Search PubMedSearch

Biomedical subjects

D Miller

Publications and source records attributed to D Miller.

At least 37 records · Page 2Linked to original sources

Rescue of Drosophila labial null mutant by the chicken ortholog Hoxb-1 demonstrates that the function of Hox genes is phylogenetically conserved.

Hox complexes are important players in the establishment of the body plan of invertebrates and vertebrates. Sequence comparison demonstrates a remarkable phylogenetic conservation of key structural features of Hox genes. The correlation between the physical order of genes along the chromosomes and their domains of function along the body axis is conserved between arthropods and vertebrates. Ectopic expression experiments suggest that the functions of homeo proteins also are conserved between invertebrates and vertebrates. However, it remains an open question whether vertebrate Hox genes expressed under the control of Drosophila regulatory sequences can substitute the function of Drosophila Hox genes. We have studied this issue with the Drosophila labial (lab) gene and its chicken ortholog gHoxb-1. We fused the entire protein-coding region of gHoxb-1 with previously identified regulatory sequences of lab. This approach places gHoxb-1 into the normal embryonic spatiotemporal context in which lab acts. Ten transgenic lines carrying gHoxb-1 were established and tested for their ability to rescue lab null mutant animals. Eight lines rescued with high efficiency, embryonic lethality, and abnormal head morphogenesis, two defects observed in lab null mutant embryos. The rescue with the gHoxb-1 minigene was close to the efficiency of that obtained with the Drosophila lab minigene. This indicates that gHoxb-1 protein can regulate lab target genes and thereby restore embryonic viability. This is striking, as Lab and gHoxb-1 proteins are divergent except for their homeo domains and a short stretch of amino acids amino-terminal to the homeo domain. Our findings demonstrate a functional conservation of the lab class homeo proteins between insects and vertebrates and support the view that function of Hox genes resides in relatively few conserved motifs and largely in the homeo domain.

Amino Acid Sequence

Association of elevated serum lipid levels with retinal hard exudate in diabetic retinopathy. Early Treatment Diabetic Retinopathy Study (ETDRS) Report 22.

OBJECTIVE: To evaluate the relationship between serum lipid levels, retinal hard exudate, and visual acuity in patients with diabetic retinopathy. DESIGN: Observational data from the Early Treatment Diabetic Retinopathy Study. PARTICIPANTS: Of the 3711 patients enrolled in the Early Treatment Diabetic Retinopathy Study, the first 2709 enrolled had serum lipid levels measured. MAIN OUTCOME MEASURES: Baseline fasting serum lipid levels, best-corrected visual acuity, and assessment of retinal thickening and hard exudate from stereoscopic macular photographs. RESULTS: Patients with elevated total serum cholesterol levels or serum low-density lipoprotein cholesterol levels at baseline were twice as likely to have retinal hard exudates as patients with normal levels. These patients were also at higher risk of developing hard exudate during the course of the study. The risk of losing visual acuity was associated with the extent of hard exudate even after adjusting for the extent of macular edema. CONCLUSIONS: These data demonstrate that elevated serum lipid levels are associated with an increased risk of retinal hard exudate in persons with diabetic retinopathy. Although retinal hard exudate usually accompanies diabetic macular edema, increasing amounts of exudate appear to be independently associated with an increased risk of visual impairment. Lowering elevated serum lipid levels has been shown to decrease the risk of cardiovascular morbidity. The observational data from the Early Treatment Diabetic Retinopathy Study suggest that lipid lowering may also decrease the risk of hard exudate formation and associated vision loss in patients with diabetic retinopathy. Preservation of vision may be an additional motivating factor for lowering serum lipid levels in persons with diabetic retinopathy and elevated serum lipid levels.

Adult

Integrated backscatter for quantification of left atrial spontaneous echo contrast.

OBJECTIVES: This study was designed to develop a quantitative method of spontaneous echo contrast (SEC) assessment using integrated backscatter and to compare integrated backscatter SEC measurement with independent qualitative grades of SEC and clinical and echocardiographic predictors of thromboembolism. BACKGROUND: Left atrial SEC refers to dynamic swirling smokelike echoes that are associated with low flow states and embolic events and have been graded qualitatively as mild or severe. METHODS: We performed transesophageal echocardiography in 43 patients and acquired digital integrated backscatter image sequences of the interatrial septum to internally calibrate the left ventricular cavity and left atrial cavity under different gain settings. Patients were independently assessed as having no, mild or severe SEC. We compared intensity of integrated backscatter in the left atrial cavity relative to that in the left ventricular as well as to the independently assessed qualitative grades of SEC. Fourier analysis characterized the temporal variability of SEC. The integrated backscatter was compared with clinical and echocardiographic predictors of thromboembolism. RESULTS: The left atrial cavity integrated backscatter intensity of the mild SEC subgroup was 4.7 dB higher than that from the left ventricular cavity, and the left atrial intensity of the severe SEC subgroup was 12.5 dB higher than that from the left ventricular cavity. The left atrial cavity integrated backscatter intensity correlated well with the qualitative grade. Fourier transforms of SEC integrated backscatter sequences revealed a characteristic dominant low frequency/high amplitude spectrum, distinctive from no SEC. There was a close relationship between integrated backscatter values and atrial fibrillation, left atrial size, left atrial appendage flow velocities and thrombus. CONCLUSIONS: Integrated backscatter provides an objective quantitative measure of SEC that correlates well with qualitative grade and is closely associated with clinical and echocardiographic predictors of thromboembolism. The relationship between integrated backscatter measures and cardioembolic risk will be defined in future multicenter studies.

Aged

Follow-up study of adolescent girls with a history of premature pubarche.

A total of 37 girls with a history of benign premature pubarche were followed into puberty; a disproportionate number of girls experienced early menarche. Twenty-five had some degree of acne, 14 had hirsutism, and 5 had acanthosis nigricans. Body mass index (BMI) at initial presentation correlated with postpubertal BMI and was weakly correlated with postpubertal hirsutism.

Acanthosis Nigricans

Laparoscopic lateral ovarian transposition.

OBJECTIVE: To determine if the new technique laparoscopic lateral transposition of the ovaries before pelvic radiotherapy for anal canal carcinoma prevents radiation-related ovarian failure. DESIGN: A case report. SETTING: The operating room of a Canadian teaching hospital. PATIENTS: A single patient with anal canal carcinoma, requiring pelvic radiotherapy, who desired preservation of ovarian function. INTERVENTIONS: Laparoscopic ovarian transposition to the level of the pelvic brim. MAIN OUTCOME MEASURES: Follow-up clinical and laboratory evidence of ovarian failure. RESULTS: Initially ovarian failure was confirmed with the appearance of postmenopausal symptoms and the elevation of serum gonadotropins. These symptoms resolved by 8 months after radiotherapy, normal menstrual cycles resumed, and normal FSH levels were detected at that time. CONCLUSIONS: The laparoscopic, lateral transposition of this patient's ovaries was effective at preventing radiation-related ovarian failure.

Adult

Endophthalmitis associated with microbial keratitis.

PURPOSE: The purpose of the study is to investigate possible risk factors, organisms cultured, and visual acuity outcomes of endophthalmitis associated with microbial keratitis. METHODS: Records were reviewed of all patients with both positive corneal and positive intraocular cultures at the Bascom Palmer Eye Institute between January 1, 1990, and March 31, 1995. RESULTS: Thirteen (92.9%) of 14 patients identified had documented keratitis before the diagnosis of endophthalmitis was made. Thirteen (92.9%) patients recently had used 1% prednisolone acetate eye drops, 2 (14.3%) received oral prednisone, and 5 (35.7%) were being treated for systemic conditions associated with relative immune dysfunction. Eight (57.1%) patients had a history of ocular surgery, and seven (50.0%) had wound abnormalities. Eight (57.1%) patients lacked an intact posterior capsule, four (28.6%) had a corneal perforation, and three (21.4%) had a history of dry eye. Gram-negative organisms (7), Staphylococcus aureus (3), streptococcal species (2), and fungi (4) were the most frequently isolated organisms. Coagulase-negative staphylococci were not isolated. Six (42.9%) patients achieved a post-treatment visual acuity of 20/200 or better. Three (21.4%) patients underwent enucleation or evisceration. Although not statistically significant, there was an association between appropriate initial antibiotic therapy and improved visual outcomes. CONCLUSION: Patients in whom endophthalmitis associated with microbial keratitis develops have a frequent history of corticosteroid use, systemic conditions associated with relative immune dysfunction, lack of an intact posterior capsule, dry eye, wound abnormalities, and/or corneal perforation. In general, agents cultured consisted of organisms less frequently reported to be the causative agents in series of postoperative and post-traumatic endophthalmitis. Post-treatment visual outcomes generally were poor.

Anti-Inflammatory Agents

Proton dosimetry intercomparison.

BACKGROUND AND PURPOSE: Methods for determining absorbed dose in clinical proton beams are based on dosimetry protocols provided by the AAPM and the ECHED. Both groups recommend the use of air-filled ionization chambers calibrated in terms of exposure or air kerma in a 60Co beam when a calorimeter or Faraday cup dosimeter is not available. The set of input data used in the AAPM and the ECHED protocols, especially proton stopping powers and w-value is different. In order to verify inter-institutional uniformity of proton beam calibration, the AAPM and the ECHED recommend periodic dosimetry intercomparisons. In this paper we report the results of an international proton dosimetry intercomparison which was held at Loma Linda University Medical Center. The goal of the intercomparison was two-fold: first, to estimate the consistency of absorbed dose delivered to patients among the participating facilities, and second, to evaluate the differences in absorbed dose determination due to differences in 60Co-based ionization chamber calibration protocols. MATERIALS AND METHODS: Thirteen institutions participated in an international proton dosimetry intercomparison. The measurements were performed in a 15-cm square field at a depth of 10 cm in both an unmodulated beam (nominal accelerator energy of 250 MeV) and a 6-cm modulated beam (nominal accelerator energy of 155 MeV), and also in a circular field of diameter 2.6 cm at a depth of 1.14 cm in a beam with 2.4 cm modulation (nominal accelerator energy of 100 MeV). RESULTS: The results of the intercomparison have shown that using ionization chambers with 60Co calibration factors traceable to standard laboratories, and institution-specific conversion factors and dose protocols, the absorbed dose specified to the patient would fall within 3% of the mean value. A single measurement using an ionization chamber with a proton chamber factor determined with a Faraday cup calibration differed from the mean by 8%. CONCLUSION: The adoption of a single ionization chamber dosimetry protocol and uniform conversion factors will establish agreement on proton absorbed dose to approximately 1.5%, consistent with that which has been observed in high-energy photon and electron dosimetry.

Calibration

Identification and mapping of a putative bombesin receptor gene on human chromosome 17q21.3+.

A mouse bombesin receptor cDNA was used as a probe to screen a human P1 genomic library. Clone HBR1 was isolated and used to localize a putative human bombesin receptor gene (HBRKS) on human chromosome 17q21.3 by fluorescent in situ hybridization (FISH). HBRKS was identified and mapped by polymerase chain reaction (PCR) amplification from a Yeast artificial chromosome (YAC) contig spanning 17q21-q23. In addition, a few candidate genes were found by exon-trapping from HBR1.

Animals

Impact of sumatriptan on workplace productivity, nonwork activities, and health-related quality of life among hospital employees with migraine.

This prospective, open-label study evaluated the effects of subcutaneous sumatriptan versus usual therapy on workplace productivity, activity time outside of work, and health-related quality of life in 43 men or women who were hospital employees diagnosed with migraine according to international Headache Society criteria. Patients treated migraines with their usual therapy for 12 to 18 weeks followed by subcutaneous sumatriptan for 6 months. Health-related quality of life measurements obtained at baseline, after usual therapy, and after sumatriptan therapy included the Short Form-36 Health Survey and the Migraine-Specific Quality of Life Questionnaire. Patient daily diaries were used to capture data on migraine symptoms and on Lost Workplace Productivity and Non-workplace Activity Time. Traditional clinical efficacy measures were obtained to support the pharmacoeconomic data. Clinical data showed that the percentage of treated migraine days per patient on which the patient experienced relief (moderate or severe pain reduced to mild or none) was 75% with sumatriptan and 25% with usual therapy. The mean time to meaningful relief was 1.1 hours during the sumatriptan phase and 4.2 hours during the usual therapy phase. Lost Workplace Productivity and Nonworkplace Activity Time was 35% lower with sumatriptan therapy (1.5 hours) compared with usual therapy (2.3 hours). Time missed from work due to symptoms, time worked with symptoms, and time normal activities were carried on with symptoms were each lower during sumatriptan therapy compared with usual therapy. Scores on each of the three Migraine-Specific Quality of Life Questionnaire dimensions and on the Role-Emotional dimension of the Short Form-36 were significantly more favorable after sumatriptan than after usual therapy (P < 0.05). These data demonstrate that treatment of migraines with sumatriptan for 6 months following usual therapy for 12 to 18 weeks was associated with improvement in clinical efficacy, reduction in lost workplace productivity and nonworkplace activity time, and enhancement of key dimensions of health-related quality of life among employees of a large university hospital.

Activities of Daily Living

Bartonella (Rochalimaea) quintana causing fever and bacteremia in an immunocompromised patient with non-Hodgkin's lymphoma.

A 48-yr-old man with stage IV non-Hodgkin's lymphoma, became neutropenic following chemotherapy and developed a fever. His blood cultures were processed to enhance the yield of fastidious bacteria. A slow-growing, capnophilic Gram-negative rod was isolated. The febrile episode was treated with cefotaxime, imipenem and vancomycin and resolved. The bacterial isolate was identified as Bartonella (Rochalimaea) quintana by 16S-rDNA gene sequencing. The isolate showed 99.8% sequence homology with the type strain. This is the first isolation of Bartonella (Rochalimaea) quintana from a bacteremic patient in Australia. This bacterium is a fastidious Gram-negative rod requiring prolonged culture for its isolation. Patients with culture-negative pyrexia, especially immunocompromised patients, may need to be investigated for infection with this agent.

Bacteremia

Community service needs of people with HIV infection in London.

The objectives of this study were to describe the expressed needs for community services of HIV-infected individuals by disease stage, gender and transmission category and the barriers which prevent the receipt of such services. Structured interviewer-administered questionnaires concerning a 6-month retrospective period were used to obtain information on need for community services and problems which prevented the receipt of services. The study sample included 70 homosexual men with asymptomatic HIV disease, 42 homosexual men with symptomatic non-AIDS, 53 homosexual men with AIDS, 23 heterosexual men, 29 heterosexual women, 9 male and 9 female injecting drug users. The main outcome measures were the extent to which needs for community services were met and person/service combinations for which problems or barriers prevented the receipt of community services. On average, subjects expressed a need for 10 categories of community services over the 6-month period: homosexuals expressed a mean of 10, heterosexuals 10, injecting drug users 11, subjects with asymptomatic HIV infection 9, subjects with symptomatic non-AIDS 11, subjects with AIDS 13, men 9 and women 14. A total of 58% of community service needs were always met, 6% were rarely not met, 16% were sometimes not met, 6% were often not met and 14% were not met at all. The extent to which subjects felt that their needs were met was similar for the different study groups, but the needs of women were met somewhat less frequently than those of men. Similarly, people with AIDS felt that their needs were met slightly less often. Reported levels of unmet need were high for a wide range of services. The most common reason subjects gave for not having received a community service for which they expressed a need was ignorance of where or how to obtain the service. This was mentioned in one-third of all such cases. Anxieties over the competence with which a service would be rendered was mentioned in 13% of cases and long waiting times in 11%. The frequencies of unmet need for many community services were high and often seemed to arise either from a lack of awareness on the part of subjects on how and where services could be obtained or from doubts about the relevance of services offered. Both of these barriers should be surmountable through the provision of better information to patients, extending user involvement in service development and the better co-ordination of service delivery through care management approaches.

Adult

Is there life after work? Experiences of HIV and oncology health staff.

A cross-sectional interview survey of 103 HIV/AIDS and 100 oncology staff in nine treatment sites in London aimed to identify ways in which work stress affected domestic and social lives of such staff. In all staff one-third of those without long-term emotional relationships stated they felt their work formed a barrier to their being involved in that way. Most subjects reported spending a considerable amount of time discussing work with partners, and work-related subjects caused conflict for just under half of the total sample. Thirty-nine percent reported their partners complained regularly about their commitment to work, and one-quarter overall reported their relationship had suffered as a result of their work in HIV or oncology. Using tests of association comparing group responses to structured interview and standardized psychometric items, few differences were found overall between staff in HIV/AIDS and staff in oncology. HIV staff were more likely to be motivated to work through peer concern, and friends of HIV staff were more likely to be supportive of their working in such a field. On the other hand, families of oncology staff were more supportive of their work than were families of HIV staff HIV staff were more likely to have had a family member who had suffered from a chronic or life-threatening disease. HIV staff were less likely to avoid discussing their work socially. Suggestions for addressing the potentially corrosive impact of health care in these fields, based on these samples, are made.

Adult

Sudden cardiac death due to primary coronary sinus thrombosis.

Coronary sinus thrombosis has been reported only as a complication of cardiac transplantation and right heart catheterization in noninfected patients. We report a case of acute coronary sinus thrombosis occurring in the absence of these procedures and resulting in sudden cardiac death.

Aged

A case report of paroxysmal dystonic choreoathetosis due to hypoglycaemia induced by an insulinoma.

Hypoglycaemia due to an insulinoma can mimic acute disorders of cognition, consciousness, epilepsy, transient ischaemia, or psychosis, and chronic disorders of dementia and neuropathy. Misdiagnosis and delay in treatment are common and prolonged hypoglycaemia can lead to permanent neurological deficit or fatal coma. A 27 year old woman with hypoglycaemia induced by an insulinoma presented with features typical of paroxysmal non-kinesiogenic dystonic choreoathetosis. Striatal dysfunction as a consequence of hypoglycaemia has rarely been described. Insulinoma is a readily treatable condition that should be considered in the differential diagnosis of a paroxysmal movement disorder.

Adult

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