Biomedical subjects
M Miller
Publications and source records attributed to M Miller.
Inventory of Complicated Grief: a scale to measure maladaptive symptoms of loss.
Certain symptoms of grief have been shown (a) to be distinct from bereavement-related depression and anxiety, and (b) to predict long-term functional impairments. We termed these symptoms of "complicated grief" and developed the Inventory of Complicated Grief (ICG) to assess them. Data were derived from 97 conjugally bereaved elders who completed the ICG, along with other self-report scales measuring grief, depression, and background characteristics. Exploratory factor analyses indicated that the ICG measured a single underlying construct of complicated grief. High internal consistency and test-retest reliabilities were evidence of the ICG's reliability. The ICG total score's association with severity of depressive symptoms and a general measure of grief suggested a valid, yet distinct, assessment of emotional distress. Respondents with ICG scores > 25 were significantly more impaired in social, general, mental, and physical health functioning and in bodily pain than those with ICG scores < or = 25. Thus, the ICG, a scale with demonstrated internal consistency, and convergent and criterion validity, provides an easily administered assessment for symptoms of complicated grief.
The asymmetry of P+ in bacterial reaction centers revealed by circular dichroism spectroscopy.
The circular dichroism anisotropy, (AL-AR)/A, has been measured for the far-red absorption band of P+ in reaction centers of two purple bacteria (Rhodopseudomonas viridis and Rhodobacter sphaerides) and one green sulfur bacterium (Chlorobium tepidum). The anisotropy values for P960+ (Rps. virdis) at 1310 nm was found to be +(13 +/- 2) x 10(-4). The corresponding for P870+ (Rb. sphaeroides) at 1250 nm was +(11 +/- 1) x 10(-4), but for P840+ (C. tepdium) at 1160 nm the value was negative: -(27 +/- 2) x 10(-4). These results show that the configuration of the special pair in P840 is significantly different from the configuration in P870 and P960.
Effect of aggressive daunomycin therapy on survival in acute promyelocytic leukemia.
The Southwest Oncology Group analyzed outcome with cytotoxic chemotherapy for previously untreated acute myeloblastic leukemia (AML) from 1982 through 1986. Results with acute promyelocytic leukemia (APL) prompted comparison with patients from 1986 through 1991 and analysis of factors contributing to APL results. Patient and disease characteristics and treatment outcome were compared for all evaluable patients, with more detailed analysis of factors affecting APL treatment outcome. From 1982 through 1986, median survival and disease-free survival in 45 APL patients were 106 months and greater than 105 months, respectively, versus 6 and 14 months for 417 other AML patients. Such differences were not seen from 1986 through 1991. In the 141 APL patients from 1982 through 1991, after adjusting for significant patient and disease characteristics, higher daunomycin (DNR) doses during induction were significantly associated with higher complete remission rates (P < .0001), longer survival (P < .0001), and longer DFS (P < .0001). Cytosine arabinoside (Ara-C) induction dose, the inclusion of other chemotherapy agents in induction, postremission therapy (consolidation, maintenance, or bone marrow transplantation) other than DNR, APL subtype, and patient age did not appear to significantly affect outcome of APL, except for a significant detrimental effect of high-dose Ara-C in consolidation (P = .0042). Morphologic AML subtypes other than APL did not affect outcome. We conclude that high-dose DNR selectively increases survival in APL. This good survival is important for evaluation of combined all-trans retinoic acid (ATRA)/chemotherapy protocols and for planning future combinations of chemotherapy and ATRA. These results illustrate the need to individualize chemotherapy for subtypes of AML. Therapeutic response of APL is independent of age. Except for APL, morphologic subclassification of AML contributed little prognostic information.
Glomerulonephritis after human parvovirus infection in homozygous sickle-cell disease.
Glomerulonephritis with proteinuria of sufficient degree to manifest the nephrotic syndrome followed aplastic crises induced by human parvovirus (B19) in seven patients with homozygous sickle-cell disease, within 7 days in five patients and 6-7 weeks in two. Segmental proliferative glomerulonephritis was found in all four patients who underwent acute renal biopsies and focal segmental glomerulosclerosis was found in the fifth patient who had a biopsy 4 months later. One patient recovered completely, one died in chronic renal failure after 3 months, and the others had impaired creatinine clearance, four with continuing proteinuria.
Role of endothelin in the exercise intolerance of chronic heart failure.
In conclusion, plasma levels of the endothelial-derived vasoconstrictor endothelin-1 (but not those of other neurohormonal vasoconstrictor factors), measured during exercise correlated closely with objective variables of exercise capacity in patients with heart failure. These findings suggest that endothelin-1 may contribute to exercise intolerance in patients with heart failure, perhaps by limiting the ability of the peripheral vasculature to dilate during exercise.
Divergent reporting of coronary risk factors before coronary artery bypass surgery.
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Photooxidation of Trp-191 in cytochrome c peroxidase by ruthenium-cytochrome c derivatives.
A novel photoinduced electron-transfer reaction is reported in complexes between resting ferric state cytochrome c peroxidase (CcP) and several horse cytochrome c derivatives labeled at single lysine amino groups with [bis(bipyridine)](dicarboxybipyridine)ruthenium(II) (Ru-CC). Photoexcitation of Ru(II) in the 1:1 Ru-27-CC:CcP complex results in formation of a metal-to-ligand charge-transfer state, Ru(II*), which is a strong reducing agent and rapidly transfers an electron to the CC heme Fe(III) with rate constant k1 = 2.3 x 10(7) s-1. The resulting Ru(III) is a strong oxidizing agent with a redox potential of 1.3 V, and it oxidizes the indole ring of Trp-191 with rate constant k3 = 7 x 10(6) s-1. The cycle is completed by electron transfer from Fe(II) in CC to the Trp-191 radical in CcP with rate constant k4 = 6.1 x 10(4) s-1. The Ru group is located close to the interaction domain in the Ru-27-CC:CcP complex, allowing rapid electron transfer with both the heme in CC and Trp-191 in CcP. The electron-transfer reaction was not observed in CcP compound I, where Trp-191 is already oxidized to the radical, or in the W191F mutant, where the indole group is replaced with a phenyl group. The electron-transfer reaction was observed in CcP mutants modified at residues in the heme crevice, R48K, R48L, H52L, M230I, and M231I, but not in D235N which destabilizes the radical on Trp-191. Increasing the ionic strength results in an increase in the equilibrium dissociation constant K of the Ru-27-CC:CcP complex and an increase in the rate constant k5 for dissociation of the transient intermediate containing Fe(II) CC and the radical form of CcP. Both K and k5 were also increased significantly by the mutations D34N, E290N, and A193F involving residues located in the interaction domain of the crystalline complex between yeast CC and CcP [Pelletier & Kraut (1992) Science 258, 1748-1755]. This new method allows the study of the electron-transfer reaction between CC and the radical on Trp-191 in the complete absence of hydrogen peroxide, and it opens the possibility of measurements at low temperatures in frozen glasses or in crystals.
Measurement of Quasielastic 3He(p
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Lung tumor cells: a multivariate approach to cell classification using two-dimensional protein pattern.
High resolution two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) is a powerful research tool for the analytical separation of cellular proteins. The qualitative and quantitative pattern of polypeptides synthesized by a cell represents its phenotype and thus defines characteristics such as the morphology and the biological behavior of the cell. By analyzing and comparing the protein patterns of different cells it is possible to recognize the cell type and also to identify the most typical features of these cells. In applied pathology it is often difficult to identify the tissue of origin and the stage or grade of a neoplasia by cellular morphology analyzed by classical or immunostaining procedures. The protein pattern itself is the most characteristic feature of a cell and should therefore contribute to the identification of the cell type. For this reason we separated protein fractions originating from different lung tumor cell lines using 2-D PAGE and we compared the resulting patterns on a multivariate statistical level using correspondence analysis (CA) and ascendant hierarchical clustering (AHC). The results indicate that (i) protein patterns are highly typical for cells and that (ii) the comparison of the protein patterns of a set of interesting cell types allows the identification of potentially new marker proteins. 2-D PAGE is thus a unique and powerful tool for molecular cytology or histopathology, unveiling the protein expression level of tissues or cells.
Breaking the shackles of the genetic code: engineering retroviral proteases through total chemical synthesis.
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Monocyte adherence to the subendothelial basement membrane increases interleukin-8 gene expression and antigen release.
The emigration of peripheral blood monocytes into the interstitium allows for contact with a variety of surfaces which may provide signals important for monocyte function in both normal and inflammatory states. In the present study, we examined the effect of adherence to an endothelial cell-derived basement membrane and to collagen I, the major collagen of the interstitium, on monocyte release and gene expression of the potent chemotactic cytokine Interleukin-8 (IL-8). We further evaluated neutrophil chemotactic activity of the conditioned media containing antigenic IL-8 from monocytes adherent to these same surfaces. Elutriation-purified monocytes were adhered for 1 hour to plastic tissue culture wells either uncoated (PL) or coated with bovine serum albumin (BSA), collagen type I (C-I), or endothelial cell-derived basement membrane (BM). Following removal of nonadherent cells, monocytes were further incubated in a serum-free media for 18 hours in the presence or absence of lipopolysaccharide (IPS). Following 18 hrs of incubation there were significantly less monocytes remaining adherent to BM when compared to other surfaces tested. In the absence of LPS, adherent monocytes released significant amounts of IL-8 that was not surface specific. In the presence of LPS, monocytes adherent to BM released significantly more IL-8, when corrected for adherent cell number, than monocytes adherent to PL, BSA, or C-I. Conditioned media from adherent monocytes expressed IL-8 dependent neutrophil chemotactic activity that was not influenced by the surfaces tested. Northern blot analysis indicated greater induction for IL-8 mRNA by monocytes adhered to BM after 18 hrs in the presence of LPS. These results suggest that monocyte adherence to the subendothelial basement membrane provides a priming signal for the induction and secretion of the chemotactic cytokine IL-8 in response to inflammatory stimuli.
Intensive home-care surveillance prevents hospitalization and improves morbidity rates among elderly patients with severe congestive heart failure.
The purpose of this study was to examine the impact of intensive home-care surveillance on morbidity rates of elderly patients with severe congestive heart failure. Forty-two patients aged 78 +/- 8 years who had severe congestive heart failure (New York Heart Association functional classes III through IV, mean ejection fraction 27% +/- 6%), were examined at least once a week at home by internists from the district hospital and by a trained paramedical team. The year before entry to the home-care program was compared to the first year of home surveillance. The mean total hospitalization (hosp) rate was reduced from 3.2 +/- 1.5 hosp/yr to 1.2 +/- 1.6 hosp/yr and duration from 26 +/- 14 days/yr to 6 +/- 7 days/yr (p < 0.001 for both). Cardiovascular admissions decreased from 2.9 +/- 1.5 hosp/yr to 0.8 +/- 1.1 hosp/yr and duration from 23 +/- 13 days/yr to 4 +/- 4 days/yr (p < 0.001). The vital status (ability to perform daily activities, expressed in a 1 to 4 scale) was improved from 1.4 +/- 0.9 to 2.3 +/- 0.7 (p < 0.001). In conclusion, an intensive home-care program was associated with a marked decrease in the need for hospitalization and improved the functional status of elderly patients with severe congestive heart failure. Such a service might also have a cost-effective advantage and a major impact on health expenditure.
Australian healthcare: a smart card for a clever country.
In this paper we give an overview of smart card technology how a smart card could be used as a healthcare card and the benefits that would most likely result from doing so. The smart card memory can be zoned into different security levels. The top security zone may contain an individual's full medical history while the lowest security zone may contain the cardholders name and address. Access to the different zones depends on the level of security of the zone. The higher the security level the more restrictive the access method. Were smart cards adopted for the storage of medical histories it would change the form of medical information recorded, not merely convert paper files to electronic ones. Storage of an individual's medical history on a smart card raises important privacy issues. These privacy issues are discussed particularly as they relate to the Australian community.
Evaluation of three glutaraldehyde-based disinfectants used in endoscopy.
The European suspension test was applied to compare the in vitro activity of three glutaraldehyde-based disinfectants: a 1:10 dilution of a 10% glutaraldehyde solution containing 0.5% phenylphenol-0.1% amylphenol, a 2% acid glutaraldehyde solution, and a 2% alkaline glutaraldehyde solution. The microbicidal effect of the disinfectants was evaluated by counting surviving cells of three indicator microorganisms (Pseudomonas aeruginosa, Mycobacterium chelonae and phage f2) after exposure times of 5, 10, 20 and 40 min to the agents at 20 degrees C. An inactivation factor (IF) of > or = 5 log10 was used as the criterion for effective disinfection. This IF was achieved with every microorganism/disinfectant combination after 5 min exposure except in experiments with phage f2 and the 1% glutaraldehyde-based disinfectant. The diminished inactivation noticed with the 1% glutaraldehyde-based disinfectant supports the recommendation to use a disinfectant containing a minimum of 2% glutaraldehyde for high level disinfection.
Altered alertness of vasopressin-secreting transgenic mice.
We evaluated behavior and cognitive performance in a line of transgenic mice that overexpress the rat gene for vasopressin. Open field testing revealed greatest habituation in homozygous mice. Passive avoidance performance indicated equal learning and memory ability of transgenic compared to normal mice. Drinking behavior following exposure to 10% sucrose solution suggested diminished neophobia in homozygous mice. These observations are consistent with enhanced attention and alertness in the transgenic animals and support prior observations on the effects of vasopressin on behavior and cognitive function.
Sensitive detection of biotoxoids and bacterial spores using an immunomagnetic electrochemiluminescence sensor.
Extremely sensitive detection of various biotoxoids and bacterial spores using the commercial ORIGEN analyzer was achieved by capture on antibody-conjugated micron sized magnetic beads (MBs) followed by binding of ruthenium (II) trisbipyridal chelate (Ru(bpy)2+3-labelled reporter antibodies. Immunomagnetically captured target materials were collected on a magnet. Electrochemiluminescence (ECL) was evoked from the Ru(bpy)3(2+)-tagged reporter antibodies by application of an electrical potential. Femtogram sensitivity levels were obtained for all biotoxoids tested including botulinus A, cholera beta subunit, ricin and staphylococcal enterotoxoid B by this immunomagnetic (IM)-ECL approach. An IM-ECL assay for Bacillus anthracis spores yielded a detection limit of at least 100 spores. The ECL signal was a function of analyte quantity over several orders of magnitude, but the immunological 'hook' effect at high antigen loads made quantitation impossible over a broader range. All assays were performed with a maximum combined incubation and assay time of approximately 40 min. This work demonstrates the extreme sensitivity of the IM-ECL approach for soluble and particulate antigens.
Tuberculosis in the autopsy material: analysis of 1500 autopsies performed between 1972 and 1991 in the Institute of Tuberculosis and Chest Diseases, Warsaw, Poland.
SETTING: The present study is based on 1500 autopsies done in the Institute of Tuberculosis and Chest Diseases Warsaw, Poland during the years 1972-81 and 1982-91. OBJECTIVE: To assess the correctness of tuberculosis diagnosis before death in the above mentioned time periods. DESIGN: The autopsy reports were examined for the diagnosis of active tuberculosis proved by microscopy. The form and localisation of tuberculosis was assessed. The postmortem diagnosis was compared with clinical diagnosis. In those cases in which tuberculosis was not recognised before death the possible causes of this failure were analyzed. RESULTS: Active tuberculosis was found in 119 cases, 7.9% of all autopsies. It was localised in the lungs exclusively in 72 cases, in lungs and in extrapulmonary sites in 45 and in extrapulmonary sites only in 2. The frequency of active tuberculosis was the same for the two periods under evaluation. Tuberculosis was however not recognised before death in a much higher proportion of cases in 1982-92 (54%) than in 1972-81 (24%). The main cause of diagnostic failure was connected with atypical localisation of lesions on chest X-ray and with dissemination outside the lungs. Previous tuberculosis was a factor which facilitated the diagnosis of tuberculosis. CONCLUSIONS: In parallel with the decline of tuberculosis incidence in Poland, many doctors lack experience in diagnosing this disease, especially in cases with atypical X-ray presentation and with extrapulmonary localisation. This may lead to late or even very late diagnosis and have a significant impact on the epidemiological situation.