Search PubMed⌕ Search

Biomedical subjects

J Miller

Publications and source records attributed to J Miller.

At least 541 records · Page 30Linked to original sources

The influence of dose, dose-rate and particle fragmentation on cataract induction by energetic iron ions.

Because activities in space necessarily involve chronic exposure to a heterogeneous charged particle radiation field it is important to assess the influence of dose-rate and the possible modulating role of heavy particle fragmentation on biological systems. Using the well-studied cataract model, mice were exposed to plateau 600 MeV/amu 56Fe ions either as acute or fractionated exposures at total doses of 5 - 504 cGy. Additional groups of mice received 20, 360 and 504 cGy behind 50 mm of polyethylene, which simulates body shielding. The reference radiation consisted of 60Co gamma radiation. The animals were examined by slit lamp biomicroscopy over their three year life spans. In accordance with our previous observations with heavy particles, the cataractogenic potential of the 600 MeV/amu 56Fe ions was greater than for low-LET radiation and increased with decreasing dose relative to gamma-rays. Fractionation of a given dose of 56Fe ions did not reduce the cataractogenicity of the radiation compared to the acute regimen. Fragmentation of the beam in the polyethylene did not alter the cataractotoxicity of the ions, either when administered singly or in fractions.

Animals↗

Ground-based simulations of galactic cosmic ray fragmentation and transport.

Since mean free paths for nuclear fragmentation are of the order of the ranges of primary Galactic Cosmic Ray (GCR) nuclei, determination of the radiation field produced by successive fragmentations of nuclei in material and tissue is essential to accurate assessment of GCR radiation risk to humans on long-duration missions outside the geomagnetosphere. We describe some recent measurements made at the Bevalac of heavy ion transport through materials, with representative results and examples of how they may be applied to aspects of the space radiation problem, including efforts to devise analytical tools for predicting biological effects and for designing spacecraft shielding.

Computer Simulation↗

A strategy for trauma debriefing after railway suicides.

Following an increase in the incidence of railway suicide from an average of four events a year up to 1989 to 12 in 1990 an initiative was developed between the District Department of Clinical and Community Psychology, Exeter Health Authority and British Rail, Western Region. Traincrew leaders and management had become increasingly aware of the severity of the short- and long-term effects on drivers of experiencing a suicide. Although a management strategy had been developed over time to deal with what had been a rare phenomenon it was clear that such a dramatic increase in suicides warranted a more professional approach to debriefing and trauma counselling. This paper describes the strategies adopted by psychologists in developing an understanding of the stresses of experiencing suicides and other major incidents. The outcome of small group sessions with affected drivers is outlined. An account of the strategy developed through workshops with traincrew leaders is detailed and a three-stage debriefing (shock, search, adjustment) and follow-up protocol is discussed. This process is proposed for adoption as normal procedure following suicides or similar traumas for drivers and line managers.

Adaptation, Psychological↗

MHC class II antigen processing: biology of invariant chain.

The invariant chain (Ii) has been shown to play a critical role in the assembly, intracellular transport and function of MHC class II molecules. Recent studies suggest that these distinct activities can in many cases be attributed to distinct isoforms of Ii or to specific regions within it. Thus, regulation of Ii synthesis, post-transcriptional events, and post-translational modification has the potential to dramatically modulate immune responses.

Animals↗

A modular solid state detector for measuring high energy heavy ion fragmentation near the beam axis.

A multi-element solid state detector has been designed to measure fluences of fragments produced near the beam axis by high energy heavy ion beams in thick targets. The detector is compact and modular, so as to be readily reconfigured according to the range of fragment charges and energies to be measured. Preamplifier gain settings and detector calibrations are adjustable remotely under computer control. We describe the central detector, its associated detectors and electronics, triggering scheme, data acquisition and particle identification techniques, illustrated by data taken with 600 MeV/u 56Fe beams and thick polyethylene targets at the LBL Bevalac. The applications of this work to space radiation protection are discussed.

Algorithms↗

Effects of morphine and pancuronium on lung volume and oxygenation in premature infants with hyaline membrane disease.

To determine the effect of analgesia and paralysis on lung volume and oxygenation in premature infants supported by mechanical ventilation because of hyaline membrane disease, functional residual capacity (FRC), and arterial/alveolar oxygen tension ratio were measured in nine premature infants with hyaline membrane disease before and after the administration of morphine sulfate and pancuronium bromide. Without a change of positive end-expiratory pressure, ventilator rate and peak inspiratory pressure were increased before the first set of measurements to minimize the contribution of the infants' own respiratory effort to total ventilation. These ventilator settings were then held constant (except fraction of inspired oxygen) before and after the administration of the drugs. The FRC was measured with a multiple-breath N2 washout technique by means of whole-body plethysmography to measure airway flow. The FRC and the ratio of arterial to alveolar oxygen tension decreased in seven of nine patients after treatment with morphine and pancuronium. The decrease in FRC for all patients was significant (2.4 +/- 2.9 ml/kg; p < 0.05), and a significant correlation was demonstrated between the change in the arterial/alveolar oxygen tension ratio and the change in FRC (r = 0.82; p < 0.01). Gestational age, birth weight, postnatal age, severity of lung disease, and time after the administration of morphine and pancuronium were not significantly correlated with the change in FRC. We believe that a decrease in oxygenation caused by alveolar derecruitment occurred even though the ventilator settings had been increased before the first set of measurements. The decrease in FRC in these infants, who are thought to have alveolar instability because of surfactant deficiency, may have resulted from the loss of expiratory braking mechanisms. We conclude that analgesia and paralysis should be used with caution under these circumstances.

Functional Residual Capacity↗

Oral conjugated estrogen therapy for treatment of hemorrhagic cystitis.

We report 7 cases of severe hemorrhagic cystitis that required repeated transfusions, surgical intervention and oral conjugated estrogens. Of these 7 cases hematuria resolved completely in 5 during estrogen therapy and decreased sufficiently in 1 to preclude further transfusion. We found conjugated estrogens to be an effective, simple, inexpensive, well tolerated and readily available treatment for hemorrhagic cystitis.

Administration, Oral↗

Failure of intravenous low dose midazolam to influence memory recall in drug paralysed post-operative patients sedated with papaveretum.

Sedation of ventilated patients in the Intensive Care Unit generates a tension between adequate sedation to maintain comfort and ease of ventilation and over sedation with undesirable prolongation of ventilation and delays in discharge. Studies in animals suggest very low dose midazolam, but not higher doses, potentiate the sedative effects of opiates. We undertook a trial of opiate sedation versus opiate sedation plus low dose midazolam (1 mg/hour) to determine whether a similar effect could be demonstrated in man. Although ventilator time and the duration of admission to Intensive Care was not prolonged by the addition of midazolam, we were unable to demonstrate any statistically significant benefit with regard to memory recall.

Procedural Sedation↗

Municipal drinking water and cryptosporidiosis among persons with AIDS in Los Angeles County.

To assess unfiltered drinking water as a source of cryptosporidium infection in patients with the acquired immunodeficiency syndrome (AIDS) the prevalence of cryptosporidiosis among persons with AIDS in Los Angeles County was assessed by water service area. One water distributor, serving approximately 60% of the county's residents (area B), has consistently employed filtration. The other company, which serves the remainder of the county (area A), did not institute filtration until mid-December 1986. This difference provided a 'natural experiment' in which to assess the effect of municipal water filtration on the level of cryptosporidiosis among persons with AIDS. The prevalence of cryptosporidiosis among AIDS patients was compared for the two water service areas for the time period (1983-6) preceding the implementation of filtration in area A. From 1983 to 1986 the age-standardized prevalence of cryptosporidiosis among AIDS patients was 32% lower in area A (4.2%), which received unfiltered water, than in area B (6.2%). Following addition of filtration in area A, the prevalence of cryptosporidiosis among AIDS patients decreased by 20%; however, a decline, of 47%, was also observed in area B. The similar baseline levels of cryptosporidiosis and the corresponding post-filtration decline in both areas suggest that filtration had no effect on levels of cryptosporidiosis among persons with AIDS. Thus it does not appear that municipal drinking water is an important risk factor for cryptosporidiosis in AIDS patients residing in Los Angeles County.

AIDS-Related Opportunistic Infections↗

A violation of pure insertion: mental rotation and choice reaction time.

Six experiments tested the assumption that the mental rotation process is purely inserted into a mirror-normal discrimination task. In Experiment 1, subjects took significantly longer to respond to upright characters in blocks containing rotated stimuli than in blocks containing only upright stimuli. Experiments 2 and 3 showed that this "rotational uncertainty" effect was not caused by the need to determine stimulus orientation, and Experiment 4 showed that it was independent of the visual quality of the stimulus. Experiment 5 showed that the effect was greatly reduced when subjects performed a go-no-go task rather than choice reaction time (RT), and Experiment 6 showed that it was independent of the complexity of the response required in the choice task. The results suggest that response selection in a choice RT mirror-normal discrimination task is altered when mental rotation is added, violating the assumption of pure insertion.

Choice Behavior↗

Effects of truncation on reaction time analysis.

Many reaction time (RT) researchers truncate their data sets, excluding as spurious all RTs falling outside a prespecified range. Such truncation can introduce bias because extreme but valid RTs may be excluded. This article examines biasing effects of truncation under various assumptions about the underlying distributions of valid and spurious RTs. For the mean, median, standard deviation, and skewness of RT, truncation bias is larger than some often-studied experimental effects. Truncation can also seriously distort linear relations between RT and an independent variable, additive RT patterns in factorial designs, and hazard functions, but it has little effect on statistical power. The authors report a promising maximum likelihood procedure for estimating properties of an untruncated distribution from a truncated sample and present in an appendix a set of procedures to control for truncation biases when testing hypotheses.

Bias↗

The impact of hepatitis C virus infection on renal allograft recipients.

A second generation hepatitis C virus recombinant immunoblot assay (RIBA) was used to screen stored perioperative serum from 641 renal allograft recipients. One hundred and nine (17%) were anti-HCV positive at the time of transplant. RIBA positivity was found to be an independent predictor of post-transplant liver disease in a logistic regression model (P < 0.05). Moreover, RIBA positive patients were at greater risk for infectious events (P = 0.03) and rejection episodes (P = 0.002). The cumulative dose of antilymphoblast globulin administered as induction therapy was an independent predictor of post-transplant liver disease in a dose response relationship. Qualitative PCR showed that 74% of the perioperative RIBA positive patients had detectable HCV RNA in a current serum sample. Further, quantitative HCV RNA analysis with a competitive template PCR and HCV strain identification by restriction fragment length polymorphism demonstrated a large range of HCV RNA copies/ml of serum and three different HCV strains (BK, Hutch and HCV-1). Neither quantity of HCV RNA nor strain type correlated with abnormal transaminases post-transplant. As yet, there has not been an effect of anti-HCV status on actuarial patient and graft survival. This study suggests that anti-HCV is not a contraindication to renal transplantation; however, we would recommend that the pre-transplant evaluation of the anti-HCV positive patient include a liver biopsy to properly stage the disease. Close post-transplant follow-up is required in view of the increased risk for infection and rejection.

Adult↗

Treatment with intralesional granulocyte instillations and interferon-gamma for a patient with chronic granulomatous disease and multiple hepatic abscesses.

We present the case of a 16-year-old girl with p22-deficient chronic granulomatous disease in whom multiple hepatic abscesses secondary to Staphylococcus aureus infection developed. Infection persisted despite extensive surgery and aggressive antibiotic therapy. Conventional intravenous granulocyte transfusions were not tolerated because of the development of alloantibodies to HLA. Treatment with interferon-gamma and intralesional granulocyte infusions was associated with dramatic clinical and radiographic improvement. No morbidity was associated with this therapy. To our knowledge, this is the first report of treatment with intralesional granulocyte instillations. Intralesional granulocyte instillation in association with interferon-gamma administration may result in clinical improvement in the conditions of patients with chronic granulomatous disease and hepatic abscesses for whom conventional therapy has failed.

Adolescent↗

Minimum alveolar concentration of isoflurane for tracheal extubation in deeply anesthetized children.

BACKGROUND: The end-tidal anesthetic gas concentration required to prevent the anesthetized patient from coughing or moving during or immediately after tracheal extubation is not known. METHODS: We studied 19 nonpremedicated children between 4 and 9 yr of age (5.5 +/- 1.8, mean +/- standard deviation), ASA physical status 1 or 2, undergoing muscle surgery for correction of strabismus. General anesthesia was induced by a mask using halothane, nitrous oxide, and oxygen, and the trachea was intubated. Anesthesia was maintained with either isoflurane, nitrous oxide, and oxygen (12 patients), or isoflurane, air, and oxygen (7 patients). However, nitrous oxide was discontinued before the end of surgery. At the end of surgery, a predetermined end-tidal isoflurane concentration was achieved, a steady state maintained for at least 10 min, and the trachea was extubated. In patients who coughed or bucked on the endotracheal tube during suctioning of the stomach or pharynx, or who moved or coughed within 1 min of tracheal extubation, or who developed breath-holding or laryngospasm after tracheal extubation, extubation was considered as unsatisfactory. Results were plotted as satisfactory or unsatisfactory extubation versus end-tidal isoflurane concentration. End-tidal concentration of isoflurane at which tracheal extubation was accomplished in 50% of patients satisfactorily was estimated by probit analysis. RESULTS: The minimum alveolar concentration of isoflurane at which 50% of patients had satisfactory tracheal extubation was found to be 1.27% (standard error +/- 0.04%). CONCLUSIONS: In 50% of anesthetized children age 4-9 yr tracheal extubation may be accomplished without coughing or moving at 1.27% end-tidal isoflurane concentration.

Anesthesia, General↗

The oligosaccharide composition of human milk: temporal and individual variations in monosaccharide components.

Oligosaccharides are an important component of human milk, but little is known about variations in their composition. The aim of this study was to determine the temporal and inter-individual variations in carbohydrate composition of human milk during the first 3 months of lactation. Serial milk samples of 10 mothers (eight full-term and two preterm births) were analyzed to determine the concentration of lactose and three monosaccharide components derived from the non-lactose carbohydrate: sialic acid, N-acetylglucosamine, and fucose. In full-term milk, sialic acid and N-acetylglucosamine were found to decrease significantly (p < 0.05) from weeks 1 to 13 postnatally. On average (mean +/- SD), sialic acid decreased by 71% (from 879 +/- 157 to 256 +/- 82 mg/L; p < 0.05) and N-acetylglucosamine by 56% (from 1,459 +/- 282 to 646 +/- 214 mg/L; p < 0.05), while fucose decreased by only 35% (from 660 +/- 192 to 432 +/- 180 mg/L; p > 0.05). On average, lactose concentration increased by 17% over the same period, from 55.4 +/- 4.2 g/L in week 1 to 64.9 +/- 2.3 g/L at 3 months. Preterm milk contained higher concentrations of each component, but temporal changes were similar to those seen in full-term milk. Apart from temporal changes, there were large inter-individual differences in oligosaccharide composition: fucose varied four-fold, sialic acid threefold, and N-acetylglucosamine two-fold among women at the same stage of lactation. The changes observed may simply reflect the aging of the cells responsible for milk secretion, but they are also consistent with a programmed adaptation of the milk composition to the needs of the infant.

Acetylglucosamine↗

Hepatitis C in liver transplantation: preliminary study of prognostic factors.

At the University of Miami liver transplantation for chronic liver disease in HCV-positive patients has shown good results, with a 92% patients survival rate (follow up 8 to 57 months, median 21). None the less, we found that a large number of patients are expected to develop serious histological graft damage and may need retransplantation, which may place a further strain on the already scarce donor resources. We have conducted a preliminary investigation on the importance of parameters which may correlate with the prognosis of HCV grafts. We found no impact of HLA match or typing. An interesting hypothesis, which deserves further investigation, is that some HCV strains could be more virulent than others and play a role as an independent risk factor. We have identified six strains among our patients and the BK serotype shows a trend to be associated with a worse outcome. We have found that patients developing and maintaining higher liver enzyme levels (ALT and GGT) after transplant and those with higher levels of viremia may be at risk to develop serious damage to their grafts.

Adolescent↗

The 58,000-dalton cellular inhibitor of the interferon-induced double-stranded RNA-activated protein kinase (PKR) is a member of the tetratricopeptide repeat family of proteins.

PKR is a serine/threonine protein kinase induced by interferon treatment and activated by double-stranded RNAs. As a result of activation, PKR becomes autophosphorylated and catalyzes phosphorylation of the alpha subunit of protein synthesis eukaryotic initiation factor 2 (eIF-2). While studying the regulation of PKR in virus-infected cells, we found that a cellular 58-kDa protein (P58) was recruited by influenza virus to downregulate PKR and thus avoid the kinase's deleterious effects on viral protein synthesis and replication. We now report on the cloning, sequencing, expression, and structural analysis of the P58 PKR inhibitor, a 504-amino-acid hydrophilic protein. P58, expressed as a histidine fusion protein in Escherichia coli, blocked both the autophosphorylation of PKR and phosphorylation of the alpha subunit of eIF-2. Western blot (immunoblot) analysis showed that P58 is present not only in bovine cells but also in human, monkey, and mouse cells, suggesting the protein is highly conserved. Computer analysis revealed that P58 contains regions of homology to the DnaJ family of proteins and a much lesser degree of similarity to the PKR natural substrate, eIF-2 alpha. Finally, P58 contains nine tandemly arranged 34-amino-acid repeats, demonstrating that the PKR inhibitor is a member of the tetratricopeptide repeat family of proteins, the only member identified thus far with a known biochemical function.

Amino Acid Sequence↗