloro-7-nitrobenzofurazan↗
Mathematical model for chemically induced lipid peroxidation in precision-cut liver slices: computer simulation and experimental calibration.
A biologically based pharmacodynamic (BBPD) model was developed in order to describe and simulate chemically induced lipid peroxidation in precision cut mouse liver slices. The model was written in Advanced Continuous Simulation Language (ACSL) and simulations were performed using SIMUSOLV software on a VAX/VMS mainframe computer. The BBPD model simulated formation of lipid hydroperoxides and thiobarbituric acid reactive substances (TBARS) over time as a function of the amounts of cytochrome P450 (CYP)-activated chemical inducer and active antioxidants. The rate of peroxidation was controlled by lipid peroxidizability, destruction of CYP, autooxidation, and activity of glutathione peroxidase. The BBPD model was initially parameterized with the literature data for TBARS formation during lipid peroxidation, reported for rat liver slices induced with bromotrichloromethane and tert-butyl hydroperoxide (TBOOH). Then, the biochemical parameters were adjusted to reflect the physiology of the mouse liver, and the BBPD model was used to simulate TBARS formation during lipid peroxidation in precision cut mouse liver slices induced with TBOOH. The BBPD model predictions were in agreement with the experimental data.
Animals↗
Resolution of Budd-Chiari syndrome following bone marrow transplantation for paroxysmal nocturnal haemoglobinuria.
Thrombosis of the hepatic veins (Budd-Chiari syndrome) is a life-threatening thrombotic complication which can occur in patients with paroxysmal nocturnal haemoglobinuria (PNH). Despite aggressive medical and surgical therapy, mortality from Budd-Chiari syndrome remains high. We report a boy with PNH who developed Budd-Chiari syndrome and underwent syngeneic bone marrow transplantation (BMT). Now, 3 years following BMT, he has had dramatic clinical and radiographic evidence of resolution of the thrombosis. We suggest that BMT for PNH can successfully correct life-threatening thrombosis in patients with PNH.
Bone Marrow Transplantation↗
Renal cell carcinoma after therapy for neuroblastoma.
OBJECTIVE: An unfortunate consequence of increased success in childhood cancer survival rates is the increase in the number of secondary malignant neoplasms after therapy for the initial lesion. Renal cell carcinoma can occur as a secondary malignant neoplasm after therapy for neuroblastoma and may become more common as more patients with treated neuroblastomas survive into adulthood. We studied one case and reviewed four cases of secondary renal cell carcinoma to determine if the relationship between these two neoplasms is significant. CONCLUSION: An awareness of the association between these two neoplasms is important in the diagnostic follow-up of neuroblastoma so that secondary renal cell carcinoma is not confused with recurrence of primary disease.
Carcinoma, Renal Cell↗
Efficient delivery of triplex forming oligonucleotides to tumor cells by adenovirus-polylysine complexes.
Oligonucleotides (ODNs) show great promise in their ability to specifically inhibit single gene expression but must cross the cell membrane, escape the endosomal vesicle, and possibly traverse the nuclear membrane to arrive at their intracellular target molecules. In an attempt to improve the delivery of phosphodiester triplex forming ODNs to malignant cells, we have constructed adenovirus-polylysine (AdpL)-ODN complexes designed to take advantage of the receptor mediated endocytosis of adenoviruses to transfer the ODNs to the cell nucleus. Treatment of several different types of tumor cells in culture by AdpL-ODN complex resulted in superior uptake and persistence of the ODNs compared to both free ODN and cationic lipid-ODN complexes. Nuclear uptake peaks at 4 h and intact ODN persists in the nucleus with a half-life of 12 h. ODN concentrations of 20-70 microM are achieved at 24 h in all monolayer cell lines evaluated to date. ODNs are detected in 50-100% of the total cell population by immunohistochemistry with apparent uptake into vesicles and nuclear localization. Luciferase expression of a co-delivered reporter plasmid suggests that these ODNs are free in the nucleus. AdpL-ODN complexes will provide a valuable tool for delivering unmodified ODNs to the nucleus of malignant cells.
Adenoviruses, Human↗
Anaplastic renal cell carcinoma following neuroblastoma.
Renal cell carcinoma is unusual in children. We report a case of anaplastic renal cell carcinoma arising in a 7-year-old girl following treatment for Stage III neuroblastoma. The renal cell carcinoma has unusual histologic and ultrastructural features, which are discussed. The case is further unusual in that few children with advanced stage neuroblastoma survive long enough to develop second malignant neoplasms.
Anaplasia↗
Spectrum of chest radiographic abnormalities in children with AIDS and Pneumocystis carinii pneumonia.
This report aims to provide a description of the spectrum of radiographic findings in children with AIDS and Pneumocystis carinii pneumonia (PCP). The chest radiographs of all children with perinatally transmitted HIV infection who had PCP were reviewed. Thirty-eight episodes of PCP were noted in 32 children. The age range was 2-17 months. The radiographic findings were characterized as to pattern, severity, presence of pulmonary air cyst, thoracic air leak, thoracic lymphadenopathy, and pleural effusion. The initial distribution of disease was as follows: diffuse (n = 20), patchy (n = 12), focal (n = 4), normal (n = 2). In nearly one-third of children parenchymal abnormalities were mild enough that most normal lung markings were visible. During the course of the illness pneumothorax was noted in eight cases, pulmonary air cyst in five, and pneumomediastinum in one. Pleural effusions were noted in three (5%) cases. Thoracic lymphadenopathy was not observed in any case. The authors concluded that the initial chest radiographic appearance of PCP in children with AIDS is variable. The initial chest radiograph may be normal. The distribution was patchy or focal in nearly one-half of all cases with parenchymal abnormalities. Pulmonary air cysts or thoracic air leaks were noted during the course of the illness in approximately one-third of all cases.
AIDS-Related Opportunistic Infections↗
Effects of dietary virginiamycin on performance and liver abscess incidence in feedlot cattle.
The effects of dietary virginiamycin level on performance and liver abscesses in feedlot cattle were evaluated in seven dose-response studies. Steers and heifers were fed finishing diets ranging in energy content from 1.34 to 1.51 Mcal of NEg/kg of DM. In all studies, virginiamycin added to the diet improved average daily gain and(or) feed conversion, with no substantial effect on dry matter intake. Pooled analyses of four studies providing virginiamycin at 11.0, 19.3, and 27.6 mg/kg of DM in the complete diet indicated that growth and feed conversion were linearly improved (P < .05); feeding 19.3 mg/kg improved these measurements by 3.0 and 3.8%, respectively. Overall incidence (score 0 vs score 1, 2, and 3) and severity (score 0, 1, and 2 vs score 3) of liver abscesses were reduced (P < .01) by feeding virginiamycin at either 19.3 or 27.6 mg/kg. Linear plateau modeling indicated that the effective dose range for virginiamycin in feedlot diets (DM basis) was 19.3 to 27.3 mg/kg for increasing average daily gain, 13.2 to 19.3 mg/kg for improving feed conversion, and 16.5 to 19.3 mg/kg for reducing liver abscess incidence.
Animals↗
Creative coping: a cognitive-behavioral group for borderline personality disorder.
Patients with borderline personality disorder (BPD) pose major therapeutic challenges to mental health professionals. Effective and practical treatment of the patient with BPD is needed in short-term inpatient settings, and psychiatric nurses are in a unique position to implement innovative treatment strategies for the borderline patient. The Creative Coping Group is a practice model designed by psychiatric nurses for patients with BPD, using a cognitive-behavioral framework. It is a group therapy intervention based on Linehan's Dialectical Behavior Therapy (DBT) that addresses the ineffective coping of patients with BPD that results in chronic suicidal behavior. Linehan's framework focuses on deficits in emotional control, interpersonal effectiveness, and distress tolerance. The objective of the group sessions is to foster insight and awareness into symptoms, feelings, and behaviors through psychoeducation, group exercises, discussion, and homework assignments.
Adaptation, Psychological↗
Pustular psoriasis with chronic recurrent multifocal osteomyelitis and spontaneous fractures.
Chronic recurrent multifocal osteomyelitis is rarely associated with pustular psoriasis in children. We describe a child with severe pustular psoriasis in whom multiple fractures, bone deformities, and severe growth failure from chronic recurrent multifocal osteomyelitis developed. The recurrent fractures led to an incorrect assumption of child abuse. Both the bone disease and pustular psoriasis responded to treatment with etretinate.
Adolescent↗
Disseminated histoplasmosis in chronic mucocutaneous candidiasis.
Chronic mucocutaneous candidiasis (CMC) is rarely associated with disseminated Candida, but is often associated with systemic infection secondary to other organisms [1]. A 6-year-old with CMC and disseminated histoplasmosis is presented here.
Candidiasis, Chronic Mucocutaneous↗
CYP1A1 mRNA levels as a human exposure biomarker: use of quantitative polymerase chain reaction to measure CYP1A1 expression in human peripheral blood lymphocytes.
Accurate human risk assessment requires sensitive methods to evaluate dose-response relationships, especially following low level exposures. We have developed a reverse transcriptase polymerase chain reaction (RT-PCR) method to quantitative cytochrome P450-1A1 (CYP1A1) mRNA levels in human blood lymphocytes. Many polycyclic aromatic hydrocarbons (PAH) such as benzo[a]pyrene, and chlorinated PAH such as polychlorinated dibenzodioxins, dibenzofurans and biphenyls induce CYP1A1 expression through activation of an endogenous protein, the Ah receptor. Using a quantitative competitive RT-PCR method that included a synthetic internal standard we determined copy numbers of CYP1A1 mRNA in resting as well as mitogen-stimulated human blood lymphocytes. In mitogen-stimulated human blood lymphocytes assay variation was approximately 10% for measurement of this low expression gene and mRNA levels correlated well with ethoxyresorufin-O-deethylase (EROD) activity. The expression of mRNA was induced 20-fold upon culturing human lymphocytes with 10 nM TCDD. In nonstimulated, uninduced lymphocytes CYP1A1 levels are extremely low (1000 copies mRNA/10(4) cells) and cannot be measured by EROD activity. Studies of CYP1A1 mRNA expression in chemically-exposed populations are in progress.
Base Sequence↗
Genetic monitoring of human polymorphic cancer susceptibility genes by polymerase chain reaction: application to glutathione transferase mu.
Several genes involved in the metabolism of carcinogens have been found to be polymorphic in human populations and are associated with increased risk of cancer at some sites. This study focuses on the polymorphic enzyme glutathione transferase mu (GT mu). Smokers with low lymphocyte GT mu activity are at an approximately 2-fold higher risk for lung cancer and an approximately 3-fold higher risk for stomach and colon adenocarcinomas. Recent cloning and sequencing of the GST1 gene has allowed the development of convenient genotyping methods based on restriction fragment length polymorphisms (RFLP) or the polymerase chain reaction (PCR). The GST1 polymorphism has been shown to be a deletion of the gene locus. To detect the presence or absence of the gene we amplified exons 4-5 and/or exons 6-7 of the GST1 gene by PCR. PCR amplification produced bands of 215-bp or 273-bp from individuals with one or two copies of the GST1 allele and no band if the individual was homozygously deleted (0/0). In the exon 6-7 PCR, we co-amplified a 268-bp portion of the beta-globin gene as an internal reference standard for quantitative analysis of product yield. This allowed homozygote individuals (+/+) to be distinguished from heterozygotes (+/0). We have compared the GST1 genotype to lymphocyte GT mu activity measured on trans-stilbene oxide (TSO) in the lymphocytes of 45 individuals. Low GT mu activity (< 67 pmole/min/10(7) cells) was strongly associated (24/24) with the GST1 0/0 genotype. With the exception of one individual, activities greater than 67 pmole/min/10(7) were associated with the presence of the GST1 allele (20/21). Individuals with the highest GT-TSO activity were found to be homozygous for GST1. (+/+), while heterozygotes (+/0) generally had lower activity, suggesting a gene dosage effect in lymphocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
Gene Deletion↗
Non-metallothionein-bound cadmium in the pathogenesis of cadmium nephrotoxicity in the rat.
Male rats were injected SC with 0.6 mg Cd/kg/day for 5 days per week for 2, 4, 6, and 8 weeks. Liver and kidney were examined morphologically and analyzed for metallothionein, cadmium, zinc, and copper. Morphologic changes were found in kidney but not in liver. The earliest ultrastructural change consisted of myelin figures in vacuoles in cytoplasm of proximal tubular lining cells reflecting degeneration of membranes. This change occurred after 4 weeks with 801 +/- 25 nmol/g (89.9 micrograms/g) total kidney cadmium or 390 nmol/g (43.7 micrograms/g) of cadmium not bound to metallothionein. Similar changes were observed after 6 weeks but after 8 weeks pathological changes consisted of focal cellular necrosis and interstitial fibrosis. Other ultrastructural changes included altered mitochondria and increased numbers of microbodies. Renal cadmium after 8 weeks exposure was 1827 +/- 48 nmol/g (215.3 +/- 5.8 micrograms/g) or 628 nmol/g (70.2 micrograms/g) of cadmium not bound to metallothionein. Total cadmium was higher in liver than in kidney but partitioning between bound and nonbound cadmium differed in the two organs. The fraction not bound to metallothionein increased with time of exposure in both liver and kidney. However, total cadmium in the liver did not exceed potentially available binding sites of metallothionein, whereas total cadmium did exceed potentially available binding sites of metallothionein in the kidney where pathologic changes occurred. The results indicated that degeneration of cellular membranes is an early cellular effect of cadmium exposure followed later by toxicity to organelles, cellular necrosis, and interstitial fibrosis. Cadmium-induced cellular toxicity is more directly related to the fraction of cadmium in the kidney that is not bound to metallothionein than is total cadmium per se.
Animals↗
Arthrodesis of the scapulohumeral joint in a miniature horse.
Scapulohumeral arthrodesis was performed successfully as treatment for severe degenerative arthritis in a 62-kg miniature horse. Using an approach similar to that used for a dog, this horse's scapulohumeral joint was opened, the cartilage was removed, and the site was stabilized, using an 11-hole narrow dynamic compression plate. Fusion was uncomplicated. The stallion became a successful pasture-breeding animal.
Animals↗
Effect of calcium entry blockers on blood pressure and vasoconstrictor responses to alpha-1 adrenoceptor stimulation in conscious spontaneously hypertensive rats.
In order to investigate whether vascular alpha-1 adrenoceptor antagonism plays a role in the antihypertensive effect of verapamil, tiapamil, and nifedipine, we studied their potencies to inhibit K(+)-induced 45Ca2+ influx in rat isolated aorta and [3H]prazosin binding in rat brain membranes in vitro as well as their antihypertensive effect and functional alpha-1 adrenoceptor blockade in conscious spontaneously hypertensive rats (SHR) in vivo. Tiapamil proved 70 times less potent than verapamil in inhibiting calcium influx, but was equipotent in displacing [3H]prazosin. Nifedipine proved 10 times more potent than verapamil as calcium channel blocker but displayed negligible affinity for alpha-1 adrenoceptors in vitro. In conscious SHR, the three calcium channel blockers dose-dependently reduced mean arterial pressure after oral administration. Only at maximal anti-hypertensive doses, the increases in diastolic pressure to intravenous injection of the selective alpha-1 adrenoceptor agonist cirazoline were temporarily suppressed by nifedipine, verapamil, and tiapamil. No relationship existed between the relative potencies as calcium channel blocker and affinities for alpha-1 adrenoceptor binding sites in vitro with functional vascular alpha-1 adrenoceptor blockade in vivo. The data do not support the hypothesis that vascular alpha-1 adrenoceptor blockade plays a significant role in the anti-hypertensive effect of verapamil and related calcium channel blockers.
Administration, Oral↗