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In re Finn.
HELD: State statute governing resuscitative decisions requires that (1) all persons be presumed to have capacity to make their own treatment decisions, and thus incapacity must be established by written determination of attending physician; failure to do so was sufficient basis to rescind DNR order requested by surrogate; (2) surrogate decision to request DNR order must be supported by the patient's current medical condition and fulfill statutory criteria; physicians' opinions regarding hypothetical future conditions and failure to support "medical futility" of treatment for patient did not support surrogate decision; and (3) statutory provision allowing surrogate to authorize DNR order on basis that resuscitative measures would pose an "extraordinary burden" for patient is unconstitutionally vague.
Conscious of a life in the balance: brain-injured man's divided family caught in legal, medical netherworld.
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Health technology assessment of PET in oncology: re Eur J Nucl Med Mol Imaging 2003; 30:637-641.
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Basal electrical impedance in relation to sodium lauryl sulphate-induced skin reactions--a comparison of patients with eczema and healthy controls.
BACKGROUND: Identification of subjects at risk for contact dermatitis by screening tests is desirable in order to adjust the preventive measures to individual skin susceptibility. The present study aimed to examine the effects of basic physiological features, such as baseline electrical impedance (IMP) and transepidermal water loss (TEWL), on reactivity to sodium lauryl sulphate (SLS). METHODS: On the basis of two previous studies, we re-evaluated the experimental irritant skin reactions (50 microL of 2% SLS in large Finn Chambers for 24 h) on the volar forearms of 29 patients with eczema and 19 healthy controls. RESULTS: We found definite differences in the baseline values of IMP, between the patients and the controls. Moreover, patients with eczema showed higher TEWL and lower MIX values on day 3 after exposure to SLS, which may indicate differences in SLS reactivity. After the study, the biophysical parameters of the eczema patients did not return to baseline, which suggests that their skin heals more slowly than that of normal subjects. CONCLUSIONS: Our findings indicate that the IMP technique may help to 'detect' chemically vulnerable skin. However, more studies are needed to determine the value of the basal electrical impedance parameters in assessing the risk of developing irritant contact dermatitis.
Assessment of balsam of Peru patch tests.
To find an ideal test technique for as low a dose of balsam of Peru (Myroxylon Pereirae) as possible, subjects testing positive to balsam of Peru are re-tested with a 25% concentration of balsam of Peru in petrolatum. Applications are with Finn Chambers for 6 different application times, and directly by foils for 96 h (4 days (D)). The goals are to confirm which subjects are positive and which are not, and, using that information, to see if it is possible to distinguish between these 2 groups, tested concomitantly at much lower serial dose levels, in terms of perfusion or by visual assessments. 5 different serial doses are applied with strips for 3-96 h (4D) and with foils for 96 h (4D). The Finn Chamber tests allow a distinction between visually positive and negative subjects supported by perfusion assessments. With the foils, a 24x lower serial dose level than with the 25% test substance is sufficient to distinguish between positive and negative subjects in terms of perfusion values. This approach requires readings up to 9 days. With this test, the visual approach yields only 3 of 10 positive subjects. This study demonstrates that a lower test dose is possible with perfusion assessments compared to visual ones.
Re: A simple, reliable method for fixation of percutaneous drainage catheters.
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Re: Small cell lung cancer treated in southeast Wales, Lester et al., Clin Oncol 2006;18:378-382.
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Prevalence and risk factors of squamous intraepithelial lesions of the cervix among HIV-infected women - a long-term follow-up study in a low-prevalence population.
HIV-infected women have high risk for precancerous lesions of the uterine cervix. We studied the prevalence and risk factors of squamous intraepithelial lesions (SIL) among systematically followed HIV-infected women enrolled from a population with low HIV prevalence. The study population consisted of 108 HIV-infected women enrolled between 1989 and 2003 with a mean follow-up 4.4 years. Risk factors of SIL were assessed based on samples collected during 2000-02. The overall rates of atypical glandular cells of uncertain significance (AGUS), atypical squamous cells of uncertain significance (ASCUS), low-grade SIL (LSIL) and high-grade SIL (HSIL) were 4, 24, 15 and 5%, respectively. Reduced CD4-lymphocyte count was associated with an increased prevalence of SIL, whereas duration of HIV infection (< or > or =5 years), use of antiretroviral medication, or HIV viral load (<50 or > or =50 copies/mL) was not. The cumulative risk of developing SIL after 1 and 5 years was 17% (95% confidence interval [CI] 7-27%) and 48% (95% CI 33-63%), respectively. The cumulative risk of SIL was increased among women younger than 31 years (P = 0.04) as well as in women displaying high initial HIV viral load (P = 0.01). Our results from a low HIV-incidence population re-emphasize the importance of guidelines for cytologic screening of HIV-seropositive women.
Search for bound states of the eta meson in light nuclei.
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Vaccine-induced protection against gastrointestinal bacterial infections in the absence of secretory antibodies.
Secretory IgA (SIgA) is widely held to be responsible for the defense of the mucosae against pathogenics and other potentially harmful agents. In this study, polymeric Ig receptor (pIgR) knockout mice, which lack secretory antibodies (SAb), were used to investigate the role of vaccine-elicited SAb in protection against gastrointestinal bacterial infections. An essential role for specific SAb in protection against Vibrio cholerae was evident from experiments showing that vaccinated pIgR(-/-) mice, but not vaccinated C57BL/6 mice, were susceptible to cholera toxin challenge. Vaccination of C57BL/6 mice with Salmonella typhimurium elicited strong antigen-specific, mucosal responses, which blocked in vitro invasion of epithelia. However, vaccinated C57BL/6 and pIgR(-/-) mice were equally resistant to challenge infection with virulent S. typhimurium. Finally, we investigated the importance of SIgA in protection against recurrent infections with Citrobacter rodentium. Although higher numbers of bacteria were detected early after challenge infection in feces of vaccinated pIgR(-/-) mice compared with vaccinated C57BL/6 mice, both mouse strains showed complete clearance after 9 days. These results suggested that, in immune animals, SIgA is crucial for the protection of gastrointestinal surfaces against secreted bacterial toxins, may inhibit early colonization by C. rodentium, but is not essential for protection against re-infection with S. typhimurium or C. rodentium.
Long-lived positron emitters zirconium-89 and iodine-124 for scouting of therapeutic radioimmunoconjugates with PET.
Antibody-PET imaging might be of value for the selection of radioimmunotherapy (RIT) candidates to confirm tumor targeting and to estimate radiation doses to tumor and normal tissues. One of the requirements to be set for such a scouting procedure is that the biodistributions of the diagnostic and therapeutic radioimmunoconjugates should be similar. In the present study we evaluated the potential of the positron emitters zirconium-89 ((89)Zr) and iodine-124 ((124)I) for this approach, as these radionuclides have a relatively long half-life that matches with the kinetics of MAbs in vivo (t(1/2) 3.27 and 4.18 days, respectively). After radiolabeling of the head and neck squamous cell carcinoma (HNSCC)-selective chimeric antibody (cMAb) U36, the biodistribution of two diagnostic (cMAb U36-N-sucDf-(89)Zr and cMAb U36-(124)I) and three therapeutic radioimmunoconjugates (cMAb U36-p-SCN-Bz-DOTA-(88)Y-with (88)Y being substitute for (90)Y, cMAb U36-(131)I, and cMAb U36-MAG3-(186)Re) was assessed in mice with HNSCC-xenografts, at 24, 48, and 72 hours after injection. Two patterns of biodistribution were observed, one pattern matching for (89)Zr- and (88)Y-labeled cMAb U36 and one pattern matching for (124)I-, (131)I-, and (186)Re-cMAb U36. The most remarkable differences between both patterns were observed for uptake in tumor and liver. Tumor uptake levels were 23.2 +/- 0.5 and 24.1 +/- 0.7%ID/g for the (89)Zr- and (88)Y-cMAb U36 and 16.0 +/- 0.8, 15.7 +/- 0.79 and 17.1 +/- 1.6%ID/g for (124)I-, (131)I-, and (186)Re-cMAb U36-conjugates, respectively, at 72 hours after injection. For liver these values were 6.9 +/- 0.8 ((89)Zr), 6.2 +/- 0.8 ((88)Y), 1.7 +/- 0.1 ((124)I), 1.6 +/- 0.1 ((131)I), and 2.3 +/- 0.1 ((186)Re), respectively. These preliminary data justify the further development of antibody-PET with (89)Zr-labeled MAbs for scouting of therapeutic doses of (90)Y-labeled MAbs. In such approach (124)I-labeled MAbs are most suitable for scouting of (131)I- and (186)Re-labeled MAbs.
Patch test responses to Malassezia pachydermatis in healthy dogs.
The effects of the patch test application of Malassezia pachydermatis extracts to normal canine skin were evaluated in eight healthy beagle dogs. Antigens (4 and 0.4 mg/ml) and saline controls were applied for 48 h using filter paper discs in Finn chambers. At the first test, two dogs showed patch test reactivity 20 min and 24 h after patch removal. Four out of six dogs that did not react to the first patch test showed reactivity when re-tested on day 8. Two remaining dogs were patch tested for a third time on day 15, after 7 days of cutaneous challenge with suspensions of M. pachydermatis cells, but failed to display reactivity. Positive patch test reactions were characterized histologically by mild epidermal hyperplasia, superficial dermal oedema and mild to moderate perivascular, periadnexal and interstitial infiltrates of neutrophils and CD3+ lymphocytes. Four dogs showed delayed intradermal test reactivity to M. pachydermatis antigens but intradermal and patch test reactivity did not correlate. This study indicates that patch test reactivity to M. pachydermatis antigen occurs in some healthy dogs exposed to the yeast, or may develop after a short period of antigen exposure. Further studies of patch test reactivity are warranted in dogs with disease associated with this cutaneous yeast.
To cope with uncertainty: stroke patients' use of temporal models in narratives.
Stroke victims have to cope with a disrupted autobiography and anxiety because of an uncertain future. Professionals share this uncertainty. The patients reveal their experiences in narratives, and when they try to regain coherence and confidence in life, they use narratives in the reconstructions. Because they have a temporal problem, time might be an important issue in these narratives. The aim of this study was to elucidate the use of time models in stroke patients' narratives. Nineteen stroke patients, who had recently been discharged to their homes after the stroke, accepted to participate in the study. Their age span was between 56 and 89 years. They had lived active urban lives before the stroke, and poststroke only three had more serious physical impairment, and none was demented. They were asked to talk about their present life and their conceptions of future life. The interviews were audio-taped and transcribed verbatim and narratives that referred to temporal aspects were thematically analysed with reference to narrative time models. The stroke accident had caused an autobiographical disruption and a temporal split because of a new awareness of human temporality and an uncertainty of the future. Confronted with these problems of time, the stroke victims constructed narratives based on the time models: time cycles and dissolution of time limits, exchange of time and exclusion from time. Hence, the time models worked as tools when the stroke victims re-established coherence in their present and future life. Stroke patients handled an uncertain future by using temporal models in their narratives. Professionals can support stroke patients by reinforcing these models.
Increasing use of medicines in elderly persons: a five-year follow-up of the Kuopio 75+Study.
OBJECTIVE: The aim of this study was to describe the changes in medicine use, polypharmacy and excessive polypharmacy between 1998 and 2003 among a cohort of elderly Finns. METHODS: For this prospective follow-up study, a random sample of 700 participants aged >or=75 years was drawn from the City of Kuopio, Finland. Of them, 601 participated in the study at baseline in 1998. The changes in medicine use among the survivors (n=339), who were re-examined in 2003, were recorded and are described here. Statistical significance of changes in medicine use was evaluated by Student's paired-samples and independent-samples t-test and Fisher's exact test. RESULTS: From 1998 to 2003, the mean number of medicines in use per individual increased from 6.3 to 7.5 (p<0.001). The prevalence of polypharmacy (>5 medicines in use) increased from 54% to 67% and excessive polypharmacy (>or=10 medicines in use) from 19% to 28%. The increase was due to increased use of regularly taken medicines, whereas the use of medicines taken as needed decreased during the follow-up in both sexes. At the time of follow-up survey, persons in institutional care used significantly more medicines (10.9) than community-dwelling elderly persons (7.0) (p<0.001). Central nervous system medicines and cardiovascular medicines were the most commonly used medicines in both years. CONCLUSION: The number of medicines and the prevalence of polypharmacy and excessive polypharmacy increases with advancing age. In order to avoid possible harmful effects and to optimize medication it is necessary to assess the medication regimen at regular intervals.
[Appendicitis and appendectomy in Norway 1990-2001].
BACKGROUND: The purpose of this study was to examine the incidence of appendicitis and appendectomy in Norway from 1990 to 2001. METHODS: Data were compiled from the Norwegian Patient Registry based on ICD-9 and ICD-10 codes for appendicitis and appendectomy. Re-admissions after appendectomy were selected based on institution and allocation numbers for hospitalisation. RESULTS: Age-adjusted incidence rates for appendectomy were 117 per 100 000 for men and 116 per 100 000 for women. Incidence rates were highest among patients aged 10-29. Diagnostic accuracy increased from 81% to 86% in men and from 60% to 71% in women over the study period. Perforation ratio increased from 12% to 21% in men and from 9% to 17% in women. Appendectomy by laparoscopic technique increased during 1998 to 2001 from 5% to 10% of cases for men and from 9% to 15% of cases for women. The proportion of laparoscopic appendectomy was considerably higher in two counties (50% and 28% in 2000-2001). Length of hospital stay was shorter after laparoscopy (median two days) than after open surgery (median three days), with no difference in the rate of re-admission of 4%. INTERPRETATION: Diagnostic accuracy and perforation ratio increased over the 1990s. Patients operated upon with laparoscopic technique had shorter hospital stays and the same re-admission rate compared to patients undergoing conventional surgery. Though the proportion of appendectomies done by laparoscopy doubled from 1998 to 2001, the procedure is not in commonly use in Norway.
Mimicking the events of menstruation in the murine uterus.
Menstruation and endometrial regeneration occur during every normal reproductive cycle in women and some Old World primates. Many of the cellular and molecular events of menstruation have been identified by correlative or in vitro studies, but the lack of a convenient model for menstruation in a laboratory animal has restricted functional studies. In this study, a mouse model for menstruation first described by Finn in the 1980s has been modified for use in a commonly used inbred strain of mouse. A decidual stimulus was applied into the uterine lumen of appropriately primed mice and leukocyte numbers and apoptosis were examined over time following progesterone withdrawal. Endometrial tissue breakdown was initiated after 12-16 h, and by 24 h, the entire decidual zone had been shed. Re-epithelialization was nearly complete by 36 h and the endometrium was fully restored by 48 h. Leukocyte numbers increased significantly in the basal zone by 12 h after progesterone withdrawal, preceding stromal destruction. Stromal apoptosis was detected by TUNEL staining at 0 and 12 h but decreased by 16 h after progesterone withdrawal. This mouse model thus mimics many of the events of human menstruation and has the potential to assist in elucidation of the functional roles of a variety of factors thought to be important in both menstruation and endometrial repair.
Epigenetic approaches to cancer therapy.
Histone deacetylation and DNA methylation have a central role in the control of gene expression, including transcriptional repression of tumour suppressor genes. Loss of DNA mismatch repair due to methylation of the hMLH1 gene promoter results in resistance to cisplatin in vitro and in vivo. The cisplatin-resistant cell line A2780/cp70 is 8-fold more resistant to cisplatin than the non-resistant cell line, and has the hMLH1 gene methylated. Treatment with an inhibitor of DNA methyltransferase, DAC (2-deoxy-5'-azacytidine), results in a partial reversal of DNA methylation, re-expression of MLH1 (mutL homologue 1) and sensitization to cisplatin both in vitro and in vivo. PXD101 is a novel hydroxamate type histone deacetylase inhibitor that shows antitumour activity in vivo and is currently in phase I clinical evaluation. Treatment of A2780/cp70 tumour-bearing mice with DAC followed by PXD101 results in a marked increase in the number of cells that re-express MLH1. Since the clinical use of DAC may be limited by toxicity and eventual re-methylation of genes, we suggest that the combination of DAC and PXD101 could have a role in increasing the efficacy of chemotherapy in patients with tumours that lack MLH1 expression due to hMLH1 gene promoter methylation.