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Biomedical subjects

J Low

Publications and source records attributed to J Low.

At least 37 records · Page 2Linked to original sources

Unpacking the black box of therapy -- a pilot study to describe occupational therapy and physiotherapy interventions for people with stroke.

OBJECTIVE: To describe the components used in the practice of occupational therapy and physiotherapy for people with stroke and to examine variability between services. DESIGN: A time-sampling strategy in which therapists recorded their face-to-face interventions with stroke patients during 12 weeks over a total of 17 months. SETTINGS AND SUBJECTS: Six occupational therapists and seven physiotherapists from four services (three day hospitals and one domiciliary stroke rehabilitation service) recorded interventions with 89 stroke patients recruited to a larger randomized controlled trial. MAIN OUTCOME MEASURES: Frequencies of use of interventions, together with other details about delivery of therapy, were recorded using a data collection booklet and coding system designed by the participating therapists. RESULTS: The median treatment time for a session was 45 minutes. The most frequently recorded components of physiotherapy intervention were 'walking', 'standing balance' and 'upper limb movement pattern', and of occupational therapy 'physical function', 'social and leisure activities' and 'other'. There was variability between the services in terms of median treatment time, use of intervention codes, frequency of treatment sessions, amount of time spent working with assistance and amount of group work. CONCLUSIONS: The findings support the view that occupational therapy and physiotherapy with people with stroke are not homogeneous activities, and vary between therapists and services. Recommendations include further development of the tool, and use of other methodologies to explore the process and nature of stroke rehabilitation.

Aged↗

Acetabular fractures. Clinical outcome of surgical treatment.

Sixty patients with acetabular fractures were treated surgically. All fractures were a result of high energy trauma, most with significant associated injuries. Fifty-three of the patients were followed up for at least 2 years. Clinical outcome was analyzed clinically using the Harris hip score and radiographically. In 41 (77.4%) of the patients, the surgical procedure was judged successful (Harris hip score greater than 80 points). Three factors were found to be statistically significant predictors of such an outcome: patient age younger than 40 years; simple fractures based on the classification of Letournel and Judet; and absence of damage to the femoral head. Possible influential factors that were not found to be statistically significant in this population included additional injuries, immediate complications, quality of reduction, heterotopic ossification, ipsilateral femoral fracture, and sciatic nerve damage. Open reduction and internal fixation of the displaced acetabular fracture, although a demanding procedure, can result in a satisfactory clinical outcome given a consistent approach with a dedicated team.

Acetabulum↗

Inhibition of red cell aggregation prevents spontaneous echocardiographic contrast formation in human blood.

BACKGROUND: Spontaneous echocardiographic contrast (SEC) is a pattern of blood echogenicity that has been attributed to ultrasonic backscatter from blood cell aggregates that form under low shear conditions. Patients with left atrial SEC have an increased thromboembolic risk. This study examined the role of red cell and platelet aggregates in the pathogenesis of SEC in human blood and the effects on SEC of antithrombotic therapy and red cell disaggregatory agents. METHODS AND RESULTS: Blood echogenicity was examined with the use of quantitative videodensitometry over a controlled range of flow velocities in an in vitro model characterized by nonlaminar flow conditions. One hundred ninety study samples were prepared from single fresh blood donations (40 to 120 mL) from 24 healthy volunteers and 11 patients. Whole blood echogenicity was unaltered by depletion of platelets, stimulation of platelet aggregation with adenosine diphosphate, or inhibition of platelet aggregation with aspirin. Low flow-related echogenicity increased with increasing hematocrit (P<.001) but was abolished when red cells were lysed selectively with saponin (P<.001). In the presence of red cells, low flow-related echogenicity increased with increasing fibrinogen concentration (P<.001) and with plasma paraproteins. Low flow-related echogenicity in whole blood was unaltered by heparin and warfarin but was reduced in a dose-dependent manner by dextran 40 (40 mg/mL, 70% reduction, P<.001) and poloxamer 188 (8 mg/mL, 47% reduction, P<.001), which inhibited red cell aggregation. CONCLUSIONS: These results support protein-mediated red cell aggregation as the mechanism of SEC in human blood. Inhibition of red cell aggregation, indexed by resolution of SEC, may provide an alternative to anticoagulant and antiplatelet therapy to reduce cardiac thromboembolic risk.

Adult↗

An automated high capacity data capture and analysis system for the in vitro assessment of leukocyte adhesion under shear-stress conditions.

Parallel-plate flow chambers have been used to model the vascular microcirculation and study the in vitro dynamic adhesive interactions of leukocytes and human umbilical vein endothelial cells (HUVECs). We describe here a high capacity system which can simultaneously monitor the adhesive interaction of neutrophils and HUVECs in ten flow chambers. Automated data collection was achieved with an image analyzer controlling the autostage and autofocus attachments of an inverted microscope. Images from the flow chambers were captured via phase-contrast microscopy using a video camera and laser videodisk recorder. The images were downloaded off-line into an image analyzer for automated counting of rolling and adherent cells. Neutrophils were detected by their "phase bright' characteristics. An automated optimization procedure allowed the computer to choose the best setting for the selective detection of neutrophils. In addition, a method which utilized image averaging was used to distinguish between rolling and adherent cells. A comparison of the results obtained from the manual and automated counting methods revealed linear relationships for the counting of both adherent (r = 0.98) and rolling cells (r = 0.96) with counting efficiencies of 59% and 46%, respectively. The utility of the system was demonstrated by its ability to measure the adhesive interaction between neutrophils and HUVEC in response to stimulus such as interleukin-1 alpha (IL-1 alpha), histamine, or formyl-1-methionyl-1-leucyl-1-phenylalanine (fMLP). In conclusion, we have developed an automated assay which combines the capacity of ten flow chambers with a computerized data analysis system; the result is an efficient and reproducible assay which minimizes operator associated errors and biological variability.

Cell Adhesion↗

Phase I trial of a novel matrix metalloproteinase inhibitor batimastat (BB-94) in patients with advanced cancer.

Degradation of basement membrane and extracellular matrix by matrix metalloproteinases (MMPs) is believed to be required for tumor invasion, tumor-induced angiogenesis and vascular invasion. A synthetic hydroxamate, batimastat (also known as BB-94), inhibits MMPs by binding the zinc ion in the active site of the MMP. Batimastat inhibits at least 50% of MMP activity at concentrations less than or equal to 10 ng/ml in vitro. Batimastat retarded ascites accumulation and increased survival in mice with human ovarian tumor xenografts. Acute and long-term toxicological studies revealed no major toxicity in animals. Batimastat is poorly soluble and was administered intraperitoneally (i.p.) as a suspension. Previous studies in patients with malignant ascites have shown no major toxicities at doses as high as 1350 mg/m2.

Adult↗

Anti-invasion drugs.

Most of the pharmaceuticals in clinical practice today for treatment of breast and other cancers are cytotoxic or cytostatic inhibitors of tumor growth. While this type of drug has found its place, along with surgery and radiotherapy, in treatment of disease, the breast cancer death rate has not decreased. This appears to be the result of rising incidence, resistance to therapy, and metastasis of the disease. Since distant metastasis (usually indicated by lymph node involvement) of breast cancer is related only indirectly to tumor size, it would appear that a concerted effort should be made to discover drugs which directly interfere with this complex process. Metastasis appears to depend upon tumor cell motility, dedifferentiation, local invasion, and angiogenesis. Significant progress has been recently made in the creation of new animal models of metastasis and in identifying several new drugs which may be suitable for clinical inhibition of this process. This article reviews current findings on anti-invasion/metastasis drugs with a focus on breast cancer.

Animals↗

The concept of hardiness: a brief but critical commentary.

This paper is a brief critique of the concept of hardiness. While the concept is appealing in its potential to elucidate the relationships between stress, health and illness, I argue that there are problems with how the concept is defined, measured and applied. In particular, the usefulness of the concept is diminished through class and gender bias.

Chronic Disease↗

Dissemination and tissue invasiveness in murine acute leukemia associated with acquisition of p53 mutation and loss of wild-type p53.

Approximately 60% of mice treated with split-dose radiation develop leukemias that disseminate widely through the body, whereas 40% of the treated mice incur leukemias that are contained entirely within the thymus. We studied the status of p53 in non-cultured samples of thymic leukemias and in cell lines established from these leukemias. In those mice with disseminated disease, primary samples were also obtained from visceral leukemic organs, and cell lines were established from these leukemic organs for further study. Using single-strand conformation polymorphism (SSCP), nucleic acid sequencing, and immunochemical analysis, we found that mutation of both p53 alleles occurred in leukemic cell lines developed from nine of 10 disseminated leukemias; mutation of one p53 allele with the other remaining wild-type occurred in one disseminated leukemia. A p53 mutation unique for each mouse was found in all cell lines established from the different leukemic organs of each mouse. The same mutation was also found in the non-cultured leukemic tissues of each mouse, indicating that the mutations originated in vivo and were clonal. Seven of seven non-disseminating thymomas possessed wild-type p53 only. Hence, in vivo dissemination and tissue invasiveness were associated with the loss of wild-type p53 by mutation of both alleles or by mutation and loss of heterozygosity, as revealed by studies of cell lines established from them. The selective in vivo dissemination of leukemia cells possessing p53 mutations had a parallel in vitro. Leukemia cell lines from mice harboring disseminating leukemia were established more readily (success rate greater than 80%) than lines from mice harboring thymic nondisseminating leukemia (success rate less than 10%). Additionally, while mice with disseminating leukemia harbored a mixture of wild-type and mutant p53-encoding thymoma cells, only cell lines possessing mutant p53 became established in culture. Mutations found in thymoma cell lines were always detectable by SSCP and sequencing of DNA extracted from non-cultured thymoma tissue. However, in non-cultured leukemic tissue of visceral organs, the clonal p53 mutations found in cell lines established from them were often not detectable by SSCP or sequencing but were detectable by immunochemical analysis or polymerase chain reaction amplification. This indicates an unexpected degree of masking of mutant genes by wild-type genes present in the leukemic tissue. Masking was evident even in leukemic organs that were grossly larger than normal organs. Hence, routine screening of leukemic tissue by SSCP and sequencing may result in a highly significant underestimation of the incidence of p53 mutations.(ABSTRACT TRUNCATED AT 400 WORDS)

Alleles↗

Cytoprotective effects of CI-959 in the rat gastric mucosa: modulation of leukocyte adhesion.

BACKGROUND & AIMS: CI-959 is an anti-inflammatory agent that inhibits neutrophil adhesion, respiratory burst, and mast cell histamine release in vitro. In view of the emerging role of neutrophils in gastric erosive damage, the goals of this study were to assess the gastric cytoprotective effects of CI-959 and identify the mechanism responsible for this action. METHODS: Cytoprotective effects in the rat nonsteroidal anti-inflammatory drug and ethanol erosion models were assessed using image analysis. The in vivo effects of CI-959 on gastric acid secretion, arachidonic acid metabolism, and intracellular sulfhydryl and leukocyte adhesion were also examined. RESULTS: CI-959 protected prophylactically against the erosive damage induced by aspirin, indomethacin, and ethanol with 50% effective doses (ED50s) of 0.05, 1.0, and 0.07 mg/kg administered orally, respectively. When administered after indomethacin or ethanol, CI-959 had no effect on the healing of erosive damage. CI-959 did not alter gastric acid secretion, arachidonic acid metabolism, or intracellular sulfhydryl levels. In vivo, CI-959 blocked leukocyte adhesion in intravital microscopy studies using indomethacin (ED50, < 5 mg/kg orally) or platelet-activating factor (50% inhibiting concentration, approximately 10 mumol/L) as the adhesion stimulus. CONCLUSIONS: The most likely mechanism responsible for the cytoprotective effects of CI-595 is its inhibitory effects on leukocyte trafficking and/or adhesion.

Animals↗

Erythrocyte sedimentation rate studies in whole human blood.

Precise measurements have been made of the rate of sedimentation of whole blood in which the concentrations of red blood cells and the plasma proteins have been systematically varied. The contribution of each factor to the sedimentation process is expressed in terms of three parameters that describe the sedimentation curve: the set-up time, and the slopes of the first and second phases of settling. This analysis affords delineation between the onset and the degree of aggregation of the red blood cells as contributors to the usual ESR value, the height of plasma in a 200 nm blood column after 60 min. In terms of the 60 min ESR value, an increase in the haematocrit or albumin concentration inhibits sedimentation, the latter only slightly, whereas an increase in the concentration of globulin or fibrinogen accelerates sedimentation, with fibrinogen showing the more marked effect.

Blood Proteins↗

Gain-of-function mutations of the p53 gene induce lymphohematopoietic metastatic potential and tissue invasiveness.

Leukemia cell infiltration and the induction of lethal hematopoietic disease in immune-deficient SCID mice transplanted with human T cell acute lymphoblastic T leukemia (T-ALL) cells occurred only when the cells possessed mutant p53 genes and lacked a wild-type allele or when T-ALL cells lacking p53 protein were infected with specific mutant p53 genes. A series of six mutant p53 genes were cloned from relapse T-ALL-derived cell lines and were constructed into defective retroviral expression vectors. Viruses encoding mutant p53 proteins were used to infect relapse T-ALL cells in a study designed to compare their pathogenic potency. The mutant p53 genes possessed a distinct hierarchy in vivo and in vitro: mutants inducing the greatest increase in proliferation of different T-ALL lines in vitro and colony formation in methylcellulose cultures also induced tissue invasiveness of infected T-ALL cells in vivo. Mutant p53 gene transfer to a cell line lacking p53 protein showed that the more potent p53 mutants possessed a distinctive dominant oncogenic activity in vitro and in vivo. The dominant oncogenic activity of these mutant p53 proteins was not dependent on the presence of and on complex formation with wild-type p53 protein. These "hot" p53 mutations thus represent bona fide gain-of-function mutations. Infection of p53-negative T-ALL cells with viruses encoding gain-of-function mutant p53 genes resulted in the acquisition of metastatic potential and tissue invasiveness. Taken together, our results suggest that specific mutant p53 genes play a role in the generation of lymphohematopoietic metastatic potential and tissue invasiveness as assayed in SCID mice, whereas the expression of wild-type p53 is capable of keeping this metastatic potential in check.

Animals↗

Characterization of a new allele of the human ERBB2 gene by allele-specific competition hybridization.

Nucleotide sequence analysis of the ERBB2 proton-oncogene in human breast tumors revealed a sequence variation at codons 654 and 655, corresponding to the transmembrane region of the protein. To investigate this polymorphism, genotyping of 340 unrelated individuals was conducted by allele-specific oligonucleotide (ASO) hybridization of DNA amplified from the ERBB2 transmembrane region. ASO hybridization under competition conditions allowed rapid and unambiguous assignment of alleles and revealed the occurrence of a new allele, B3, encoding Val-Val. The sensitivity and the specificity of the ASO competition hybridization technique indicate that the method is generally applicable to the analysis of polymorphisms in the human genome.

Alleles↗

Chart tracking systems: prerequisite to medical records automation.

In summary, automation of chart tracking is the place to begin full-scale medical record automation. Its collected data provides the framework for design and implementation of other systems, frees resources to use data to best advantage, and allows employees to make a comfortable transition from manual methods to computerized charts. A properly designed tracking system is the first step on the path to the electronic medical record.

Hospital Bed Capacity, 500 and over↗

Clinical experience with the Silc Cup Vacuum Extractor.

The relative merits of vacuum extraction have been extensively studied and its advantages analysed. These include its ease of application, encouragement of "autorotation" of the malpositioned foetal head and its safety for both foetus and especially the mother. One hundred and eighty-six vacuum extraction assisted deliveries were performed at the Department of Gynaecological Oncology & Urology, Kandang Kerbau Hospital, from 1988 to 1990 using the 50 mm Silicone Silc Cup Vacuum Extractor (Menox AB). Anaesthetic requirements were minimal with 97% of cases accomplished with local perineal anaesthesia. Maternal complications were very few and only 1.6% of cases had third degree lacerations. There was no maternal or foetal mortality. The most frequent foetal morbidity was neonatal jaundice (28%) with only 7% requiring phototherapy. Cephalohaematoma was found in 8% and 2% had minor scalp abrasions. There were 3 infants with subaponeurotic haematoma who subsequently recovered uneventfully. Vacuum deliveries that were attempted but completed by forceps deliveries ("failed" vacuum extraction) accounted for 10% of total cases. The Silc cup vacuum extractor although not a replacement for all forceps manoeuvres offers a safe and efficient method of assisted delivery under the appropriate clinical circumstances.

Adult↗

Case reviews in the family physician's office.

The majority of patients with emotional or psychiatric disorders are treated in the primary care setting without psychiatric input. Psychiatrists need to find ways of helping family physicians manage these patients without necessarily taking over their care. One way of achieving this is for a psychiatric consultant to visit the family physician's office on a regular basis to discuss the physician's problem cases. This paper describes such a pilot project, outlines the kinds of problems family physicians discussed and recommendations that were made, and discusses the benefits of this collaborative approach.

Community Mental Health Centers↗