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Biomedical subjects

D Miller

Publications and source records attributed to D Miller.

At least 253 records · Page 14Linked to original sources

The economic costs of caring for people with HIV infection and AIDS in England and Wales.

The objectives of this study were firstly to estimate total lifetime care costs for an individual with HIV/AIDS, and secondly to estimate the total costs of caring people with HIV infection and AIDS in England and Wales between 1992 and 1997 inclusive. Questionnaires and monthly diaries were used to collate data on healthcare utilisation from patients with HIV infection over a 6-month period. These data were then used to estimate the annual total direct costs of care (stratified by disease stage), total lifetime costs of care, and present and future total national care costs for England and Wales. Costing data were obtained from providers of services throughout Greater London. In total, 235 patients with HIV infection were recruited from 2 clinics in Greater London. All costs were calculated in 1992-93 pounds sterling (pound; 1 pound = $US1.58, December 1995). Annual care costs were estimated at 4515 pounds ($US7134) for a person with asymptomatic HIV disease, 8836 pounds ($US13,961) for a person with symptomatic non-AIDS and 15 268 pounds ($US24,123) for a person with AIDS. Lifetime care costs were estimated at 84,522 pounds ($US133,545) per patient. The total costs of care for England and Wales were forecast to increase from 116,627,400 pounds ($US184,271,300) in 1992 to 162,638,100 pounds ($US256,968,200) in 1997. In conclusion, our study further emphasises the continued shift in hospital services from the inpatient sector to the outpatient sector. The importance of community care and informal care, in terms of the associated direct economic costs, is also highlighted. This emphasises the need for close collaboration between different agencies and strategic coordination of services. Finally, the study forecasts an increase in care costs in England and Wales during the 1990s.

Acquired Immunodeficiency Syndrome↗

Pyrrolosporin A, a new antitumor antibiotic from Micromonospora sp. C39217-R109-7. I. Taxonomy of producing organism, fermentation and biological activity.

Strain C39217-R109-7 (ATCC 53791) is an actinomycete strain isolated from a soil sample collected at Puerto Viejo, Peru. It produces a new antitumor antibiotic, designated pyrrolosporin A. Taxonomic studies on its morphological, cultural and physiological characteristics identified this producing strain as Micromonospora sp. C39217-R109-7. Pyrrolosporin A shows antimicrobial activity against Gram-positive bacteria and it is weakly active against Gram-negative bacteria. Pyrrolosporin A prolongs the life span of mice inoculated with P388 leukemia cells.

Animals↗

Improvements in health-related quality of life with sumatriptan treatment for migraine.

BACKGROUND: The debilitating effects of migraine might be reduced in patients using an effective migraine medication. The serotonin (5HT1) receptor agonist sumatriptan has been shown in clinical trials to alleviate headache and associated symptoms in the majority of patients treated. METHODS: Three hundred forty-four (344) patients with migraine were allowed to treat an unlimited number of migraine attacks for up to 24 months with subcutaneous sumatriptan (6 mg). Open-label oral sumatriptan (100 mg) could be used between 1 hour and 24 hours after the initial injection for treatment of recurrent or persistent headache. On four occasions during the treatment period, patients completed the Medical Outcomes Study Short Form-36 Health Survey, a general health status instrument; the Migraine-Specific Quality of Life Questionnaire, a disease-specific instrument; and a series of questions designed to measure the impact of migraine on productivity and disability. RESULTS: Treatment with sumatriptan was associated with significant (P < .05) improvements relative to baseline in three of the Short Form-36 Health Survey quality-of-life dimensions (Bodily Pain, General Health Perceptions, and Social Functioning) and three of the Migraine-Specific Quality of Life Questionnaire dimensions (Role Function-Restrictive, Role Function-Preventive, and Emotional Function). Significant (P < .05) improvements in patient-rated productivity and reductions in patient-rated disability also occurred during the trial. CONCLUSIONS: Patients using sumatriptan to treat migraines for up to 24 months experienced improvements in disability and productivity as well as in health-related quality of life as measured either by a general health status instrument or a disease-specific instrument.

Acute Disease↗

The Medication Reduction Project: combating polypharmacy in South Dakota elders through community-based interventions.

The Medication Reduction Project (MED RED) is a community-based program addressing polypharmacy issues in elders. Using educational presentations and one-on-one medication reviews conducted by a pharmacist specializing in geriatrics, MED RED reached over 1,100 older adults in rural and urban southeastern South Dakota communities during 1993. Analysis of the longitudinal data indicate that older adults participating in one-on-one reviews were on fewer medications, had dosage reductions, were more likely to take their medications as directed, and increased their use of non-pharmacological alternatives. These elders also reported feeling better, spent less money per month on medications, and offered indications of improved functioning and increased levels of independence. These findings suggest that education about medication use is a dynamic tool in empowering community-based older adults to be assertive participants in their own health care.

Aged↗

Damnacanthal is a highly potent, selective inhibitor of p56lck tyrosine kinase activity.

Damnacanthal, an anthraquinone isolated from a plant extract, was found to be a potent, selective inhibitor of p56lck tyrosine kinase activity. The structure, potency, and selectivity of damnacanthal were confirmed by independent synthesis and testing. Damnacanthal exhibited an IC50 of 17 nM for inhibition of p56lck autophosphorylation and an IC50 of 620 nM for phosphorylation of an exogenous peptide by p56lck. Damnacanthal had > 100-fold selectivity for p56lck over the serine/threonine kinases, protein kinase A and protein kinase C, and > 40-fold selectivity for p56lck over four receptor tyrosine kinases. It also demonstrated modest (7-20-fold), but highly statistically significant, selectivity for p56lck over the homologous enzymes p60src and p59fyn. Mechanistic studies demonstrated that damnacanthal was competitive with the peptide binding site, but mixed noncompetitive with the ATP site. Although damnacanthal contains a potentially reactive aldehyde moiety, equilibrium dialysis experiments demonstrated that significant amine formation between damnacanthal and amines occurred only at high concentrations of reactants. However, damnacanthal appeared to bind nonspecifically to membrane lipids and was not active in whole cell tyrosine kinase assays. Damnacanthal is the most potent, selective inhibitor of p56lck tyrosine kinase activity described to date and may represent the starting point for the identification of novel, selective inhibitors of p56lck which are active in whole cell as well as in cell-free systems.

Alkaloids↗

HCl absorption toward Sagittarius B2.

We have detected the 626 GHz J = 1 --> 0 transition of hydrogen chloride (H35Cl) in absorption against the dust continuum emission of the molecular cloud Sagittarius B2. The observed line shape is consistent with the blending of the three hyperfine components of this transition by the velocity profile of Sgr B2 observed in other species. The apparent optical depth of the line is tau approximately 1, and the minimum HCl column density is 1.6 x 10(14) cm-2. A detailed radiative transfer model was constructed which includes collisional and radiative excitation, absorption and emission by dust, and the radial variation of temperature and density. Good agreement between the model and the data is obtained for HCl/H2 approximately 1.1 x 10(-9). Comparison of this result to chemical models indicates that the depletion factor of gas-phase chlorine is between 50-180 in the molecular envelope surrounding the SgrB2(N) and (M) dust cores.

Astronomical Phenomena↗

Trends in mortality from melanoma in Canada and prediction of future rates.

A long term increase in incidence of and mortality due to malignant melanoma has been observed in all well documented white populations. The major identified cause of melanoma is sun exposure. One would expect predictions of future atmospheric ozone depletion to lead to an increase in ultraviolet radiation (UVR) and in the effects of sun exposure. We consider age-period data for Canadian malignant malanoma mortality. We fit a multiplicative exponential/logistic (MEL) model to the data and extrapolate to AD 2010 hence yielding point estimates of future rates. We obtain total mortality forecasts by multiplying rates by population estimates. We present standard errors for forecasts. We forecast that melanoma will be a much larger burden on the health care system in the early years of the next century than it is at present. We obtain an age-cohort model by a simple transformation of the age-period model. Also, we obtain unconditional probabilities of death due to melanoma both for age-period and age-cohort models. We discuss the assumptions underlying the MEL model that suggest possible relationships between UVR and melanoma.

Adult↗

Folate receptor type gamma is primarily a secretory protein due to lack of an efficient signal for glycosylphosphatidylinositol modification: protein characterization and cell type specificity.

A novel isoform of the human folate receptor (FR, type gamma) was recently identified in hematopoietic tissues [Shen et al. (1994) Biochemistry 33, 1209-1215]. In that report, Cos-1 cells, transiently transfected with the cDNA for FR-gamma, produced relatively poor expression of the receptor on the cell surface. In this study, several recombinant Chinese hamster ovary (CHO) cell lines were produced by stable transfection with the cDNA for FR-gamma followed by amplification. Similar recombinant CHO cell lines were produced that expressed the glycosylphosphatidylinositol-(GPI-) anchored FR type beta and a truncated form of FR type beta (FR-beta delta), in which the normal carboxyl-terminal signal for GPI anchor attachment was deleted. Both FR-gamma-and FR-beta delta-expressing CHO cells produced a [3H]folic acid binding protein in the medium with a similar time course over a 24-h period; in contrast to intact FR-beta, relatively insignificant amounts of either FR-gamma or FR-beta delta were associated with the CHO cell surface and this was unaltered by the absence of serum in the medium. The FR-gamma- and FR-beta delta-producing CHO cells did not differ significantly in intracellular FR levels. Furthermore, the mRNA level for FR-gamma did not exceed that for FR-beta delta. When deglycosylated with hydrogen fluoride, both FR-gamma and FR-beta delta showed similar apparent molecular weights on Western blots as predicted for the intact polypeptides.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Current spectrum of cardiogenic shock and effect of early revascularization on mortality. Results of an International Registry. SHOCK Registry Investigators.

BACKGROUND: Cardiogenic shock remains the leading cause of death of patients hospitalized with acute myocardial infarction (MI). This study was conducted to examine (1) the current spectrum of cardiogenic shock, (2) the proportion of patients who are potential candidates for a trial of early revascularization, and (3) the apparent impact of early revascularization on mortality. METHODS AND RESULTS: Nineteen participating centers in the United States and Belgium prospectively registered all patients diagnosed with cardiogenic shock. Two hundred fifty-one patients were registered. The mean age was 67.5 +/- 11.7 years, and 43% were women. Acute mitral regurgitation or ventricular septal rupture was the cause of shock in 8%. Concurrent conditions contributing to the development of shock were noted in 5%, and 2% had isolated right ventricular shock. Among the remaining 214 patients, nonspecific findings on the ECG associated with "nontransmural" MI were seen in 14%. The median time to shock diagnosis after MI was 8 hours. The overall in-hospital mortality was 66%. Patients clinically selected to undergo cardiac catheterization were significantly younger and had a lower mortality than those not selected (51% versus 85%, P < .0001) even if they were not revascularized (58%). Mortality for patients undergoing percutaneous transluminal coronary angioplasty (PTCA) was 60% (n = 55) and 19% (n = 16) for coronary artery bypass graft surgery (CABG). Sixty percent (n = 150) of registered patients were judged eligible for a trial of early revascularization. Trial-eligible patients were significantly younger (65.4 +/- 11.0 versus 70.6 +/- 11.9 years, P < .001), had an earlier median time to shock onset after MI (6.5 versus 17.5 hours, P = .003), and had lower mortality (62% versus 73%, P = .077) than ineligible patients. CONCLUSIONS: Patients diagnosed with cardiogenic shock complicating acute MI are a heterogeneous group. Those eligible for a trial of early revascularization tended to have lower mortality. Patients selected to undergo cardiac catheterization had lower mortality whether or not they were revascularized. Emergent PTCA and CABG are promising treatment modalities for cardiogenic shock, but biased case selection for treatment may confound the data. Whether PTCA and CABG reduce mortality and which patient subgroups benefit most remain to be determined in a randomized clinical trial.

Aged↗

Chemoradiotherapy for organ preservation in oral and pharyngeal carcinoma.

OBJECTIVES: To use concurrent chemoradiotherapy as primary treatment for resectable head and neck squamous cell carcinoma to (1) demonstrate the feasibility of an organ preservation approach for nonlaryngeal sites; (2) evaluate the toxic reactions and response to a new combination of two platinum compounds; and (3) monitor the effect of therapy on oral and pharyngeal function. DESIGN: Case series, a prospective single-armed trial. SETTING: Tertiary referral center. PATIENTS: Twenty-two patients with head and neck squamous cell carcinoma of the oral cavity, oropharynx, and hypopharynx for whom surgery would significantly compromise function were entered in this trial. INTERVENTION: Standard fractionation external-beam radiation therapy (2 Gy/Fx; total, 70 Gy) was given during a 9-week period, including a 2-week break after 40 Gy, concurrently with eight weekly doses of carboplatin and three doses of cisplatin (100 mg/m2) at 3-week intervals. A biopsy was performed 12 weeks after the completion of chemoradiotherapy to assess clinical response. All patients presenting with nodes greater than 3 cm had planned neck dissection. MAIN OUTCOME MEASURES: Tumor response, toxic reactions, survival, and oral and pharyngeal function. RESULTS: Overall complete response was 86%. Estimated overall 2-year survival was 64%, and disease-specific survival was 71% (median follow-up time, 25 months). Five patients have died of disease and two of unrelated causes. Treatment was completed by all, with toxic reactions including myelosuppression, mucositis, and dysphagia. Half of the patients required gastrostomy. CONCLUSIONS: Concurrent chemoradiotherapy using two platinum analogues was tolerated with good local control and survival. Notable dysphagia was common. This study provides pilot data for randomized clinical trials to confirm the usefulness of chemoradiotherapy for nonlaryngeal organ preservation.

Adult↗

Symptoms of schizophrenia. Methods, meanings, and mechanisms.

BACKGROUND: The "group of schizophrenias," normally referred to with a single nominative, is phenomenologically heterogeneous. Its symptoms represent multiple psychological domains, including perception, inferential thinking, language, attention, social interaction, emotion expression, and volition. Studies of psychopathology have simplified this complex array in several ways, one of which is a subdivision into positive and negative symptoms. METHODS: This study examined the positive vs negative distinction in a sample of 243 patients with schizophrenia or schizophreniform disorder who were evaluated with the Scale for the Assessment of Negative Symptoms and the Scale for the Assessment of Positive Symptoms. A two-stage factor analysis was applied, beginning with a principal components analysis applying varimax rotation, followed by an extension analysis. The purpose of these analyses was to evaluate the correlational relationships of the various symptoms of schizophrenia. RESULTS: The results confirmed previous reports by our group and others suggesting that the symptoms of schizophrenia fall into three natural dimensions, as assessed by the correlational interrelationships: positive symptoms subdivide into psychotic and disorganized dimensions, while a third negative dimension also emerges. CONCLUSION: Because these dimensions have impressive consistency across studies, future work must examine their relationship to clinically relevant concepts such as prognosis or etiology and examine four different aspects: longitudinal course, neural mechanisms, relationship to treatment, and interrelationships in other pathological conditions.

Age of Onset↗

A longitudinal study of symptom dimensions in schizophrenia. Prediction and patterns of change.

BACKGROUND: Factor analytic studies have suggested that the symptoms of schizophrenia may be divided into three uncorrelated dimensions. This study examines the longitudinal course of the symptoms of schizophrenia using this three-dimensional perspective. METHODS: The sample was composed primarily of neuroleptic-naive patients suffering from schizophrenia. Subjects were studied in a prospective longitudinal design, with comprehensive structured assessments at index, discharge, and 6-month intervals after discharge over a 2-year period. RESULTS: Negative symptoms were already relatively prominent at the time of index evaluation; they tended to remain stable throughout the follow-up period. The two dimensions of positive symptoms, psychoticism and disorganization, although prominent at index evaluation, declined over the course of the follow-up period and tended to be less stable. A longitudinal factor analysis was conducted to determine whether the changes in symptoms followed any consistent pattern. We observed that all three groups of symptoms tended to change in unison and independently from one another. CONCLUSIONS: These results suggest that these three dimensions of psychopathology show different patterns of exacerbation and remission during the course of schizophrenia. This independent pattern of evolution suggests that these three dimensions should be studied further with respect to response to treatment, cognitive mechanisms, psychosocial correlates, and neural substrates.

Adult↗