[More physicians should be engaged in standardization procedures].
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Communication↗
Biomedical subjects
K Johnson
Publications and source records attributed to K Johnson.
[Copenhagen may have the solution of problems in Stockholm].
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Centralized Hospital Services↗
[A new prescription form introduced to prevent falsifications].
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Benzodiazepines↗
Strategy and planning for chemopreventive drug development: clinical development plans II.
This is the second publication of Clinical Development Plans from the National Cancer Institute, Division of Cancer Prevention and Control, Chemoprevention Branch and Agent Development Committee. The Clinical Development Plans summarize the status of promising chemopreventive agents regarding evidence for safety and chemopreventive efficacy in preclinical and clinical studies. They also contain the strategy for further development of these drugs, addressing pharmacodynamics, drug effect measurements, intermediate biomarkers for monitoring efficacy, toxicity, supply and formulation, regulatory approval, and proposed clinical trials. Sixteen new Clinical Development Plans are presented here: curcumin, dehydroepiandrosterone, folic acid, genistein, indole-3-carbinol, perillyl alcohol, phenethyl isothiocyanate, 9-cis-retinoic acid, 13-cis-retinoic acid, l-selenomethionine and 1, 4-phenylenebis(methylene)selenocyanate, sulindac sulfone, tea, ursodiol, vitamin A, and (+)-vorozole. The objective of publishing these plans is to stimulate interest and thinking among the scientific community on the prospects for developing these and future generations of chemopreventive drugs.
Animals↗
Association of CTG repeats and the 1-kb Alu insertion/deletion polymorphism at the myotonin protein kinase gene in the Japanese population suggests a common Eurasian origin of the myotonic dystrophy mutation.
We have studied linkage disequilibrium between CTG repeats and an Alu insertion/deletion polymorphism at the myotonin protein kinase gene (DMPK) in 102 Japanese families, of which 93 were affected with myotonic dystrophy (DM). All of the affected chromosomes are in complete linkage disequilibrium with the Alu insertion allele. Among the normal chromosomes, alleles of CTG repeats 5 and > or = 17 are exclusively associated with the insertion allele. On the other hand, intermediate alleles of 11-16 repeats show a significantly greater association with the deletion allele. A strikingly similar pattern of linkage disequilibrium observed in European populations suggests a common origin of the DM mutation in the Japanese and European populations.
Asian People↗
Second primary cancers after vulvar and vaginal cancers.
OBJECTIVE: Our objective was to examine the occurrence of second primary cancers after vaginal and vulvar cancers. STUDY DESIGN: Women in whom cancers of the vagina (in situ, n=461; invasive, n=888) and vulva (in situ, n=2898; invasive, n=2685) were diagnosed between 1973 and 1988 were identified from nine population-based cancer registries. Subjects were followed through 1989 for the development of a subsequent primary cancer. RESULTS: We found increased risks of all second cancers combined among women with cancer of the vulva (observed/expected in situ = 1.5; observed/expected invasive = 1.3) and vagina observed/expected invasive = 1.2). Most of the excess second cancers were smoking related (e.g., cancers of the lung, buccal cavity and pharynx, esophagus, nasal cavity and larynx) or related to infection with human papillomavirus (e.g., cervix, vulva, vagina, and anus). CONCLUSION: These associations indicate that the follow-up care of women with cancers of the vulva and vagina should involve efforts to promote smoking cessation. The data are also consistent with a common sexually related cause for cancers of the cervix, vulva, vagina, and anus.
Cohort Studies↗
L-arginine administration during reperfusion improves pulmonary function.
BACKGROUND: Nitric oxide is crucial to the maintenance of vascular homeostasis. Because nitric oxide levels decline upon lung reperfusion, infusion of L-arginine, a nitric oxide precursor, during reperfusion might prove effective at ameliorating reperfusion injury. METHODS: Neonatal piglet heart-lung blocks were preserved with Euro-Collins solution for 12 hours, rewarmed at room temperature for 1 hour, and reperfused for 10 minutes with either whole blood (n = 5), whole blood containing L-arginine (10 mmol/L; n = 6), or leukocyte-depleted blood (n = 6) on an isolated, blood-perfused, working heart-lung circuit. After the initial 10 minutes, all blocks received whole blood for 4 hours. Control blocks were continuously perfused on the circuit without intervening ischemia (n = 6). RESULTS: The partial pressure of oxygen in the whole blood group (113.8 +/- 33.1 mm Hg) was significantly less than in controls (417.3 +/- 6.2 mm Hg; p < 0.01). Lung compliance was significantly less in the whole blood group (0.8 +/- 0.2 mL/cm H2O) than in controls (2.9 +/- 0.4 mL/cm H2O; p < 0.01). The L-arginine and leukocyte-depleted blood groups showed no significant difference from controls. CONCLUSIONS: L-Arginine infusion during reperfusion improves pulmonary function, making it a simple alternative to leukocyte depletion.
Animals↗
Case report: asbestos related pericardial disease.
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Asbestos↗
Structural characterization of 15-hydroxytrichodiene, a sesquiterpenoid produced by transformed tobacco cell suspension cultures expressing a trichodiene synthase gene from Fusarium sporotrichioides.
Tobacco (Nicotiana tabaccum) cell suspension cultures transformed with a gene encoding trichodiene synthase, a sesquiterpene synthase from the fungus Fusarium sporotrichioides, produced a novel sesquiterpenoid derived from the in vivo production of trichodiene. Mass and nuclear magnetic resonance spectroscopic analyses identified the new compound as 15-hydroxytrichodiene. The in vivo hydroxylation of trichodiene by transformant tobacco cell suspension cultures demonstrates that the introduction of a foreign sesquiterpene synthase gene can result in the production of novel sesquiterpenoid metabolites.
Carbon-Carbon Lyases↗
Long-term low-dose cyclosporine therapy for severe psoriasis: effects on renal function and structure.
BACKGROUND: The effectiveness of cyclosporine in the treatment of severe psoriasis is well known. OBJECTIVE: We evaluated the efficacy and toxicity of systemic cyclosporine in patients with severe psoriasis, observing short-term (12 weeks) and long-term (3 to 5 years) effects. METHODS: To further elucidate efficacy and safety, 42 patients with severe psoriasis were treated initially with cyclosporine 5 to 6 mg/kg per day for 12 weeks. A subset of 14 patients continued maintenance treatment for 3.5 years to study the long-term effects of cyclosporine on renal function and structure. Renal biopsies were performed after 2.5 years and 3.5 years of treatment. Renal histologic findings were correlated with renal function. RESULTS: By weeks 8 and 12, 64% (n = 27) and 86% (n = 36) of patients, respectively, were rated clear or almost clear of the psoriasis. However, a subpopulation of 15 patients did not respond to 5 mg/kg daily but improved when the dose was increased to 6 mg/kg daily. Clearance or near clearance was achieved in 67% of this subpopulation after 4 weeks. For the 29 patients whose glomerular filtration rate (GFR) was measured, mean GFR fell by 7% from baseline to week 4 (p < 0.05). This change was reversible when dosage was reduced by 1 mg/kg per day in each of these patients. Patients older than 45 years of age experienced significant elevation of mean diastolic blood pressure and had reduced GFR and increased serum creatinine. After 2.5 years, of the 14 patients who continued maintenance treatment, two had biopsy specimens that showed moderate interstitial fibrosis and tubular atrophy. The remainder showed only minimal to mild structural damage. After 3.5 years of cyclosporine treatment, repeat renal biopsy specimens revealed slight increases in structural changes in nine subjects. These changes correlated with increasing age and drug-induced hypertension. CONCLUSION: We conclude that 5 mg/kg of cyclosporine daily is usually an effective initial dose for psoriasis. Patients who do not respond will often benefit from elevation of the dose to 6 mg/kg daily. Older patients experience cyclosporine-induced hypertension and changes in renal function and structure more frequently than do younger patients.
Adult↗
Inhibition of macrophage nitric oxide production by tetrahydrocannabinol in vivo and in vitro.
delta 9-Tetrahydrocannabinol (THC, 10 micrograms) was administered intraperitoneally to thioglycollate-treated mice. After 18 h, peritoneal macrophages were harvested and nitric oxide (NO.) production was induced by lipopolysaccharide (LPS, 1 microgram/ml) and interferon-gamma (IFN-gamma, 0.1-10 U/ml). Macrophages from THC-treated mice produced about half as much NO. as controls. THC (1 microgram/ml) added in vitro caused further inhibition. Greater inhibition was observed at the lower (0.1-0.3 U/ml) IFN-gamma concentrations. The results suggest that the use of THC can reduce NO. production and thereby affect host defense mechanisms, inflammation and autoimmune responses.
Animals↗
Age as a risk factor for inadequate emergency department analgesia.
Inadequate treatment of pain, which has been termed as "oligoanalgesia", appears to be common in a number of practice settings, including the emergency department (ED). The purpose of this study was to determine whether elderly patients with isolated long-bone fractures are less likely to receive analgesics in the ED than a similar cohort of younger patients. Consecutive adult patients (aged 20 to 50 years or older than 70 years) presenting to the ED with isolated long-bone fractures were evaluated using a retrospective cohort study design. Patient demographics, ED treatment, and disposition were analyzed (t tests, chi2) to identify significant differences between the two age groups. Analgesic use was recorded as oral or parenteral, nonnarcotic or narcotic, and low or high dose (less than or at least the equivalent of 10 mg parenteral morphine sulfate, respectively). A total of 231 patients met the inclusion criteria, of whom 109 were elderly (mean age, 80.6 +/- 7.4 years) and 122 nonelderly (mean age 33.9 +/- 8.0 years). Nonelderly patients were more likely than the elderly to receive ED pain medication (80% vs 66%, P =.02) within a shorter period of time (mean 52 min vs 74 min, P = .02), and at a higher equivalent dose (44% vs 19%, P = .002). Younger patients also tended to receive more narcotic medications (98% vs 89%, P = .03). Inadequate use of analgesics in adult ED patients with acute fractures appears to be common. A chronologic basis for variability in analgesic practice needs to be further characterized.
Adult↗
Cadherin function is required for axon outgrowth in retinal ganglion cells in vivo.
The cell-cell adhesion molecule N-cadherin strongly promotes neurite outgrowth in cultured retinal neurons. To test whether cadherins regulate process outgrowth in retinal neurons in vivo, we have blocked cadherin function in single cells by expression of a dominant negative N-cadherin mutant. We report that when cadherin function is inhibited, axon and dendrite outgrowth are severely impaired, particularly in retinal ganglion cells. Laminar migration and cell type specification, by contrast, appear unaffected. Further, expression of the catenin-binding domain of N-cadherin, which blocks cadherin-mediated adhesion in early embryos, does not affect axon outgrowth, suggesting that outgrowth and adhesion are mediated by distinct regions of the cytoplasmic domain. These findings indicate that cadherins play an essential role in the initiation and extension of axons from retinal ganglion cells in vivo.
Animals↗
Microsatellite instability in early sporadic breast cancer.
We have studied the incidence of microsatellite instability at three trinucleotide repeats and seven dinucleotide repeats from five chromosomal regions, in a group of 30 mammographically detected 'early' invasive breast cancers and correlated its occurrence with clinicopathological parameters. The myotonic dystrophy (DM-1) trinucleotide repeat was analysed in 48 additional cases. In 4 out of 78 (5%) paired tumour-normal DNA samples we found evidence of somatic microsatellite instability at DM-1: a novel allele of a different size was seen in the tumour DNA which was not present in the normal DNA sample. All four tumours that showed evidence of instability were from the core group of 30 cases (13%) and were well or moderately differentiated, oestrogen receptor-positive, infiltrating ductal carcinomas. Two of these tumours were unstable at nine of ten loci studied, both trinucleotide and dinucleotide repeats. DNA prepared from different normal tissues showed no evidence of instability, for all four instability cases. These data indicate that microsatellite instability is specific to the tumour DNA and is an early event in the genesis of some sporadic breast cancers.
Breast Neoplasms↗
Narrative development in late talkers: early school age.
Children with slow expressive language development (SELD) as toddlers and a control group of children with normal language development (NL) were followed to early school age. Children with SELD were, at that point, subdivided into two groups: those who had moved within the normal range of expressive language (the History of Expressive Language Delay [HELD] subgroup); and those who continued to score below the normal range in expressive language at school age (the Expressive Language Delay [ELD] subgroup). During their kindergarten, first, and second grade years, they were administered a narrative generation task. Narratives were analyzed for MLU, lexical diversity, amount of information included, proportion of complete cohesive ties, and overall stage of narrative maturity. In kindergarten, children with normal language history scored significantly higher than those with HELD and ELD on lexical diversity and narrative stage; and higher than those with ELD in proportion of complete cohesive ties. In first grade, children with normal language history again scored significantly higher than those with HELD and ELD on narrative maturity, with no other significant differences. In second grade, there were no significant differences among the groups.
Age Factors↗
AS-1 red cells for neonatal transfusions: a randomized trial assessing donor exposure and safety.
BACKGROUND: Despite recent optimism about the use of erythropoietin therapy to treat the anemia of prematurity, very-low-birth-weight infants who are severely ill receive multiple red cell (RBC) transfusions. Many physicians transfuse relatively fresh RBCs to newborn infants, exposing them to multiple donors and possibly increasing their risk of acquiring transfusion-transmitted infections. STUDY DESIGN AND METHODS: A randomized, single-blind clinical trial was conducted to determine, as the primary endpoint, whether RBCs collected from one dedicated donor and stored for < or = 42 days in AS-1 storage media could safely supply all small-volume RBC transfusions (15 mL/kg/dose) needed by very-low-birth-weight infants (0.6-1.3 kg) during the first 84 days of life. Secondary endpoints were the assessment of the possible adverse clinical and biochemical effects of transfusing AS-1 RBCs stored for < or = 42 days. Control infants received identical nursery care, except they received fresh RBCs stored < or = 7 days in CPDA-1. RESULTS: Infants transfused with AS-1 RBCs were exposed to a mean of 1.6 donors,-compared with an exposure to 3.7 donors for infants given CPDA-1 RBCs (p < 0.05). Neither clinical transfusion reactions nor the results of multiple laboratory tests were significantly different in infants who received slow transfusions (15 mL/kg) of AS-1 RBCs stored for < or = 42 days and in infants who received the same volume of CPDA-1 RBCs stored < or = 7 days. CONCLUSION: AS-1 RBCs, usually from only one dedicated donor, can safely supply all RBCs needed by most very-low-birth-weight infants-a practice that decreases donor exposure and likely increases transfusion safety.
Adenine↗
Road to awareness: an individualized training package for increasing knowledge and comprehension of personal deficits in persons with acquired brain injury.
Research suggests that awareness of one's deficits may be a significant factor in the recovery process after acquired brain injuries (ABI). Various methods have been employed to teach awareness of the potential sequelae of ABI. The present study extended the use of a board game format to teach awareness to adults with ABI who exhibited serious unwanted behaviours. It used an individualized training package in conjunction with a game format in order to more specifically target individual client awareness of personal deficits in two areas: cognition and behaviour. Training focused on the first three levels within Bloom's Cognitive Taxonomy: knowledge, comprehension, and application. Components of both the multiple-baseline and multiple-probe design were used to demonstrate experimental control. All three participants responded favourably to training, as evidenced by increases in percentage of questions answered correctly during the game sessions and in pre/post-generalization probes in both cognitive and behavioural categories.
Adult↗
Myotonic dystrophy: will the real gene please step forward!
The mutation underlying myotonic dystrophy (DM) was identified at the end of 1991 amidst great rejoicing from the patients supporting the research and, not least, from those who spent so long searching for it. Subsequently, the molecular genetic phenomena associated with DM have been clearly explained by the transmission behaviour of the expanding repeat, which remains the only mutation that has been described in patients. We understand the molecular basis of anticipation, why the severe congenital form is almost exclusively transmitted by affected mothers and we have widely accepted models of the population genetics of DM. Yet, despite all these clearly explained molecular events, we appear to be hardly any closer to understanding the molecular pathology of DM than when the mutation was first identified. To understand the reason for this, we have to look in detail at the mutation itself, and in particular at the locus and its complex nuances. In doing so, we begin to realise that DM is unique amongst the Mendelianly inherited disorders, in that the mutation, because of its location in a very gene-rich region of the genome, probably simultaneously renders several genes dysfunctional. The somatic heterogeneity of the repeat, coupled with the involvement of several genes, accounts for the pleiotropy observed in the phenotype. Added to this complexity is the uncertainty of the level at which gene dysfunction or gain of function is occurring. It is possibly at the level of DNA/chromatin structure and/or RNA regulation/processing, and all of these pathways may, in different tissues, contribute to the final phenotype.
Animals↗