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Biomedical subjects

R Goodwin

Publications and source records attributed to R Goodwin.

At least 19 recordsLinked to original sources

The 'Queen Square bladder stimulator': a device for assisting emptying of the neurogenic bladder.

OBJECTIVE: To describe the effectiveness of a vibrating device for emptying the neurogenic bladder in patients with neurological disease. PATIENTS AND METHODS: The study involved 36 patients, comprising 29 with multiple sclerosis (MS), four with multiple system atrophy (MSA), one with radiation myelitis and two with neurological disease of uncertain aetiology. Most patients with MS (27) were able to walk unaided or with aids. Three of the 36 patients had loss of suprapubic sensation (two MS, one with uncertain diagnosis). All patients had free flow rates and ultrasonographic post-void residual volumes (PVRs) measured before and after voiding while using a vibrating device (frequency 60 Hz) applied to the suprapubic region. They also completed questionnaires about their urinary symptoms before and after the continued use of this device. The mean follow-up was 11.5 months (range 8-14). RESULTS: The device improved the symptoms in 25 of 36 patients (70%) and reduced the PVR from a mean (standard deviation) of 175 (78) mL to 68 (32) mL. It was not useful in patients with PVRs of > 400 mL, Kurtzke pyramidal function scores of > 3, and in those with suprapubic numbness. There were no complications and most patients complied well. CONCLUSIONS: Suprapubic vibration is an effective means of emptying the neurogenic bladder in patients who are not severely disabled and who have detrusor hyper-reflexia. It probably acts through a tonic vibration reflex which is under supraspinal influence. This device may be a useful alternative to clean intermittent self-catheterization.

Follow-Up Studies

The developmental genetics of hybrid inviability: a mitotic defect in Drosophila hybrids.

We report studies of the developmental basis of hybrid inviability in the Drosophila melanogaster complex. The pathology of these hybrids closely resembles that of mitotic mutants in D. melanogaster. We use mosaic and cytological analyses to show that hybrid male inviability is associated with, and probably caused by, a defect in mitotic cell division. In the mosaic study, we find that male clones produced in otherwise female hybrids are not cell lethal but are very small, probably reflecting defects in mitotic proliferation. Cytological inspection of larval neuroblasts reveals a profound mitotic defect in hybrids: chromosomes show a near-complete failure to condense even after 2 hr of incubation in colchicine. Both the defect in clonal proliferation and in chromatin condensation are rescued by mutations known to rescue normally inviable hybrid males. We present a simple model in which hybrid inviability is partly or entirely caused by a mitotic defect; this defect is, in turn, caused by an interaction between the Hybrid male rescue (Hmr) locus of D. melanogaster and autosomal gene(s) from D. melanogaster's sister species.

Animals

Comparison of a standard and a sensitive thromboplastin in monitoring low intensity oral anticoagulant therapy.

The greater precision in prothrombin time monitoring obtained using thromboplastins with low international sensitivity index (ISI) values are believed to result in improved patient care. The authors conducted a blinded prospective study of 84 random patients on low-intensity warfarin therapy who were monitored with either a sensitive (ISI, 1.3) or standard (ISI, 1.9) thromboplastin. For the patients monitored with standard and sensitive thromboplastins, respectively, no difference was found in the degree of anticoagulation (standard thromboplastin mean INR, 2.4 vs. 2.5, P = .37; sensitive thromboplastin mean INR, 2.6 vs. 2.6, P = .74; mean daily warfarin dose, 5.1 vs. 4.7 mg, P = .28) or efficacy (warfarin dosage adjustments, 117 vs. 116; clinic visits, 362 vs. 378; percentage of therapeutic INR determinations, 47% vs. 48%). In addition, no difference was found in bleeding prevalence or severity (.22 vs. .27 events per person-year observation). The authors concluded that monitoring anticoagulant therapy in the INR range of 2-3 with a standard thromboplastin may be comparable to monitoring with a more sensitive thromboplastin with respect to efficacy, safety, and degree of anticoagulation achieved.

Administration, Oral

Improved rapid photometric assay for quantitative measurement of PMN migration.

We developed an improved quantitative method to measure in vitro polymorphonuclear leukocyte (PMN) migration using an assembly consisting of a 96-well chamber, polycarbonate filter membrane, and a 96-well microtiter plate. The convenience in setup and counting of migrated cells using this method allows processing of 80 samples and 16 controls in a short assay time of only 2 h. The peroxidase contained in PMNs was used as a marker enzyme to determine the number of migrated cells. Peroxidase released from lysed migrated cells was detected with an enzymatic method utilizing o-dianisidine as substrate. Photometric measurement was performed with a conventional microtiter plate reader at a wavelength of 405 nm. Optical density readings obtained using the enzymatic assay correlated with the number of migrated cells in a linear fashion up to 1 x 10(5) cells/well. The sensitivity of the enzymatic assay was sufficient to determine cell counts as low as 500 PMNs. PMNs lost no measurable amounts of peroxidase during the migration assay when ZAS was used as the chemoattractant. A calibration method was developed to make corrections for variations in the peroxidase content of different cell preparations and changes in the peroxidase content of cells exposed to the chemoattractant. High speed, convenient handling, and the use of standard laboratory equipment result in low cost per assay and make this migration assay ideally suited to research and clinical applications.

Cell Migration Inhibition

Whose choice?

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Choice Behavior

Immortalization of murine B cells in vitro with oncogene-containing retroviral vectors.

A large panel of oncogene-containing retroviral vectors has been constructed and used to infect activated murine splenic B cells to determine whether particular oncogenes are capable of directly mediating B cell immortalization. Mature B cell lines have been consistently established with some of these retroviral vectors. These B cell lines arose at a low frequency, indicating that more genetic events were required in addition to infection with the retroviral vector for immortalization to occur. All such lines were LPS-dependent and non-tumorigenic. All lines secrete IgG and express surface IgG, but not IgD or IgM. In addition, they are CD11b+ and CD23-. These cells may be derived from the CD5 "lineage" or a related B cell subset and appear to be more susceptible to immortalization than conventional B cells.

Animals

Seroprevalence of antibodies to hepatitis C virus in high-risk hospital personnel.

OBJECTIVE: To estimate seroprevalence of antibodies to hepatitis C virus in healthcare workers at high risk for blood exposure. DESIGN: A prospective anonymous seroprevalence survey of 243 healthcare workers. SETTING: A large referral hospital and 2 community hospitals in Connecticut. PARTICIPANTS: Healthcare workers, including surgical personnel, dentists, hemodialysis workers, laboratory workers, and emergency room staff. RESULTS: Antibody to hepatitis C virus was found in 1.6% (95% confidence interval [CI95] = 0-3.2%) of healthcare workers. None of the prevalent seropositives had a past history of clinical hepatitis or blood transfusion. CONCLUSIONS: We conclude that the seroprevalence of hepatitis C virus in healthcare workers with a high degree of blood exposure is low and is similar to seroprevalence rates reported for volunteer blood donors. However, first-generation hepatitis C serologic tests may underestimate the true prevalence of infection. Further studies, including prospective cohort studies, will be required to determine if the low seroprevalence is from low risk of acquisition of disease or from loss of measurable humoral antibody response to the virus.

Adult

Chromosomal location of the human tumor necrosis factor receptor genes.

TNFR1 and TNFR2, the genes encoding the two forms of the human tumor necrosis factor receptor, were localized to normal human chromosomes by in situ hybridization and Southern blot analysis of a series of human x mouse hybrid cell lines. TNFR1 maps to 12p13 and TNFR2 maps to 1p36.

Blotting, Southern

Interleukin-7 is a growth factor of precursor B and T acute lymphoblastic leukemia.

We investigated the proliferation-inducing effects of human recombinant interleukin-7 (IL-7) on acute lymphoblastic leukemia (ALL) cells. It is shown that IL-7 stimulates DNA synthesis in ALL cells of B-cell precursor (n = 5) as well as immature T-cell origin (n = 2). Cytogenetic analysis of the cells of four patients proliferating in IL7-supplemented cultures established the leukemic descendence of the IL-7-responsive cells. 125I-IL-7 binding experiments with the cells of one patient and with two ALL cell lines showed the presence of two types of IL-7 receptors: one with a high affinity (kd 29 to 51 pmol/L) and one with a low affinity (kd 2.3 to 76 nmol/L) for the ligand. We conclude that IL-7 is one of the cytokines involved in the complex regulation of ALL cell proliferation.

B-Lymphocytes

A multiwell cell settling and adherence chamber for morphology and differential counting.

A simple multiwell chamber is described that can be used to prepare randomly distributed cells on a microscope slide, suitable for morphological identification and differential counting. To the eight wells of the chamber are added 50-microliter volumes of cell suspension at concentrations of 10(3)-10(6) cells/ml. As the cells settle, fluid is slowly wicked away by a damp filter paper sandwiched between the microscope slide and the acrylic top plate of the multiwell chamber. Within 20-40 minutes, the cell monolayers on the slide are completely dry. The combined settling and bulk fluid removal results in a distribution of adherent cells that are sufficiently spread to exhibit excellent morphology after staining. If the chamber is centrifuged for 30 seconds at 50x g immediately after addition of cells, recovery of cells in the monolayer is virtually 100%, and as few as 50 input cells per 50 microliters can be detected. Agreement between predicted and observed differential counts of cell mixtures indicates that cells in the monolayer were distributed randomly.

Cell Adhesion

Murine thymocytes proliferate in direct response to interleukin-7.

The ability of interleukin-7 (IL-7) to stimulate murine thymocyte proliferation was investigated. IL-7, either alone or in concert with lectin, induced proliferation of adult thymocytes as well as day 13 fetal and adult CD4-/CD8-thymocytes. The IL-7-induced proliferative response of unfractionated thymocytes could not be inhibited by antibodies to IL-2, or IL-4, IL-6, or the IL-2 receptor. In addition, IL-2, IL-4, and IL-6 were not produced by thymocytes activated with IL-7, as judged by the absence of biologically active cytokine in IL-7-stimulated culture supernatants. IL-7 could act in concert with IL-2 and IL-4 or with IL-4 to enhance the proliferative response of thymocyte cultures. Thus, IL-7 may cause proliferation of thymocytes directly, not indirectly, through production of IL-2, IL-4, or IL-6. IL-7 may then play a significant role in differentiation of T lymphocytes.

Adjuvants, Immunologic

Inhibition of vaccinia RNA guanine 7-methyltransferase by compounds designed as multisubstrate adducts.

Several potential inhibitors of mRNA guanine 7-methyltransferase, which were designed from mechanism-based considerations, were evaluated against the vaccinia virus capping enzyme complex. Of the compounds tested, 5'-deoxy-5'[6-(2-aminopyrrolo[2,3-d]-pyrimidine-4-one) methylthio]adenosine (9) had good selective inhibitory activity against vaccinia mRNA guanine 7-methyltransferase, exhibiting an IC50 of 9.2 X 10(-5) M. Structure-activity considerations suggest that specific inhibition of RNA methyltransferases by low molecular weight multisubstrate adduct inhibitors may be achievable.

Chemical Phenomena

Community phase of cardiac rehabilitation.

Although their effects cannot be shown to statistically alter coronary heart disease mortality or morbidity, voluntary health organizations throughout the world clearly play an important role in bringing about favorable changes in the natural history of this disease and in the community phase of its management. In particular, voluntary organizations are able to conduct research surveys and field trials and by so doing favorably influence state health administration. They are able to correct temporary deficiencies in health services, particularly in the form of psychosocial support and cardiac health education. Observers note that the major change in community phase management has occurred with the wider use of coronary bypass surgery since 1975. More objective data, especially relating to psychosocial factors, can be expected when further research (especially the MONICA Study) is completed. Throughout the world, however, existing voluntary health organizations could be more active in the community phase of cardiac rehabilitation. It would seem an area where such organizations could well do more. A challenging question that should be constantly reviewed is 'Can we do more to reduce the effects of invalidism in cardiac patients?'

Australia

The MMPI in three groups of patients with significant weight loss.

Fifty patients with severe weight loss thought to be caused by anorexia nervosa were hospitalized for evaluation. On the basis of psychiatric history and mental state examination, they were divided into three diagnostic categories: anorexia nervosa; other. The MMPI of patients with anorexia nervosa was markedly abnormal, with highest peaks on the D (depression), PT (obsessionality and anxiety), and SC (schizophrenia) scales. This profile was similar to that of patients with obsessional symptoms and neurotic depression, but differed significantly from the profile of patients with low weight but normal mental state examination. These findings suggest that starvation alone does not explain the psychopathological symptoms similar to those with depressive and obsessional symptomatology. The MMPI is useful in differentiating anorexia nervosa from those with lowered weight from nonpsychiatric causes, but does not by itself provide a distinct diagnostic category when compared with neurotic disorders having similar symptom clusters.

Adult

Menetrier's disease in children.

Two new cases of Menetrier's disease in children are reported. The ten cases of this protein-losing gastropathy previously reported in the literature are reviewed. Clinical presentations, laboratory findings, possible causes, and comparison with the adult form of Menetrier's disease are discussed. Menetrier's disease in children may be more common than reported, as its symptoms are usually transient. The prognosis in children is excellent; therefore the distinction between Menetrier's disease in children and other protein-losing enteropathies is vital.

Child, Preschool

Controlled sedation with alphaxalone-alphadolone.

Alphaxalone-alphadolone (Althesin), diluted and administered as a controlled infusion, was used as a sedative for 30 patients in an intensive therapy unit. This technique allowed rapid and accurate control of the level of sedation. It had three particularly useful applications: it provided "light sleep," allowed rapid variation in the level of sedation, and enabled repeated assessment of the central nervous system.Sedation was satisfactory for 86% of the total time, and no serious complications were attributed to the use of the drug. Furthermore, though alphaxalone-alphadolone was given for periods up to 20 days there was no evidence of tachyphylaxis or delay in recovery time.

Adult