Optimal positive end-expiratory pressure fails to preserve nonrespiratory lung function in acute lung injury.
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Biomedical subjects
Publications and source records attributed to L Fisher.
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Transgenic mice (ND4) containing 70 copies of the transgene encoding DM20 were clinically normal up to 3 months of age, spontaneously demyelinated there-after and died in 8-10 months. Whereas the myelin fraction from normal mice increased in amount from 1-4 months as expected, the corresponding fraction in ND4 mice remained constant over this period. In order to study the mechanism by which decreased myelin synthesis was manifest in the ND4 mouse, we investigated the amounts of proteolipids at various ages. The amount of proteolipid protein (PLP) was greatly decreased after 1-2 months in the ND4 mice. Although the message for DM20 was increased (transgene mRNA), very little DM20 was found in myelin at 1 month. It subsequently increased so that at 3-4 months the amount of DM20 in myelin isolated from transgenic animals was much higher than in normal mice. Characterization of the DM20 and PLP at 1 month of age showed that the amount of fatty acid (stearate and palmitate) was increased and the N-terminal glycine was methylated. These data suggested that high copy numbers of the cDNA for DM20 affected post translational events which we postulate affected the proper insertion of both DM20 and PLP in the myelin bilayer.
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Bone sialoprotein (BSP), a secreted glycoprotein found in bone matrix, has been implicated in the formation of mammary microcalcifications and osteotropic metastasis of human breast cancer (HBC). BSP possesses an integrin-binding RGD (Arg-Gly-Asp) domain, which may promote interactions between HBC cells and bone extracellular matrix. Purified BSP, recombinant human BSP fragments and BSP-derived RGD peptides are shown to elicit migratory, adhesive, and proliferative responses in the MDA-MB-231 HBC cell line. Recombinant BSP fragment analysis localized a significant component of these activities to the RGD domain of the protein, and synthetic RGD peptides with BSP flanking sequences (BSP-RGD) also conferred these responses. The fibronectin-derived RGD counterpart, GRGDSP (Gly-Arg-Gly-Asp-Ser-Pro), could not support these cellular responses, emphasizing specificity of the BSP configuration. Although most of the proliferative and adhesive responses could be attributed to RGD interactions, these interactions were only partly responsible for the migrational responses. Experiments with integrin-blocking antibodies demonstrated that BSP-RGD-induced migration utilizes the alpha(v)beta3 vitronectin receptor, whereas adhesion and proliferation responses were alpha(v)beta5-mediated. Using fluorescence activated cell sorting, we selected two separate subpopulations of MDA-MB-231 cells enriched for alpha(v)beta3 or alpha(v)beta5 respectively. Although some expression of the alternate alpha(v) integrin was still retained, the alpha(v)beta5-enriched MDA-MB-231 cells showed enhanced proliferative and adhesive responses, whereas the alpha(v)beta3-enriched subpopulation was suppressed for proliferation and adhesion, but showed enhanced migratory responses to BSP-RGD. In addition, similar analysis of two other HBC cell lines showed less marked, but similar RGD-dependent trends in adhesion and proliferation to the BSP fragments. Collectively, these data demonstrate BSP effects on proliferative, migratory, and adhesive functions in HBC cells and that the RGD-mediated component differentially employs alpha(v)beta3 and alpha(v)beta5 integrin receptors.
Ethylmalonic encephalopathy (EE), an organic aciduria of unknown etiology characterized by developmental delay, hypotonia, and vascular instability associated with lactic acidemia and urinary excretion of ethylmalonic acid (EMA) and methylsuccinic acid (MSA), has been described in 11 patients. To test the possibility that the underlying biochemical defect involves isoleucine catabolism, we determined the response to oral L-isoleucine (IIe) load (150 mg/kg) in a 5-year-old girl with EE and in three healthy, age- and sex-matched controls. Following IIe load in the patient, there was accumulation of 2-methylbutyrylglycine (2-MBG) and a delayed and lower peak urinary excretion of tiglylglycine (TGL), suggesting a partial defect in 2-methyl-branched chain acylcoenzyme A dehydrogenase (2M-BCAD). In vitro measurements 2M-BCAD activity in cultured skin fibroblasts from patients with EE have been reported to be normal. Our results show that isoleucine is a source for the elevated EMA and MSA in patients with EE, and suggest a functional, possibly secondary, deficiency of activity of 2M-BCAD in vivo.
A structure-activity study of compounds related to NKA was performed using uterus from the oestrogen-primed rat, a preparation thought to contain a significant population of NK2 receptors. The compounds tested included: NKA and its C-terminal fragments; NKA(4-10)-free acid; a series of LAla monosubstituted analogues of NKA(4-10) and of NKA; [DAla1]NKA; and a series of analogues of [Nle10]NKA(4-10) monosubstituted at position four, five or seven. Results suggest that the His at position one of NKA is of little or no importance in contractile activity, while substitution or truncation of Lys at position two or substitution of Thr at position three causes a decrease in potency. Results also confirm that amino acids at positions four, six, seven, nine and ten are very important for contractile activity of NKA and its analogues on rat uterus. The similarity between the changes in potency obtained in this study, and those obtained in rabbit pulmonary artery, an NK2 monoreceptor preparation, provides further evidence for the presence of NK2 receptors in the uterus of the oestrogen-primed rat.
This study investigated whether performance on the card playing task (Newman, Patterson, & Kosson, 1987) and the moral/conventional distinction measure predict level of childhood conduct problems as indexed by the Psychopathy Screening Device (Frick & Hare, in press). The card-playing task indexes the child's sensitivity to changes in reinforcement rate. The moral/conventional distinction measure indexes the child's sensitivity to the difference between moral transgressions which result in harm to another from conventional transgressions which more usually result in social disorder. The Psychopathy Screening Device indexes a behavioral syndrome that consists of two dimensions: affective disturbance and impulsive and conduct problems. Thirty-nine children with emotional and behavioral difficulties were presented with both measures. Performance on both measures did predict extent of behavioral disturbance. Moreover, there was a significant association between performance on the card playing tasks and the moral/conventional distinction. The results are interpreted within the response set modulation and violence inhibition mechanism models and by reference to recent work at the anatomical level.
A literature review indicated that suicidal behavior in Sudan was very infrequent. However, an assessment of suicidal ideation in two Sudanese groups of women demonstrated high levels, particularly in women in a displaced-persons area. In addition, the recent establishment of a Befrienders International volunteer service allowed anecdotal evidence of substantial suicidal behavior to be collated. These findings highlight the need for further professional and volunteer assistance with continuing evaluation and research concerning programs for this vulnerable population.
To describe family context in health research, the authors tested a typology of families developed in California with a sample of families in Quebec, Canada. Family scales from the California study were submitted to focus groups, translated, and standardized on a sample of 209 parents. A panel of experts then revised the scales to make them relevant to Quebec families and to health promotion. Data from the new and revised scales were collected on 509 Quebec couples (1,018 spouses) and were clustered separately by gender, using K means. The procedure classified all respondents into family types that paralleled the original typology. Discriminant analyses indicated that family profile variables significantly distinguished family types. Comparisons with family, stress, and health variables further differentiated among the types and expanded their meaning. The study demonstrates a method for redefining and extending family data in health research with different cultural groups.
BACKGROUND: We report a clinical trial which evaluated the effectiveness of triple therapy containing low- and high-dose azithromycin to treat Helicobacter pylori infection. METHODS: From March 1997 to March 1998, patients infected with H. pylori were assigned to receive either: Treatment 1: ranitidine bismuth citrate (RBC) (400 mg b.d.) and amoxycillin (1 g b.d.) for 10 days with azithromycin 500 mg o.m. for 3 days: or Treatment 2: RBC and amoxycillin for 10 days with azithromycin 1 g o.m. for 3 days. H. pylori eradication was established by a urea breath test at least 4 weeks after therapy. Side-effects and compliance were assessed using a diary. RESULTS: Sixty-eight patients were enrolled. Fifty-seven per cent of patients were treated for active peptic ulcer disease or a history of peptic ulcer disease. Treatment 1 cured H. pylori in 44% and 44% by per protocol and intention-to-treat analysis, respectively. The corresponding eradication rates for Treatment 2 were 79% and 75%. Two patients taking Treatment 2 dropped out of the study because of side-effects. CONCLUSIONS: With RBC and amoxycillin for 10 days, azithromycin at a dose of 1 g/day for 3 days was significantly better at curing H. pylori infection than azithromycin 500 mg/day for 3 days.
A composite measure of subclinical vascular disease has been developed in the Cardiovascular Health Study (CHS). In previous reports, we measured the prevalence of subclinical disease among the original 5201 participants in the CHS, the relationship of risk factors to subclinical disease, and the association of subclinical disease to clinical coronary heart disease. In 1992 to 1993 (year 4 of the study), a larger cohort of 424 black women and 248 black men was added to the study. In this study, we have compared the prevalence of subclinical disease among blacks and whites in the CHS and the association with cardiovascular risk factors. The prevalence of subclinical disease for all participants (aged > or =65 years) was 41.3% for white women, 39.7% for black women, 41.9% for white men, and 43.7% for black men. The prevalence increased with age. The risk factor associations for subclinical disease were similar among blacks and whites. In multivariate analysis, age, systolic blood pressure, LDL cholesterol, smoking, and family history of myocardial infarction were independently associated with subclinical disease among both black and white women, while for white men, systolic blood pressure, use of antihypertensive medication, smoking, body mass index, and diastolic blood pressure (inverse) were related to subclinical disease. In black men, blood triglyceride level, use of antihypertensive medications, and family history of myocardial infarction (inverse) were associated with subclinical disease.
Interactions among the brain, the pituitary gland, and the adrenal glands (i.e., the hypothalamic-pituitary-adrenal [HPA] axis) help regulate the body's response to stress. The adrenal hormone cortisol plays a key role in stress reduction through its effects on multiple body systems. Excessive cortisol activity during both chronic alcohol administration and withdrawal may underlie some of the clinical complications of alcoholism, including increased risk of infectious diseases; bone, muscle, and reproductive system changes; altered energy metabolism; and disorders of mood and intellect. Despite excessive cortisol levels during intoxication and withdrawal, however, the HPA axis becomes less responsive to stress during abstinence, potentially resulting in an impaired capacity to cope with relapse-inducing stressors.
HYPOTHESIS: The primary purpose of this study was to determine if children, > or =5 years old, with onset of deafness before the acquisition of spoken language (i.e., prelingually deafened) derived more benefit from multichannel cochlear implants than from conventional hearing aids. It was hypothesized that children who used oral communication (speech plus listening) would demonstrate higher levels of performance after implantation than children who used total communication (English sign system plus speech and listening). BACKGROUND: Previous research suggests that prelingually deafened children given implants at an older age derive limited benefit from these devices. Changes in candidacy criteria and advances in technology, however, may make cochlear implants a more viable treatment option for this group of patients. METHODS: A repeated-measures design was to used to compare patients' preoperative performance with hearing aids to postoperative performance with the CLARION cochlear implant after 3 and 6 months of device use. Pre- and postoperative performance were analyzed separately for children who used oral and total communication. RESULTS: Both groups of children (oral and total communication) demonstrated significant postoperative improvement on all outcome measures over time. Postoperative scores of the children who used oral communication were significantly higher than those of the children who used total communication on four of the five outcome measures. CONCLUSIONS: Prelingually deafened children who do not receive cochlear implants until > or =5 years of age derive significant benefit from current implant devices compared with that obtained with conventional hearing aids. The greatest benefit is derived by children who use oral communication, with much more limited benefit demonstrated by children who use total communication.
Some nurses have the goal to lead others and to be in charge of patient groups and groups of staff. They want to make changes at the upper levels of the organization and see their actions affect large numbers of people. Many others, however, really desire to be a bed-side nurse giving excellent patient care. They want to enjoy the close relationship that can make an individual feel better about him or her self as a person and the satisfaction that they have made a difference in one person's life. However, whether the nurse leads through a management position or practices leadership techniques in bedside nursing, all nurses are leaders and need to demonstrate expertise in the use of leadership techniques.
Falls are of particular concern in psychiatric hospitals where many patients are taking psychotropic medication that may produce postural hypotension. The research considered falls in a private psychiatric hospital before and after the introduction of a hospital policy to measure blood pressure, both lying and standing, after a patient had fallen. Falls, and the injuries associated with them, occurred predominantly among elderly patients. The results of the study showed that the introduction of the policy resulted in more frequent measurement of blood pressure and was associated with fewer repeat falls.
The uterotonic potencies of the naturally occurring mammalian tachykinins and the synthetic subtype-selective agonist analogues of these agents [Lys5,MeLeu9,Nlel0]neurokinin A-(4-10) and [Nle10]neurokinin A-(4-10) (tachykinin NK2 receptor-selective), [Sar9,Met(O2)11]substance P (tachykinin NK1 receptor-selective) and senktide (tachykinin NK3 receptor-selective) were determined using preparations from oestradiol-treated rats. The endopeptidase 24.11 inhibitor, N-[N-[1-(S)-carboxyl-3-phenylpropyl]-(S)-phenyl-alanyl-(S)-isoserine+ ++ (SCH 39370), potentiated responses to neurokinin A, neurokinin B and substance P, but not to [Lys5,MeLeu9,Nle10)]neurokinin A-(4-10) or senktide. [Nle10]neurokinin A-(4-10) effects were potentiated by SCH 39370 with amastatin and those to [Sar9,Met(O2)11]substance P were potentiated by SCH 39370 and captopril in combination. In the presence of optimal concentrations of peptidase inhibitors the relative order of agonist potency was: neurokinin A > substance P > neurokinin B for the naturally occurring mammalian tachykinins and [Lys5,MeLeu9,Nle10]neurokinin A-(4-10) > [Nle10]neurokinin A-(4-10) > [Sar9,Met(O2)11]substance P > senktide for the synthetic tachykinin analogues. Thus, while a tachykinin NK2 receptor predominates in the oestrogen-primed uterus, a tachykinin NK1 receptor may also be present. The non-peptide tachykinin NK3 receptor antagonist, SR 142801, did not antagonise the effects of senktide suggesting that tachykinin NK3 receptors do not mediate its relatively minor effect on the uterus of the oestrogen-primed rat.