Primary care groups. Alter ego.
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Administrative Personnel↗
Biomedical subjects
J Watson
Publications and source records attributed to J Watson.
ELAV proteins stabilize deadenylated intermediates in a novel in vitro mRNA deadenylation/degradation system.
We have developed an in vitro mRNA stability system using HeLa cell cytoplasmic S100 extracts and exogenous polyadenylated RNA substrates that reproduces regulated aspects of mRNA decay. The addition of cold poly(A) competitor RNA activated both a sequence-specific deadenylase activity in the extracts as well as a potent, ATP-dependent ribonucleolytic activity. The rates of both deadenylation and degradation were up-regulated by the presence of a variety of AU-rich elements in the body of substrate RNAs. Competition analyses demonstrated that trans-acting factors were required for RNA destabilization by AU-rich elements. The approximately 30-kD ELAV protein HuR specifically bound to RNAs containing an AU-rich element derived from the TNF-alpha mRNA in the in vitro system. Interaction of HuR with AU-rich elements, however, was not associated with RNA destabilization. Interestingly, recombinant ELAV proteins specifically stabilized deadenylated intermediates generated from the turnover of AU-rich element-containing substrate RNAs. These data suggest that mammalian ELAV proteins play a role in regulating mRNA stability by influencing the access of degradative enzymes to RNA substrates.
Adenosine Triphosphate↗
Mycophenolate mofetil, microemulsion cyclosporine, and prednisone as primary immunosuppression for pediatric liver transplant recipients.
Triple immunosuppressive therapy using mycophenolate mofetil (MMF), microemulsion cyclosporine (me-CsA), and prednisone offers the potential for potent immunosuppression without intravenous drug therapy or anti-T-cell antibody induction therapy. This report describes the application of an immunosuppressive protocol (CNp) using MMF, me-CsA, and prednisone as primary immunosuppression for pediatric liver transplant recipients at the University of California at San Francisco. From August 1995 through December 1996, 26 children (17 boys, 9 girls) aged 1 month to 16 years (mean +/- standard deviation, 58 +/- 62 months; median, 31 months) underwent liver transplantation at our institution, receiving CNp as primary immunosuppression. Posttransplantation renal function, incidence of leukopenia, and drug tolerance within the group receiving CNp as primary immunosuppression were compared with those of 19 children who received primary immunosuppression consisting of azathioprine, oil-based gel-encapsulated cyclosporine, and prednisone with anti-T-cell antibody induction therapy at the same institution from October 1993 through July 1995. No significant difference was observed between immunosuppressive protocols in serum creatinine level or incidence of leukopenia requiring medical therapy during the first year posttransplantation. Whereas gastrointestinal symptoms were observed in approximately 30% of CNp recipients during initial immunotherapy, tolerance of CNp primary immunotherapy was routinely achieved by the dose reduction of MMF. At 1 year posttransplantation, 20 children (77%) remained on CNp primary immunotherapy, 5 children (19%) were receiving tacrolimus-based immunotherapy secondary to rejection, and 1 patient (4%) converted to tacrolimus-based immunotherapy secondary to persistent gastrointestinal intolerance. In conclusion, CNp provides an alternative immunosuppressive protocol that eliminates the necessity of intravenous and induction immunosuppressive therapy with no increased incidence of posttransplantation renal dysfunction or leukopenia and is well tolerated in children.
Adolescent↗
Downregulation of apoptosis-related genes in keloid tissues.
BACKGROUND: Physiologically programmed cell death or apoptosis occurs during the natural balance between cellular proliferation and demise. MATERIALS AND METHODS: We compared the expression of 64 apoptosis-related genes in keloids and normal scars to investigate the potential role of apoptosis in keloid formation. Two sets of mRNA were isolated from keloids excised from four previously untreated patients and four normal scar patients separately. Human cDNA arrayed hybridization was performed to compare the apoptosis-related gene expression between these two groups. In addition, TUNEL assays were performed to evaluate the percentage of apoptotic cells in keloids (center and periphery) versus normal scars. RESULTS: Eight of the sixty-four apoptosis-related genes studied were significantly underexpressed in keloid tissue. The underexpressed genes and their relative expression compared with normal scar were defender against cell death 1 (DAD-1) (34.1% of normal scar); nucleoside diphosphate kinase B (c-myc transcription factor) (24.7%); glutathione S-transferase (17.9%); glutathione S-transferase microsomal (28.1%); glutathione peroxidase (47.2%); tumor necrosis factor receptor 1-associated protein (TRADD) (51.0%); 19-kDa interacting protein 3 (NIP3) (36.0%); and cytoplasmic dynein light chain 1 (HDLC1) (47.7%). Spatial analysis of apoptosis using TUNEL assays revealed apoptosis indices of 0.83 for keloid periphery and 0.63 for keloid center. CONCLUSIONS: In this study we demonstrated underexpression of apoptosis-related genes in human keloid tissue and decreased apoptotic activity in fibroblasts derived from keloids versus normal scars. We hypothesized that keloid fibroblasts fail to undergo physiologically programmed cell death and, thus, continue to produce and secrete connective tissue beyond the period expected in normal scar formation, accounting for the progressive and hypertrophic nature of keloids. This mechanism leads to new possibilities for treatment of keloids through induction of apoptosis.
Adolescent↗
Biodialysis: a new liver support system.
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Amino Acids↗
The best defense against hypoglycemia is to recognize it: is caffeine useful?
Caffeine, 1,3,7trimethylxanthine, is used by 80% of the adult population of the world in its various forms. Even the simple pleasure of consuming this socially acceptable drug has implications for the person with diabetes mellitus. Caffeine may increase an individual's sensitivity to hypoglycemia through the combined effects of reducing substrate delivery to the brain via constriction of the cerebral arteries, whilst simultaneously increasing brain glucose metabolism and augmenting catecholamine production. This article summarizes the evidence supporting the hypothesis that caffeine influences the perception of and physiological response to hypoglycemia. Under laboratory conditions, acute ingestion of caffeine markedly enhances the symptomatic and sympathoadrenal responses to hypoglycemia in both healthy volunteers and patients with type 1 diabetes. Recently a study of free-living people with type 1 diabetes showed that caffeine consumption increased the awareness of hypoglycemia. Caffeine has been associated with a number of negative effects and addiction. Most serious of these associations are ischemic heart disease and hypertension, the relationships have not been clearly established and the evidence to date is controversial. Thus we conclude that in modest doses, caffeine may be a useful adjuvant therapy for patients with hypoglycemia unawareness. For once here is a therapy which is inexpensive, safe, and remarkably popular with its consumers.
Adult↗
Out-patient parenteral antimicrobial therapy--a viable option for the management of cutaneous leishmaniasis.
Cutaneous infection with Leishmania braziliensis complex requires treatment with parenteral pentavalent antimonials to prevent development of mucocutaneous leishmaniasis. Patients with imported disease are usually managed in hospital because of concerns over drug toxicity. This study describes the clinical features and outcome of infection treated in the UK in an out-patient setting. Thirteen marines (aged 19-35 years) who acquired leishmaniasis in Belize were studied prospectively. Three had at least two lesions (0. 6-3 cm diameter), eight had regional lymphadenopathy and one had localized painless lymphatic thickening. Histology for amastigotes and PCR for Leishmania braziliensis complex was positive in all. Culture was positive in six. Patients received 1.5-2 g (mean 1.7 g) (20 mg/kg) sodium stibogluconate intravenously daily for 20 days. All developed transient musculoskeletal symptoms and asymptomatic hepatitis. Eleven developed biochemical pancreatitis, and one thrombocytopenia. Three developed transient ECG changes and one herpes zoster. There were four device-related infections, two requiring hospitalization (one required surgical drainage of an abscess). All lesions re-epithelialized. A total of 250 bed-days were saved over a 67-day period. These results indicate that in selected patients, out-patient therapy for cutaneous leishmaniasis with parenteral high-dose sodium stibogluconate may be appropriate, provided there is adequate monitoring of therapy.
Adult↗
Anesthesia for intranasal surgery: a comparison between tracheal intubation and the flexible reinforced laryngeal mask airway.
UNLABELLED: The purpose of the study was to assess the suitability and safety of the flexible reinforced laryngeal mask airway (FRLMA) for intranasal surgery (INS) anesthesia. A secondary objective was to compare the incidence of complications of removal of the FRLMA with tracheal extubation in awake and anesthetized patients. One hundred fourteen ASA physical status I and II patients requiring INS were randomly assigned into three groups: Group I = FRLMA, Group II = endotracheal tube (ET) extubated awake, and Group II = ET extubated deeply anesthetized. In Group I, the incidence of coughing and oxyhemoglobin desaturation at removal was significantly reduced compared with that in Groups II and III (P < 0.05). There were no episodes of postremoval laryngospasm in Group I; in Group III, the incidence was 19% (P < 0.05), whereas in Group II, it was 6% (not significantly different). The number of patients with oxyhemoglobin desaturation < or = 92% on admission to the postanesthesia care unit was 0% in Group I, 26% in Group II (P < 0.05), and 16% in Group III (not significantly different). At bronchoscopy, the incidence of blood visible in the airway was low and similar among the three groups (3%, 6%, and 3%, respectively). There were no significant differences in the incidence of airway complications between Groups II and III. IMPLICATIONS: We compared airway management for intranasal surgery anesthesia using a new device, the flexible reinforced laryngeal mask airway, with the current standard of tracheal intubation. The study demonstrates that the flexible reinforced laryngeal mask airway can provide a safe, protected airway with a smoother emergence from anesthesia than tracheal intubation.
Adult↗
Becoming aware: knowing yourself to care for others.
This article describes the four quadrants of a whole person as a model of balanced health, then focuses on the natural emotions that volunteers and professionals encounter in hospice work. The significance of self-awareness in emotional and spiritual realms is emphasized to assist hospice workers in providing high-quality care and in nurturing themselves for the long term.
Adaptation, Psychological↗
Spider bites: assessment and management.
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Diagnosis, Differential↗
A comparison of two dosing regimens of succimer in children with chronic lead poisoning.
There is limited information defining the optimal dosing regimen of succimer in the treatment of children with chronic lead poisoning. It is typically administered as a five day course of high dose therapy (1,050 mg/m2/day) followed by 14 days of low dose therapy (700 mg/m2/day). This study compared the effect on blood lead concentrations (BPb) of treatment with this standard regimen and an alternate regimen consisting of two courses of high dose therapy separated by one week. There were significant reductions in the mean BPb in both the standard (n = 7) and alternate (n = 4) treatment groups but there was not a significant difference between the groups. In the standard group, the BPb decreased from 33 +/- 4 to 27 +/- 6 mcg/dL. The BPb decreased from 33 +/- 6 to 23 +/- 4 mcg/dL in those treated with alternate therapy. This study suggests that two short courses of high dose therapy may be an acceptable alternative to standard succimer therapy. Because of the small size of this study, other studies are warranted.
Chelating Agents↗
The economic burden of schizophrenia in Canada.
OBJECTIVE: To estimate the financial burden of schizophrenia in Canada in 1996. METHOD: Using a prevalence-based approach, all direct health care costs, administrative costs of income assistance plans, and costs of incarceration attributable to schizophrenia were determined. Also included was the value of lost productivity associated with premature mortality and morbidity. In addition to using published papers and documents, direct contact was made with representatives from various provincial and federal programs for estimates of the direct health care and non-health care costs. RESULTS: The estimated number of persons with schizophrenia in Canada in 1996 was 221,000, with equal distribution between males and females. The direct health care and non-health care cost was estimated to be $1.12 billion in 1996. In addition, another $1.23 billion in lost productivity associated with morbidity and premature mortality was attributable to schizophrenia. CONCLUSIONS: The total financial burden of schizophrenia in Canada was estimated to be $2.35 billion in 1996. The largest category of cost was morbidity (52%), followed by acute care and psychiatric hospital admissions (14% and 10% respectively). Given the magnitude of these cost estimates, there are large potential cost savings with more effective management and control of this debilitating disease.
Adolescent↗
Economic evaluation of long-term management strategies for erosive oesophagitis.
OBJECTIVE: To compare the expected costs and outcomes of alternative strategies for the management of patients with erosive oesophagitis. DESIGN: There were 3 components to the overall analytic approach. First, a decision model was constructed to compare expected costs and outcomes of 6 management strategies. Second, principles of quantitative literature review and meta-analysis were used to determine probabilities of clinical events (i.e. oesophagitis healing and recurrence). Finally, principles of cost-effectiveness analysis were used to compare treatment alternatives in terms of dominance and incremental cost effectiveness. The viewpoint for the study was that of a provincial government payer for healthcare over a 1-year period. MAIN OUTCOME MEASURES AND RESULTS: Healing rates were significantly higher for proton pump inhibitors (PPI) [p < 0.001]. Recurrence rates were significantly higher for intermittent therapy (placebo) and lower for regular dose PPI (p < 0.001). Maintenance prokinetic agent (PA) is dominated (i.e. more costly and less effective) and step-down maintenance PPI is dominated through principles of extended dominance. The 'efficient frontier' is represented by: maintenance H2-receptor antagonist (H2RA), intermittent PPI, step-down maintenance H2RA and maintenance PPI. CONCLUSIONS: The price of H2RA is a key factor influencing whether step-down maintenance PPI forms part of, or is contained within, the 'efficient frontier' of long term management for erosive oesophagitis.
Costs and Cost Analysis↗
Elevation of serum riboflavin carrier protein in breast cancer.
Presently available tumor markers have had a limited clinical impact. Riboflavin carrier protein (RCP) is an estrogen inducible protein that occupies a key position in riboflavin metabolism. Because other vitamin carrier proteins (VCP) have been shown to be overexpressed in patients with malignant disease, we evaluated serum RCP levels in patients with adenocarcinoma of the breast. In this prospective blinded study, patients with breast cancer, benign breast disease, and healthy controls were analyzed for RCP levels. Using a highly sensitive RIA, we observed that serum RCP levels were significantly elevated in women with breast cancer (n = 52) as compared with control subjects [n = 50; 6.06 +/- 7.27 ng/ml versus 0.70 +/- 0.19 ng/ml (mean +/- SD), respectively; P < 0.0001]. A serum RCP level of > or = 1.0 ng/ml was highly predictive of the presence of breast cancer, detecting 88% of tumors in stages I-II and 100% of tumors in stages III-IV. Overall, this RCP assay has a sensitivity of 92.3%, a specificity of 88%, a positive predictive value of 88.9%, and a negative predictive value of 91.7%. These results show increased serum levels of RCP in breast adenocarcinoma patients and suggest that RCP levels may be useful as a new marker for breast cancer. The positive predictive value in early-stage breast cancer suggests that the RCP assay may be a useful adjunct to present screening technology.
Adenocarcinoma↗
Measuring dreaming as a beyond waking experience in Rogers's conceptual model.
This article describes the development of an instrument, the Assessment of Dream Experience. This instrument was developed within the context of Rogers's conceptual model, the science of unitary human beings, and was designed to measure dreaming as a beyond waking experience. A detailed description of the instrument and its psychometric properties is presented. Recommendations for future use are provided.
Adult↗
Disease progression in a cohort of infants with vertically acquired HIV infection observed from birth: the Women and Infants Transmission Study (WITS).
BACKGROUND: The Women and Infants Transmission Study is an ongoing prospective cohort study of HIV-infected pregnant women and their infants. We used the 1994 U.S. Centers for Disease Control and Prevention (CDC) classification system for HIV infection in children to describe HIV disease progression in 128 HIV-infected children, and examined maternal and infant characteristics associated with disease course. METHODS: The Kaplan-Meier method was used to calculate probabilities of entry into CDC clinical classes A, B, and C (mild, moderate, and severe HIV disease); CDC immunologic stages 2 and 3; and death. Relative risks of progression for selected predictor events were estimated using the Cox proportional hazards model. RESULTS: With a median 24 months of follow-up, the median ages at entry into clinical classes A, B and C were 5, 11, and 48 months, respectively. Increased risk of progression to class C was seen in infants who had: onset of class B events (p < .001); progression to immunologic stage 2 (p < .001) or 3 (p < .001); early culture positivity (in first 48 hours, p < .01; in first 7 days, p = .03); and early appearance (within the first 3 months of life) of lymphadenopathy, hepatomegaly, or splenomegaly (p < .001). CONCLUSIONS: Reaching specific clinical or immunologic stages were strong predictors of progression to AIDS or death. Early onset of clinical signs (onset of lymphadenopathy, hepatomegaly, or splenomegaly < or =3 months of age), and early culture positivity (within the first 48 hours or within the first week of life), defined the infant with highest risk of disease progression.
Cohort Studies↗
An outbreak of multi-drug-resistant tuberculosis in a London teaching hospital.
We describe the epidemiology and control of a hospital outbreak of multi-drug-resistant tuberculosis (MDR-TB). A human immunodeficiency virus (HIV)-negative patient with drug-sensitive tuberculosis developed MDR-TB during a period of unsupervised therapy. She was admitted to an isolation room in a ward with HIV-positive patients, but the room, unbeknown to hospital staff, was at positive-pressure relative to the main ward. Seven HIV-positive contacts developed MDR-TB. The diagnosis in the second patient was delayed, partly because acid-fast bacilli in his sputum were assumed to be Mycobacterium avium-intracellulare. All the available Mycobacterium tuberculosis isolates were indistinguishable by molecular typing. Nearly 1400 staff and patient contacts were offered screening, but the screening programme detected only one of the cases. Despite therapy, the index patient and two of the contacts died. HIV-positive patients are more likely than others to develop tuberculosis after exposure, and the disease may progress more rapidly. In these patients the possibility that acid-fast bacilli may represent M. tuberculosis must always be considered. Patients with tuberculosis (suspected or proven) should not be nursed in the same wards as immunosuppressed patients, and should be isolated. MDR-TB cases must be isolated in negative-pressure rooms. Hospital side-rooms may be positive-pressure as a fire safety measure; infection control teams must be aware of the airflows in all isolation rooms, and must be consulted during the design of hospital buildings. Good communication between infection control teams and clinicians is important, and all medical and nursing staff must be aware of the principles of management of patients with proven or suspected tuberculosis and MDR-TB.
AIDS-Related Opportunistic Infections↗
SB-224289--a novel selective (human) 5-HT1B receptor antagonist with negative intrinsic activity.
1. Human 5-HT1B (h5-HT1B) and human 5-HT1D (h5-HT1D) receptors show remarkably similar pharmacology with few compounds discriminating the receptors. We report here on a novel compound, SB-224289 (1'-Methyl-5-[[2'-methyl-4'-(5-methyl- 1,2,4-oxadiazol-3-yl)biphenyl-4-yl]carbonyl]-2,3,6,7-tetrahydro spiro [furo [2,3-f]indole-3,4'-piperidine] oxalate), which has high affinity for h5-HT1B receptors (pK1=8.16+/-0.06) and displays over 75 fold selectivity for the h5-HT1B receptor over all other 5-HT receptors including the h5-HT1D receptor and all other receptors tested thus far. 2. Functional activity of SB-224289 was measured in a [15S]GTPgammaS binding assay on recombinant h5-HT1B and h5-HT1D receptors expressed in Chinese Hamster Ovary (CHO) cells. SB-224289 displayed negative intrinsic activity at both receptors with higher potency at h5-HT1B receptors. SB-224289 caused a rightward shift of agonist concentration response curves consistent with competitive antagonism and generated affinities comparable with those obtained from competition radioligand receptor binding studies. 3. SB-224289 potentiated [3H]5-HT release from electrically stimulated guinea-pig cerebral cortical slices to the same extent as as the non-selective 5-HT1 antagonist methiothepin. SB-224289 also fully reversed the inhibitory effect of exogenously superfused 5-HT on electrically stimulated release. 4. Using SB-224289 as a tool compound, we confirm that in guinea-pig cerebral cortex the terminal 5-HT autoreceptor is of the 5-HT1B subtype.
Animals↗