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Biomedical subjects

W Hill

Publications and source records attributed to W Hill.

At least 19 recordsLinked to original sources
PubMed1999

A three-dimensional model of the mouse at embryonic day 9.

This paper describes a digital, three-dimensional model of the mouse embryo at E9. The model was made by reconstruction from images of serial histological sections digitally warped to remove distortions and has a resolution of approximately 9 microns. The model can be digitally resectioned in any plane to provide images which resemble conventional histological sections. The main tissues have been identified and delineated by digital painting so that the anatomical components can be visualized and manipulated in 3-D surface- and volume-rendered views. This provides a three-dimensional definition of anatomy that will provide a useful tool for interpreting and understanding spatial data in mouse embryos. The anatomy of the model is discussed where it provides landmarks for interpretation and navigation or where it is unexpected in light of existing descriptions of the E9 mouse embryo. The complete anatomy is not presented in this paper but will be available on CD-ROM. A detailed description of the technical aspects of the construction of the model is included in an appendix. The model is the first of a series that will form the basis for an atlas/database of mouse development. This reconstruction and its associated anatomy are available in a variety of data formats with some supporting software from http:@genex.hgu.mrc.ac.uk/.

Anatomy, Cross-Sectional↗
PubMed1999

Long-term outcome of hairy cell leukemia treated with 2-chlorodeoxyadenosine.

The long-term results of both pretreated and previously untreated patients with hairy cell leukemia (HCL) using uniformly a single 7-day course of 2-chlorodeoxyadenosine (2-CdA) by continuous infusion are reported. In addition, the probability of obtaining another response with this drug in patients who relapsed after 2-CdA treatment will be addressed. Forty-two consecutive patients (32 men, 10 women) with a median age of 56 years (range 32-75) at the time of initiation of 2-CdA treatment were analyzed. Ten patients were pretreated with either splenectomy (n=6) or interferon a (n=8) or deoxycoformycin (dCF) (n=3) or with all procedures in sequence. Two patients who did not respond to dCF did respond to 2-CdA. Median time to start of 2-CdA treatment of the ten pretreated patients was 47 months (10-160); 41 of the 42 (98%) achieved CR, and one patient reached a good partial response with a single cycle of 2-CdA. Ten of the 42 patients had no toxicities at all. Toxicities (WHO grades I-IV) were mainly of grades I and II; in one patient with a preexisting brain injury grade III neurotoxicity was seen, and one patient suffered a grade-IV infectious complication. Bone marrow biopsies were performed at the time of recovery of hematopoiesis, thereafter at 2- to 3-month intervals, then at 6 months, and finally annually in all 42 patients. Median follow-up is 32 months (2-72). Disease-free survival from start of 2-CdA treatment is 75% at 6 years; 6/42 patients relapsed. Three of these patients were treated with 2-CdA again. All three patients reached another CR (+1, +2, +13). Four of the 42 patients had a second malignancy (carcinomas of the bladder, breast, cervix, prostate gland) before receiving 2-CdA. One patient died in CR due to the second malignancy. 2-CdA is a safe and effective treatment of HCL, inducing complete remissions in the majority of patients with only a single cycle of 2-CdA and a paucity of toxicities. Responses are durable and long lasting. Patients relapsing following a treatment with 2-CdA seem to respond to this drug again.

Adult↗
PubMed1999

Reliable operant apparatus for fish: audio stimulus generator, response button, and pellet-dispensing nipple.

As part of ongoing research into the ability of koi to categorize complex auditory stimuli, we have had to develop novel apparatus. The stimulus generator presents sound from two CD drives under computer control through a new underwater speaker. The operant manipulandum is a horizontal button that eliminates spurious triggering by water turbulence and problematic response topographies. The button's design has also been adapted for use by tilapia in an aquacultural food-preference study. The feeder uses a nipple to dispense food pellets reliably under water. In this paper, the apparatus is described in detail. Also discussed are methodological issues related to its design, as well as its usage in a pilot study in which koi learned to discriminate music from silence by using a single manipulandum with food reinforcement.

Animals↗
PubMed1998

Diabetes complications and risk factors in an Australian population. How well are they managed?

BACKGROUND: This study aimed to explore the relationship between complications and risk factors in the type 2 diabetes population, and to assess the level of assistance people with diabetes receive in controlling their risk factors. METHODS: Participants were recruited from representative population surveys of South Australians aged over 18 years. Participants were asked a series of questions about their risk factors and the advice and assistance they received from their general practitioner (GP) in modifying their risk factors. Additionally, participants were clinically tested for a number of macro and microvascular complications. RESULTS: South Australians with type 2 diabetes have a high prevalence of risk factors, with the majority being overweight or obese, doing no vigorous exercise and having high blood pressure. They also have a high prevalence of complications, with 53% having at least one macrovascular complication and 66% having at least one microvascular complication. Additionally, participants reported high levels of GP advice and assistance on the risk factors where pharmacological controls were available, but low levels of assistance where non-pharmacological interventions were needed to control the risk factor. CONCLUSIONS: The prevalence of diabetes risk factors and complications among South Australians with type 2 diabetes is a cause for concern, as is the lack of assistance offered by GPs to modify risk factors. Multi-disciplinary approaches to the control of risk factors and patient self-management and education are critical to the progression and success of diabetes care.

Adult↗
PubMed1998

Phase II study of dexverapamil plus anthracycline in patients with metastatic breast cancer who have progressed on the same anthracycline regimen.

The purpose of this study is to evaluate whether metastatic breast cancer that has progressed on an anthracycline-containing drug regimen will subsequently respond to that identical regimen if dexverapamil, a modulator of P-glycoprotein-mediated drug resistance, is given concomitantly. Eligible patients received 180 mg/m2 dexverapamil every 6 h for 15 doses with the anthracycline administered 30 min after the seventh dose. Blood for dexverapamil levels was drawn before and 30 min after this dose. When possible, biopsies were obtained to measure mdr-1 expression by reverse transcription-PCR and by image cytometry. Of the 21 patients entered onto the trial, 20 were evaluable for response. There were two partial responses (10%) that both lasted for 6 months, and two additional patients had stable disease. Seven patients had asymptomatic cardiotoxicity consisting of hypotension (24%), bradycardia (5%), or prolongation of the P-R interval (14%). Two patients developed acute congestive heart failure, one on dexverapamil and one 10 days after stopping it. Dexverapamil did not seem to increase anthracycline toxicity. The median trough dexverapamil plus norverapamil level on day 3 was 1110 ng/ml (range, 186-3385 ng/ml), and the median peak level was 2164 ng/ml (range, 964-8382 ng/ml). There was poor correlation between reverse transcription-PCR and image cytometry for the level of mdr-1 expression. Because dexverapamil has been shown to affect doxorubicin pharmacokinetics subsequent to the initiation of this trial, it cannot be concluded that the responses seen were necessarily due to P-glycoprotein inhibition. Additional studies are necessary to determine whether mdr-1 modulators can reverse clinical drug resistance in breast cancer patients. The intrinsic cardiotoxicity of dexverapamil makes it less suitable for such studies than several other available agents.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

A randomized trial of paracentesis plus intraperitoneal tumor necrosis factor-alpha versus paracentesis alone in patients with symptomatic ascites from recurrent ovarian carcinoma.

PURPOSE: Previous phase I and II studies of intraperitoneal recombinant human tumor necrosis factor-alpha (rhTNF-alpha) suggested a high degree of efficacy in reducing or eliminating ascitic fluid. To more accurately determine the efficacy of this agent, the role of paracentesis versus paracentesis plus intraperitoneal rhTNF-alpha was studied in a randomized trial. PATIENTS AND METHODS: Thirty-nine patients with symptomatic ascites with a volume of > 1000 ml from recurrent epithelial ovarian carcinoma or primary peritoneal carcinoma, which was refractory to standard therapy, were randomized either to receive 0.06 mg/m2 rhTNF-alpha (Knoll, Canada) (the dose determined optimal from phase I and II studies) intraperitoneally after drainage of fluid or to receive drainage alone. A maximum of three treatments were given at weekly intervals. Eighteen patients were randomized to receive rhTNF-alpha. RESULTS: None of 18 evaluable rhTNF-alpha patients had either a complete response (CR) (no clinical evidence of ascites and < 400 ml of fluid on ultrasound) or a partial response (PR) (asymptomatic ascites and < or = 1000 ml of fluid ultrasound). There were no CRs or PRs in the 17 evaluable patients who received drainage alone. The intraperitoneal infusion of rhTNF-alpha was generally well tolerated. Moderate to severe toxicity consisted of pain/discomfort in 42.1%, fever/chills in 36.9%, nausea/vomiting in 10.5%, edema in 10.5%, and hypotension in 5.3% of patients receiving rhTNF-alpha. CONCLUSION: rhTNF-alpha, as given in this study, was not effective in preventing recurrence of ascites in this patient population.

Ascites↗
PubMed1997

The mouse atlas and graphical gene-expression database

The large amounts of gene-expression data on mouse development are now too extensive to be stored in any format other than that of a database. Furthermore, as this data is intrinsically graphical and as, in the early developmental stages at least, its boundaries do not map directly to those of anatomical tissues, the natural way to store it is in graphical format. We are therefore constructing a database able to handle such graphical gene-expression data by mapping it onto 3-D reconstructions of mouse embryos whose tissues have been delineated. This article reviews the progress that has been made in this project and describes its two major components, CD-ROMs of the 3-D reconstructions to be held on the user's computer and a gene-expression database that will be maintained at a host site, the two being linked over the internet by a complex Java-based interface for submitting data and querying the database.Copyright 1997 Academic Press Limited Copyright 1997Academic Press Limited

Journal Article↗
PubMed1996

Characterization of Aeromonas hydrophila strains of clinical, animal, and environmental origin expressing the O:34 antigen.

A collection of Aeromonas strains of different origins were characterized for isolates expressing the O:34 somatic antigen. Of over 200 strains tested, approximately 14% belonged to serogroup O:34 with >85% of these strains identified as A. hydrophila regardless of source. A subset of 14 A. hydrophila O:34 strains were further analyzed for a number of structural and pathogenic features. Most O:34 strains expressed similar whole-cell protein profiles with regards to minor bands, but major band differences were noted in outer membrane proteins (OMPs) migrating between the 31K and 58K region. OMP profiles could be subdivided into three distinct patterns. All O:34 strains expressed a heterogeneous O polysaccharide side chain profile in their lipopolysaccharide (LPS), although some variation in the electrophoretic migration of lower and higher molecular weight LPS bands was noted. Polyclonal antisera raised against a 45-K OMP-associated protein of one O:34 strain (AH-195) reacted in immunoblot assays with a major 43 to 46-K OMP in 11 of 14 (79%) O:34 strains tested. Most O:34 strains (69%) were found to be pathogenic in mice with LD-50 values (i.p.) of <1.0 x 10(7) CFU; pathogenicity appeared to correlate best with elevated protease activity. The collective results suggest significant differences in both structural and pathogenic properties between some members of the O:34 group originating from human and nonhuman (fish, water) sources.

Aeromonas hydrophila↗
PubMed1996

Crisis intervention: program evaluation.

Crisis intervention is based upon crisis theory and is defined as a short-term active mode of therapy that focuses on solving the client's immediate problem and reestablishing psychological equilibrium. The crisis intervention program was the first phase in the development of a broader mental health program with advancement decisions being based upon evaluation results of this initial phase. An evaluation methodology using the Stufflebeam Goal-Stakeholder Model (1980) was designed and implemented. A satisfaction survey was conducted to develop a database relative to the program's process. The Mental Health Category Measure, and the Crisis Call Outcome Rating Scale were used to capture outcome data. Analysis of the qualitative and quantitative data indicate that stakeholders are satisfied with the program. outcome data demonstrates that the program produces the intended outcomes. Triangulation, a method of comparing the qualitative and quantitative findings revealed consistency, and thus provides confidence in the accuracy of the findings.

Adolescent↗
PubMed1995

Probes and polymerase chain reaction for detection of food-borne bacterial pathogens.

DNA-hybridization and the polymerase chain reaction (PCR) are techniques commonly used to detect pathogenic bacteria. In this paper, the use of these techniques for detection of Salmonella, E. coli, V. cholerae, non-O1 Vibrio, Yersinia enterocolitica, Campylobacter, Listeria monocytogenes, Staphylococcus aureus, Bacillus cereus, Clostridium perfringens, and C. botulinum is reviewed with emphasis on application in food microbiology. In food control, DNA-techniques have most often been used in a 'culture confirmation' fashion, i.e. bacteria are enriched and sometimes even purified by traditional culture procedures and thereafter identified by the use of DNA-based methods. The most desirable approach is, however, to detect organisms directly in the food, but major problems remain to be solved before this can be routinely performed.

Bacteria↗
PubMed1995

Application of automation to the detection of radiation damage using FISH technology.

A whole chromosome painting approach was employed to highlight the damaging effects of low-to-moderate doses of ionizing radiation. A detailed tally of damage involving the painted chromosomes 1 and 2 was compiled from visual analysis and compared with the results of an automatic image processing approach, where the possible outcomes were 'normal', 'abnormal', or 'rejected'. The performance of the automatic approach was tested using a set of 9000 bicolour metaphase images harvested from whole-blood cell culture following irradiation levels of 0.0, 0.5, 1.0 and 2.0 Gy. Every metaphase image in the set was analysed visually. The automatic analysis model was based on two simple image criteria to distinguish normal from abnormal; either an increase in the number of painted objects or a large asymmetry in the area distribution of the expected number of painted objects. A result was obtained without a full karyotype analysis. In practice, automatic analysis produced a set of images for review that were enriched by a factor of 3-4 in true abnormal images. Fast visual review of these images (approximately 200/h) selected the true abnormals. A comparison of the automatic analysis with the visual analysis showed that automated analysis correctly identified 60% of normal cells, 59% of abnormal cells and 73% of rejected cells.

Adult↗
PubMed1994

Automatic fluorescence metaphase finder speeds translocation scoring in FISH painted chromosomes.

A fluorescence metaphase finder was constructed with commercially available hardware and a standard Unix workstation. Its accuracy was measured in terms of the number of false positive and false negative detected metaphases on a variety of different slide preparations. The metaphase finder was used in a translocation scoring experiment in which metaphase preparations of human peripheral blood lymphocytes were hybridized with whole chromosome probes to chromosomes #1, #2, and #4. The automatic finder presented metaphases to the cytogeneticist, centered in the eyepieces at x63. The cytogeneticist's scores of analyzable metaphases and of painted chromosomes involved in rearrangements were recorded. The time for the analysis was recorded and compared to the time to analyze a similar number of cells in a purely visual experiment in which the cytogeneticist scanned for cells and analyzed them, both at x63. The results showed that, neglecting the machine time spent scanning unattended, the amount of time required for the analysis was reduced by a factor of three. Furthermore, in this experiment the metaphase finder found more scorable metaphases than the cytogeneticist found by visual scanning. Machine-assisted scoring had additional, less quantifiable, benefits; notably that digital images of metaphases sometimes assisted the analysis of chromosome rearrangements, that cells could be revisited easily, and that the analysis was much less fatiguing.

Cytogenetics↗
PubMed1994

Cirrhosis in patients with rheumatoid arthritis receiving low dose methotrexate.

We describe three patients with RA who developed cirrhosis while taking low dose methotrexate (MTX). This report includes a review of the risk factors for cirrhosis occurring in association with MTX. Two of these patients were part of a prospective study to quantify changes in pericellular and total collagen in 76 patients with RA receiving low dose pulse MTX, giving a point prevalence of cirrhosis of 2.63%.

Aged↗
PubMed1993

Safety belt restraints and compartment intrusions in frontal and lateral motor vehicle crashes: mechanisms of injuries, complications, and acute care costs.

A 3-year prospective study examined 76 frontal (F) and 45 lateral (L) motor vehicle crash (MVC) patients with regard to seatbelt restraint use and occupant compartment contact and intrusion injuries. These 121 MVC victims with multiple injuries (39 belted [B] and 82 non-belted [NB]), admitted to a level I trauma center, were studied by accident reconstruction and medical data analysis. They had a MVC mean impact velocity (delta V) of 30 +/- 11 mph and an injury Severity Score of 29 +/- 12. Proper restraint use reduced brain injury in F MVCs (30% FB vs. 47% FNB) but had no effect in L MVCs (63% LB vs. 30% FB [p < 0.06]). Belt use did not protect against lung, liver, spleen, pelvis, or lower extremity (LE) injury. These appeared to be more a function of crash direction, with LE injuries higher in F crashes (p < 0.04) and pelvis injuries (p < 0.001) higher in L crashes. In FB crashes, however, properly used safety restraints were the primary cause of bowel or colon injuries (p < 0.006). Belts did not prevent thoracic or abdominal solid organ injuries in L crashes. Contact-intrusions (CI) of the car occupant compartment in F crashes were the main cause of brain (A-pillar), lung and liver (steering wheel and instrument panel), and LE (toepan) injuries; but in L crashes, side-door CI caused lung, aorta, liver, and pelvic injuries. In contrast, contact-only (CO) injuries of the steering assembly were mainly responsible for injuries to the lung, heart, and liver in F crashes, and side-door CO for lung, liver, and spleen injuries in L crashes. Deaths and complications after injury were higher among F MVC occupants, or when delta V was > or = 30 mph. Hospital and professional costs reflect the complex care needed for victims of multiple injuries: FB, $99,000; FNB, $95,000; LB, $75,000; LNB, $79,000; total, $10.7 million. Present vehicle safety standards are not adequate, and structural design changes are needed to improve restraints and protect occupants from intrusion-related injuries.

Abdominal Injuries↗
PubMed1991

Hepatic methotrexate content and progression of hepatic fibrosis: preliminary findings.

Liver tissue from 16 patients with rheumatoid arthritis was studied. The patients had received low dose methotrexate weekly for a minimum of 12 months between two liver biopsies. The progression of pericellular fibrosis was measured by computerised image analysis. Extracts of these liver biopsy specimens were pooled into five samples according to the progression of hepatic fibrosis and analysed by high performance liquid chromatography. The concentrations of methotrexate, 2,4 diamino-N(10)-methylpteroic acid, and methotrexate polyglutamate were markedly increased in the samples obtained from the three patients who recorded the greatest increase in fibrosis. These preliminary data suggest that progression of hepatic fibrosis is related to the retention of methotrexate and metabolites in the liver.

Adult↗
PubMed1990

[Interferon alfa-2B in chronic lymphatic leukemia of the B-cell type].

In a clinical phase II study nine patients (five men and four women; mean age 48 [42-58] years) in an early stage of chronic lymphatic leukaemia (CLL) of the B-cell type were treated with recombinant alpha-2b interferon (IFN alpha-2b), initially at a dosage of 5 mega units subcutaneously three times weekly, but in some cases reduced to 2.5 or raised to 10 mega units. Duration of treatment has been 15-36 months. Through-flow cytometry in seven patients demonstrated a definite fall in circulating B1-positive lymphocytes. Lasting partial remission (duration of 106-134 weeks) was achieved in four patients, in a further four the condition remained stable. A recurrence was noted in the patient with the initially highest lymphocyte count (52,000/microliters) after 28 weeks, control being achieved only after 64 weeks of chemotherapy. Side effects were flu'-like symptoms and (in two instances) depression. In three patients there was a clear rise in serum immunoglobulin concentrations as sign of IFN alpha-2b-induced increased immune response, while in four HLA-DR expression on monocytes was doubled. It is concluded that early treatment of CLL with IFN alpha-2b may delay the onset of necessary chemotherapy, any antibody-deficiency may be improved and survival time may ultimately be lengthened.

Adult↗