The Chicago Tribune series on nursing mistakes.
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Clinical Competence↗
Biomedical subjects
A Green
Publications and source records attributed to A Green.
Time for change ... relationships between nursing and medicine.
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Agonistic Behavior↗
Hormone therapy use in Australian-born women: a longitudinal study.
OBJECTIVES: To describe the pattern of use of hormone therapy (HT) among Australian women, and its side-effects and benefits, and to compare baseline characteristics of HT users with never users. DESIGN: Longitudinal community-based study with annual interviews. SETTING: Melbourne, May 1991-October 1997. PARTICIPANTS: 357 Australian-born women aged 45-55 years who were pre- or perimenopausal and not using HT at baseline. MAIN OUTCOME MEASURES: Rates of HT use; baseline characteristics of users and non-users; side effects and benefits of HT use. RESULTS: 151 women (42%) used HT over the six years and 93 (26%) were current users at six-year follow-up. HT users did not differ significantly from non-users in lifestyle, sociodemographic and cardiovascular risk factors or in most health status factors at baseline. However, HT users were significantly more likely to have had a breast examination by a health professional (odds ratio [OR], 2.60; 95% CI, 1.62-4.17), to have had a tubal ligation (OR, 1.73; 95% CI, 1.09-2.74), to report a history of premenstrual complaints (OR, 1.72; 95% CI, 1.08-2.74), to agree that women "regret when their period stops for the last time" (OR, 1.69; 95% CI, 1.04-2.74), and to report that they took non-prescription medications (OR, 1.62; 95% CI, 1.02-2.59). Most (84%) HT users described benefits (most commonly relief of hot flushes and improved wellbeing), while 53% complained of side effects (most commonly weight gain and breast tenderness). CONCLUSIONS: HT users did not differ significantly from non-users at baseline in most characteristics. Long-term follow-up of this cohort is now required to assess any difference in cardiovascular events or other health outcomes between HT users and non-users.
Australia↗
Children with acute lymphoblastic leukemia who receive T-cell-depleted HLA mismatched marrow allografts from unrelated donors have an increased incidence of primary graft failure but a similar overall transplant outcome.
Disparity for HLA in unrelated donor bone marrow transplantation (BMT) increases the risk of graft rejection and graft-versus-host disease (GVHD) and may compromise transplant outcome. We have compared the outcome of matched and mismatched transplants from unrelated donors in 137 children with acute lymphoblastic leukemia (ALL). Their disease status was complete remission (CR)-1, 24 patients; CR-2, 88 patients; CR-3, 18 patients; CR-4, 2 patients; and relapse, 5 patients. CAMPATH monoclonal antibodies were used for T-cell depletion and cyclosporin A was given to 134 children together with short-course methotrexate in 43, mainly when there was HLA disparity. Fifty-two donor/recipient pairs were HLA-mismatched, 41 at HLA-A and -B and 11 at HLA-DR and -DQ loci. Overall graft failure was increased in recipients of marrow mismatched at either HLA-A, -B, -DR, or -DQ (15.7% v 4.8%; P =.057) mainly because there was a higher proportion of children with primary graft failure (11. 8% v 1.2%; P =.012). The presence of an HLA-C locus mismatch did not independently increase the likelihood of graft failure. There was no significant difference in the incidence of acute GVHD >/= grade 2 between the matched and mismatched groups (P =.849). For patients in CR-2, the risk of relapse post-BMT was significantly lower if leukemic relapse occurred off-treatment (P =.005). The Kaplan-Meier overall and leukemia-free survival (LFS) estimates for recipients of matched and mismatched BMT, respectively, at 36 months were 49% versus 42% (P =.380) and 45% versus 40% (P =.654). Although HLA mismatching results in an increased occurrence of primary graft failure with T-cell-depleted allografts, it allows more donors to be identified rapidly for children with ALL without compromising overall transplant outcome.
Adolescent↗
The pathogenesis of melanoma induced by ultraviolet radiation.
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Environmental Exposure↗
Daily sunscreen application and betacarotene supplementation in prevention of basal-cell and squamous-cell carcinomas of the skin: a randomised controlled trial.
BACKGROUND: The use of sunscreens on the skin can prevent sunburn but whether long-term use can prevent skin cancer is not known. Also, there is evidence that oral betacarotene supplementation lowers skin-cancer rates in animals, but there is limited evidence of its effect in human beings. METHODS: In a community-based randomised trial with a 2 by 2 factorial design, individuals were assigned to four treatment groups: daily application of a sun protection factor 15-plus sunscreen to the head, neck, arms, and hands, and betacarotene supplementation (30 mg per day); sunscreen plus placebo tablets; betacarotene only; or placebo only. Participants were 1621 residents of Nambour in southeast Queensland, Australia. The endpoints after 4.5 years of follow-up were the incidence of basal-cell and squamous-cell carcinomas both in terms of people treated for newly diagnosed disease and in terms of the numbers of tumours that occurred. Analysis of the effect of sunscreen was based only on skin cancers that developed on sites of daily application. All analyses were by intention to treat. FINDINGS: 1383 participants underwent full skin examination by a dermatologist in the follow-up period. 250 of them developed 758 new skin cancers during the follow-up period. There were no significant differences in the incidence of first new skin cancers between groups randomly assigned daily sunscreen and no daily sunscreen (basal-cell carcinoma 2588 vs 2509 per 100,000; rate ratio 1.03 [95% CI 0.73-1.46]; squamous-cell carcinoma 876 vs 996 per 100,000; rate ratio 0.88 [0.50-1.56]). Similarly, there was no significant difference between the betacarotene and placebo groups in incidence of either cancer (basal-cell carcinoma 3954 vs 3806 per 100,000; 1.04 [0.73-1.27]; squamous-cell carcinoma 1508 vs 1146 per 100,000; 1.35 [0.84-2.19]). In terms of the number of tumours, there was no effect on incidence of basal-cell carcinoma by sunscreen use or by betacarotene but the incidence of squamous-cell carcinoma was significantly lower in the sunscreen group than in the no daily sunscreen group (1115 vs 1832 per 100,000; 0.61 [0.46-0.81]). INTERPRETATION: There was no harmful effect of daily use of sunscreen in this medium-term study. Cutaneous squamous-cell carcinoma, but not basal-cell carcinoma seems to be amenable to prevention through the routine use of sunscreen by adults for 4.5 years. There was no beneficial or harmful effect on the rates of either type of skin cancer, as a result of betacarotene supplementation.
Adult↗
Nitric oxide protects PC12 cells from serum deprivation-induced apoptosis by cGMP-dependent inhibition of caspase signaling.
Although nitric oxide (NO) induces neuronal cell death under some conditions, it also can prevent apoptosis resulting from growth factor withdrawal. We investigated the molecular mechanism by which NO protects undifferentiated and differentiated PC12 cells from trophic factor deprivation-induced apoptosis. PC12 cells underwent apoptotic death in association with increased caspase-3-like activity, DNA fragmentation, poly(ADP-ribose) polymerase (PARP) cleavage, and cytochrome c release after 24 hr of serum withdrawal. The apoptosis of PC12 cells was inhibited by the addition of NO-generating donor S-nitroso-N-acetylpenicillamine (SNAP) (5-100 microM) and the specific caspase-3-like protease inhibitor Ac-Asp-Glu-Val-Asp-aldehyde (Ac-DEVD-cho) but not the YVADase (or caspase-1-like protease) inhibitor N-acetyl-Tyr-Val-Ala-Asp-aldehyde (Ac-YVAD-cho). SNAP and Ac-DEVD-cho prevented the increase in DEVDase (caspase-3-like protease) activity. The SNAP-mediated suppression of DEVDase activity was only minimally reversed by the incubation of cell lysate with dithiothreitol, indicating that NO did not S-nitrosylate caspase-3-like proteases in PC12 cells. Western blot analysis showed that NO inhibited the proteolytic activation of caspase-3. The cGMP analog 8-bromo-cGMP (8-Br-cGMP) blocked apoptotic cell death, caspase-3 activity and activation, and cytochrome c release. The soluble guanylyl cyclase inhibitor 1-H-oxodiazol-[1,2,4]-[4,3-a] quinoxaline-1-one (CODQ) significantly attenuated NO-mediated, but not 8-Br-cGMP-dependent, inhibition of apoptotic cell death, PARP cleavage, cytochrome c release, and DEVDase activity. Furthermore, the protein kinase G inhibitor KT5823 reversed both SNAP- and 8-Br-cGMP-mediated anti-apoptotic events. All these apoptotic phenomena were also suppressed by NO production through neuronal NO synthase gene transfer into PC12 cells. Furthermore, similar findings were observed in differentiated PC12 cells stimulated to undergo apoptosis by NO donors and NGF deprivation. These findings indicate that NO protects against PC12 cell death by inhibiting the activation of caspase proteases through cGMP production and activation of protein kinase G.
Animals↗
[Systemic lupus erythematosus in the county of Fynen. An epidemiologic study].
The incidence and prevalence of systemic lupus erythematosus (SLE) has never been investigated in Denmark, whereas international studies have reached divergent results. In the study patients were ascertained from diagnosis-based registers of inpatients and outpatients, notifications from physicians, and an autoimmune register. Diagnoses were validated and patients classified according to the American College of Rheumatology criteria: definite SLE (D-SLE) > or = 4 and incomplete SLE (I-SLE) < 4 criteria. The point prevalence as of Jan. 1, 1995, was 21.7/100,000 (CI 95% 17.3-26.8) for D-SLE and 5.2/ 100,000 (CI 95% 3.2-8.0) for I-SLE. The mean annual incidence in 1990-94 was 2.5/100,000 (CI 95% 1.8-3.3). Figures for annual incidence and prevalence were in accordance with recent British reports but considerably lower than Swedish and Icelandic results. Although methodological issues should be considered, the results point to a different distribution of SLE in otherwise closely related nationalities.
Adult↗
Rationing of sildenafil. True debate is needed.
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Attitude to Health↗
[Incidence of type 1 childhood diabetes in Hungary (1978-1997). Hungarian Committee on the Epidemiology of Childhood Diabetes].
The incidence of Type 1 diabetes in 2417 children aged 0-14 years was studied between 1978 and 1997. Statistical analysis of the data in the twenty-year period showed a steady increase in incidence of Type 1 diabetes with an average rate of 4.8% (95% CI 4.0-5.5) per annum. The incidence rate was lowest in children aged 0 to 4 years and the highest in the age group 10 to 14 years. This increase in incidence was similar for all age groups, but it was most pronounced in the 10 to 14 year-old age group. One hundred and twenty one of the 1239 families (9.7%), one of parents was also reported to have Type 1 diabetes and in 3 (0.2%) families both parents had Type 1 diabetes. Twenty two (2.3%) of the diabetic families had a sibling with Type 1 diabetes. The nearly three-fold increase in incidence during the last two decades (3.8 per 100,000 per year in 1978; 10.7 per 100,000 per year) was probably due to environmental factors, while the high degree of familial clustering emphasises the role of genetic factors in the etiology of Type 1 diabetes.
Adolescent↗
Heightened intrathecal release of proinflammatory cytokines in Creutzfeldt-Jakob disease.
The authors report high intrathecal release of tumor necrosis factor alpha (TNF-alpha) and interleukin (IL)-1beta in five patients with sporadic or new-variant Creutzfeldt-Jakob disease (CJD) without activation of the humoral or lymphocytic immune responses. Increased release of TNF-alpha and IL-1beta was also detected in some patients with progressive dementias. CJD is associated with a local cerebral host response that involves the release of proinflammatory cytokines.
Creutzfeldt-Jakob Syndrome↗
Tumor necrosis factor alpha stimulates lipolysis in adipocytes by decreasing Gi protein concentrations.
Prolonged treatment (12-24 h) of adipocytes with tumor necrosis factor alpha (TNFalpha) stimulates lipolysis. We have investigated the hypothesis that TNFalpha stimulates lipolysis by blocking the action of endogenous adenosine. Adipocytes were incubated for 48 h with TNFalpha, and lipolysis was measured in the absence or presence of adenosine deaminase. Without adenosine deaminase, the rate of glycerol release was 2-3-fold higher in the TNFalpha-treated cells, but with adenosine deaminase lipolysis increased in the controls to approximately that in the TNFalpha-treated cells. This suggests that TNFalpha blocks adenosine release or prevents its antilipolytic effect. Both N6-phenylisopropyl adenosine and nicotinic acid were less potent and efficacious inhibitors of lipolysis in treated cells. A decrease in the concentration of alpha-subunits of all three Gi subtypes was detected by Western blotting without a change in Gs proteins or beta-subunits. Gi2alpha was about 50% of control, whereas Gi1alpha and Gi3alpha were about 20 and 40% of control values, respectively. The time course of Gi down-regulation correlated with the stimulation of lipolysis. Furthermore, down-regulation of Gi by an alternative approach (prolonged incubation with N6-phenylisopropyl adenosine) stimulated lipolysis. These findings indicate that TNFalpha stimulates lipolysis by blunting endogenous inhibition of lipolysis. The mechanism appears to be a Gi protein down-regulation.
Adipocytes↗
CDKN2A variants in a population-based sample of Queensland families with melanoma.
BACKGROUND: Mutations in the CDKN2A gene confer susceptibility to cutaneous malignant melanoma (CMM); however, the population incidence of such mutations is unknown. Polymorphisms in CDKN2A have also been described, but it is not known whether they influence melanoma risk. We investigated the association of CDKN2A mutations and polymorphisms with melanoma risk in a population-based sample of families ascertained through probands with melanoma. METHODS: The 482 Queensland, Australia, families in our sample were characterized previously as having high, intermediate, or low family risk of CMM. Unrelated individuals (n = 200 families/individuals) drawn from the Australian Twin Registry served as control subjects. For individuals in the high-risk group, the entire CDKN2A gene coding region was screened for mutations by use of the polymerase chain reaction, agarose gel electrophoresis, allele-specific oligonucleotide (ASO) hybridization, and single-strand conformation polymorphism analysis. The intermediate- and low-risk families and control subjects were analyzed by ASO hybridization for a total of six recurring mutations as well as for polymorphisms at nucleotides (Nts) 442, 500, and 540. RESULTS: CDKN2A mutations were found only in the high-risk families (nine [10.3%] of 87). The prevalence of the Nt500G (guanosine) polymorphism increased linearly with increasing familial risk (two-sided P = .02) and was highest in the nine (primarily Celtic) families with CDKN2A mutations. After adjustment for ethnic origin, the relationship between risk group and the frequency of the Nt500G allele was weakened (P = .25); however, there was no relationship between ethnic origin and Nt500-polymorphism frequency among the control subjects. CONCLUSIONS: CDKN2A mutations are rare in this population (approximately 0.2% of all melanoma cases in Queensland) and appear to be associated with melanoma in only the most affected families. The Nt500G allele appears to be associated with familial risk, but this association probably reflects Celtic ancestry.
Autoradiography↗
Carbogen inhalation in cervical cancer: assessment of oxygenation change.
OBJECTIVE: Our objectives were (1) to examine tumor oxygenation measured with an Eppendorf pO(2) histograph, prior to and during carbogen (95% oxygen, 5% carbon dioxide) breathing in patients with primary cervical cancer; and (2) to assess the feasibility of delivering external beam radiation therapy and concurrent carbogen to patients treated for cervical cancer. METHODS: Pretreatment tumoral pO(2) measurements were obtained using an Eppendorf pO(2) histograph in patients with primary cervical cancers while breathing room air and after 4 min of carbogen breathing. Patients able to tolerate the carbogen inhalation were asked to inhale it for 4 min prior to and during all external beam radiation therapy. RESULTS: Two sets of pO(2) measurements were obtained from 25 patients. The average median pO(2) increased from 8 mm Hg when breathing room air to 96 mm Hg after carbogen breathing. Twenty-four of 25 patients tolerated the carbogen; they inhaled carbogen during their daily external beam radiation therapy. All 24 patients completed their planned course of external beam radiation therapy and daily concurrent carbogen without significant difficulty. CONCLUSION: (1) Carbogen inhalation increased the average median pO(2) value 10-fold and decreased the percentage of values </=2.5 and 5 mm Hg. (2) Carbogen inhalation is feasible during external beam pelvic radiation.
Administration, Inhalation↗
Indications and outcome of liver transplantation in tyrosinaemia type 1.
UNLABELLED: A retrospective analysis was performed on 17 patients presenting with tyrosinaemia type 1 (TT1) between 1989-1997; 7 pre 1992 prior to the introduction of 2-(2-nitro-4-trifluoromethylbenzoyl)-1, 3-cyclohexanedione (NTBC) therapy and 10 post 1992. During this time, eight children (5 males) underwent orthotopic liver transplantation (OLT); six prior to the introduction of NTBC in 1992 and two on NTBC therapy. The primary indications for OLT pre-1992 were risk of hepatocellular carcinoma with evidence of hepatic dysplasia in all, associated with liver failure in two, and rise in alpha-fetoprotein (AFP) in four. Two of the ten treated with NTBC required OLT. The indications were non-response to NTBC in one child and development of hepatic dysplasia associated with poor quality of life in the second patient. Median age for OLT was 64 months (range 5-127 months) with a median weight of 24 kg (range 6-25 kg). The histology of hepatectomy specimens at transplantation showed: cirrhosis in 8, hepatic dysplasia in 6 and hepatocellular carcinoma in 1. Plasma tyrosine and AFP returned to normal in all cases. Urinary succinylacetone reduced but persisted in small amounts (median 7.7 micromol/mmol creatinine). Hypertrophic cardiomyopathy resolved in 3/3 patients. Hypoglycaemia, not responding to dietary therapy or NTBC treatment, resolved post-transplant in one patient. There were two deaths, one from primary non-function and one from chronic rejection. Late complications in survivors (n=6) include post-transplant lymphoproliferative disease of the iris in one child which resolved and renal dysfunction with a fall in glomerular filtration rate in three (50%). Median follow up post OLT is 6.7 years (range 1-7 years). Quality of life post-transplant in survivors is good with unrestricted diet in all. CONCLUSION: Liver transplantation is an effective treatment for TT1 with good quality of life. The current indications of OLT in TT1 are non-response to NTBC, risk of malignancy and poor quality of life related to dietary restriction and frequency of blood sampling.
Adolescent↗
Calcium sensing properties of the GABA(B) receptor.
The GABA(B) receptor has been shown to consist of a heterodimer of two related 7-transmembrane receptors GABAB-R1 and GABA(B)-R2. These receptors share close homology to the Ca2+-sensing receptor and also to the metabotropic glutamate receptors, which have also been shown to respond to extracellular calcium. We show here that the GABA(B) receptor also has Ca2+ sensing properties. Ca2+ (0.001-1 mM) potentiated the GABA stimulation of [35S]GTPgammaS binding in membranes prepared from CHO cells stably expressing the GABA(B)-R1/R2 heterodimer. The GABA EC50 was reduced from 72 to 7.7 microM by addition of 1 mM Ca2+, with no change in the maximum response. A similar effect was observed in membranes from rat brain cortex. Ca2+ also potentiated GABA inhibition of forskolin-stimulated cAMP levels in the CHO cells and enhanced coupling to GIRK K+ channels in Xenopus oocytes. Other divalent cations were ineffective. The effects of Ca2+ were found to be agonist dependent with baclofen having a reduced sensitivity compared to GABA. Calcium appears to act allosterically to enhance GABA responses at the GABA(B) receptor, however, unlike the Ca2+-sensing receptor and some of the mGluR family, Ca2+ does not act as a ligand in its own right.
Amino Acid Sequence↗
Traumatic nerve injuries about the elbow.
Although not common, nerve injuries about the elbow occur because of the proximity of the three upper extremity nerves or because of the relationship of the median, ulnar, and radial nerves to the bony and soft-tissue structures about the elbow joint. Nerve injuries at and about the elbow joint occur more frequently with fractures than with any other kind of trauma. Nerve injuries may be found with periarticular fractures, dislocations, gunshot wounds, lacerations, and other iatrogenic causes.
Brachial Plexus↗
Health sector reform and the interpretation of policy context.
Health sector reform is on the policy agenda of national governments and international agencies. This paper focuses on the policy process of health sector reform and, more specifically, the policy context. The importance of understanding policy context is emphasised and the elements of policy context are discussed. These are: demographic and epidemiological change; processes of social and economic change; economic and financial policy; politics and the political regime; ideology, public policy and the public sector. The paper then discusses the means for, and methods of, interpretation of the policy context. Particular emphasis is placed on linking policy context with an overall understanding of the policy process, the 'messiness' of policy-making, the interrelationship between the contextual factors, the contextual factors interpreted by policy actors, the use of analytical categories in the policy analysis. The paper concludes on the importance of strengthening policy analysis for effective health sector reform.
Developing Countries↗