Ampoule identification.
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Anesthetics, Intravenous↗
Biomedical subjects
J A Fleming
Publications and source records attributed to J A Fleming.
Effect of force direction on femoral fracture load for two types of loading conditions.
Identifying the loading conditions under which the femur is most likely to fracture may aid the prevention of hip fracture. This study quantified the effect of force direction on fracture load, a factor inherently associated with fracture risk. Finite element (FE) models of four femora were used to determine the force directions associated with the lowest fracture loads. Force directions were varied three-dimensionally for two types of loading, one representing impact from a fall and one similar to joint loading during daily activities (atraumatic loading). For the fall configuration, the force direction with lowest fracture load corresponded to an impact onto the posterolateral aspect of the greater trochanter. For atraumatic loading, the lowest fracture loads for the force directions analyzed occurred when posterior force components were relatively large or when posterior and lateral components were both small, similar to conditions while standing on one leg or climbing stairs. When both fall and atraumatic configurations are considered, the type of loading associated with greatest fracture risk, i.e., with the greatest applied force and lowest fracture load, is impact from a fall onto the posterolateral aspect of the greater trochanter. Therefore, evaluation of hip fracture risk and development of fracture prevention technologies should focus on this high-risk loading condition.
Accidental Falls↗
Cloning of the ovine estrogen receptor-alpha promoter and functional regulation by ovine interferon-tau.
Interferon-tau (IFNtau), the ruminant pregnancy recognition signal, inhibits transcription of the estrogen receptor alpha (ERalpha) gene in the endometrial lumenal epithelium of the sheep uterus, thereby abrogating production of luteolytic PGF(2alpha) pulses. The effects of IFNtau are mediated in part by IFN-stimulated response elements (ISREs) and IFN regulatory factor elements (IRFEs). The promoter/enhancer region of the ovine ERalpha gene was cloned, sequenced, and predicted to contain four IRFEs and one ISRE. Electrophoretic mobility shift assays indicated that the -2110 IRFE bound only IRF-1, whereas the -1877 IRFE and the -1284 ISRE were functional in binding IRF-1 and IRF-2. IFNtau inhibited transcriptional activity of the 2.7-kb ovine ERalpha promoter in transfection assays using ovine lumenal epithelium cells. Analyses of sequential 5'-deletion mutants of the ovine ERalpha promoter indicated that the effects of IFNtau may be mediated by IRFEs as well as other elements. Overexpression of ovine IRF-2, but not IRF-1, inhibited transcriptional activity of several regions of the ovine ERalpha promoter containing an IRFE or an ISRE as well as some, but not all, regions lacking these elements.
Animals↗
Function of tubulin binding proteins in vivo.
Overexpression of the beta-tubulin binding protein Rbl2p/cofactor A is lethal in yeast cells expressing a mutant alpha-tubulin, tub1-724, that produces unstable heterodimer. Here we use RBL2 overexpression to identify mutations in other genes that affect formation or stability of heterodimer. This approach identifies four genes-CIN1, CIN2, CIN4, and PAC2-as affecting heterodimer formation in vivo. The vertebrate homologues of two of these gene products-Cin1p/cofactor D and Pac2p/cofactor E-can catalyze exchange of tubulin polypeptides into preexisting heterodimer in vitro. Previous work suggests that both Cin2p or Cin4p act in concert with Cin1p in yeast, but no role for vertebrate homologues of either has been reported in the in vitro reaction. Results presented here demonstrate that these proteins can promote heterodimer formation in vivo. RBL2 overexpression in cin1 and pac2 mutant cells causes microtubule disassembly and enhanced formation of Rbl2p-beta-tubulin complex, as it does in the alpha-tubulin mutant that produces weakened heterodimer. Significantly, excess Cin1p/cofactor D suppresses the conditional phenotypes of that mutant alpha-tubulin. Although none of the four genes is essential for viability under normal conditions, they become essential under conditions where the levels of dissociated tubulin polypeptides increase. Therefore, these proteins may provide a salvage pathway for dissociated tubulin heterodimers and so rescue cells from the deleterious effects of free beta-tubulin.
Animals↗
Serum levels of soluble CD44 in primary Sjögren's syndrome.
OBJECTIVE: To determine whether elevated soluble CD44 (sCD44) levels serve as a marker of inflammation and lymphoproliferation in primary Sjögren's syndrome (SS). METHODS: We measured sCD44 levels by ELISA in serum samples from a cross section of healthy individuals and patients seen in a rheumatology clinic for evaluation of possible primary SS. RESULTS: Median serum levels of sCD44 were significantly higher in 48 healthy men compared to 52 healthy women (16 vs. 12 nmol/l; p = 0.0034). There was no relationship between serum levels of sCD44 and age or ethnic background. Slightly higher median levels of sCD44 were found in the serum of 37 women with primary SS compared to healthy women (14 vs. 12 nmol/l; p = 0.0402). However, these levels were comparable to those of 33 female patients without primary SS who were seen in the same clinic (p = 0.1233). CONCLUSION: Serum levels of sCD44 were slightly higher in female patients with primary SS compared to healthy women, but they are not likely to discriminate between patients with and without primary SS in a rheumatology practice.
Adult↗
Randomized, double-blind, placebo-controlled crossover trial of modafinil in the treatment of excessive daytime sleepiness in narcolepsy.
Seventy-five patients meeting international diagnostic criteria for narcolepsy enrolled in a 6-week, three-period, randomized, crossover, placebo-controlled trial. Patients received placebo, modafinil 200 mg, or modafinil 400 mg in divided doses (morning and noon). Evaluations occurred at baseline and at the end of each 2-week period. Compared with placebo, modafinil 200 and 400 mg significantly increased the mean sleep latency on the Maintenance of Wakefulness Test by 40% and 54%, with no significant difference between the two doses. Modafinil, 200 and 400 mg, also reduced the combined number of daytime sleep episodes and periods of severe sleepiness noted in sleep logs. The likelihood of falling asleep as measured by the Epworth Sleepiness Scale was equally reduced by both modafinil dose levels. There were no effects on nocturnal sleep initiation, maintenance, or architecture, nor were there any effects on sleep apnea or periodic leg movements. Neither dose interfered with the patients' ability to nap voluntarily during the day nor with their quantity or quality of nocturnal sleep. Modafinil produced no changes in blood pressure or heart rate in either normotensive or hypertensive patients. The only significant adverse effects were seen at the 400-mg dose, which was associated with more nausea and more nervousness than either placebo or the 200-mg dose. As little as a 200-mg daily dose of modafinil is therefore an effective and well-tolerated treatment of excessive daytime somnolence in narcoleptic persons.
Adult↗
Clinical, biochemical and pathological predictors of poor response to intravenous cyclophosphamide in patients with proliferative lupus nephritis.
BACKGROUND: Reports in the literature on the outcome of lupus nephritis (LN) treated with intravenous (i.v.) cyclophosphamide have varied considerably. Previous studies have suggested that less than 25% of patients with LN will progress to end stage renal failure (ESRD) after 5 years. In addition it has been reported that serum creatinine and chronic histologic changes on kidney biopsy are useful markers of renal prognosis. Whether treatment with cyclophosphamide alters the predictive value of these markers in LN patients is not clear. The aim of this study was to review our experience of treating a large cohort of patients with LN treated with i.v. cyclophosphamide and to identify biochemical and histological features at the time renal biopsy which predict outcome in these patients. DESIGN: We retrospectively reviewed our experience with 43 consecutive patients who met criteria for either World Health Organization (WHO) classification III (focal proliferative) or IV (diffuse proliferative) LN and were treated with monthly i.v. cyclophosphamide. Biochemical indices of renal function and lupus disease activity were recorded. Renal biopsies, performed within two months of commencing therapy, were reviewed by two experienced pathologists and classified according to WHO classification as well as activity and chronicity index. The primary outcome variable for the analysis was the development of ESRD. RESULTS: Patients were followed for a mean of 2 years after renal biopsy. The mean dose of cyclophosphamide received by patients was 8.3 g. One patient died during follow up and 22 (51%) progressed to ESRD. A higher serum creatinine (p = 0.003) and higher score for interstitial fibrosis (p = 0.001) were associated with shorter renal survival. There was no significant association between activity index or its components or in the total chronicity score and survival free from the need for dialysis. CONCLUSION: In our experience more than half of patients treated with i.v. cyclophosphamide for LN progress to ESRD and a high serum Cr and a high degree of interstitial fibrosis on renal biopsy before treatment are associated with a worse renal prognosis.
Adult↗
Lack of correlation between serum soluble Fas/APO-1 levels and autoimmune disease.
OBJECTIVE: To determine whether elevated soluble Fas/APO-1 (sFas/APO-1) levels are associated with either autoimmune disease or evidence of flares in autoimmune disease. METHODS: Thirty-seven serum samples were retrospectively obtained from normal controls and patients with laboratory evidence of autoimmune disease activity. These samples were assayed for sFas/APO-1 levels by an enzyme-linked immunosorbent assay, and hospital medical records were retrospectively reviewed for clinical and laboratory characteristics of the patients. RESULTS: Soluble Fas/APO-1 levels did not correlate with clinical diagnoses or laboratory abnormalities. The mean and range of sFas/APO-1 levels were similar in systemic lupus erythematosus patients (including those with active disease), patients with other autoimmune diseases, and normal controls. CONCLUSION: These data strongly suggest that measurement of sFas/APO-1 levels is unlikely to hold clinical value or play a role in the pathogenesis of autoimmune disease.
Adolescent↗
Toward a consensus: the synthesizing formulation.
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Canada↗
REM sleep abnormalities and psychiatry.
Since the 1950s, with the discovery of REM sleep and its relationship to dreaming, psychiatric sleep researchers have been interested in uncovering the complex relationship between disturbed sleep and psychiatric disorders. This paper reviews the alterations in REM sleep of relevance to psychiatry and indicates that continued developments in sleep research may assist in further understanding the neuropathophysiology of affective and other psychiatric illnesses.
Age Factors↗
The difficult to treat insomniac patient.
When a complaint of significant insomnia does not respond to standard interventions, the clinician must reassess the diagnosis with particular emphasis on psychiatric or psychological factors. This article describes the management of patients with 'sleeping pill insomnia,' insomnia associated with affective illness, sleep state misperception, 'sick role' behavior and treatment non-compliance.
Adult↗
Establishing the onset of psychotic illness.
OBJECTIVE: To date, the literature has provided no standardized, replicable method for establishing illness onset. The authors describe a method for dating the first appearance of prodromal signs of psychotic illness, the emergence of an acute episode, and the initiation of treatment seeking. METHOD: Using reports by family and friends about a sample of 141 subjects with first-episode psychosis, the investigators derived a checklist of behaviors describing the evolution of various phases of illness. Supplied with the checklist, clinician pairs independently rated the critical phases in the evolution of illness: first appearance of noticeable symptoms, first appearance of prominent psychotic symptoms, and initiation of treatment seeking. RESULTS: The judges achieved good reliability in assigning age at the first appearance of psychotic symptoms and at initiation of treatment seeking. Judging the beginning of the prodrome proved more difficult. Insidious onset proved as characteristic of affective psychosis as of schizophrenia, while treatment lag--the interval between emergence of acute psychotic symptoms and initiation of treatment seeking--was longer for schizophrenia than for affective psychosis. Onset of schizophrenia occurred earlier in women than in men. Depression with psychotic features appeared earlier in men than women. CONCLUSIONS: Although dating the onset of illness phases is probably feasible, efforts to improve reliability must continue. The study results challenge beliefs about gender differences in age at onset.
Adolescent↗
Propofol--rational and accurate reporting.
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Australia↗
The teaching of case formulation in Canada.
Prompted by the Council on Education and Professional Liaison of the Canadian Psychiatric Association, the authors surveyed the program directors and senior residents of departments of psychiatry on the teaching of case formulation skills in Canada. The results showed that case formulation is taught formally in most departments and that students are expected to demonstrate these skills throughout their training. However, less than one-half of the teaching programs provide guidelines for case formulation. The residents, who expected case formulation skills to be assessed in the oral examinations of the Royal College, were unanimous in their view that the process should be standardized and that guidelines be provided. Both the program directors and the residents favoured a biopsychosocial format for recording case formulation, but they did not agree on the content of an ideal formulation.
Curriculum↗
Sleep disturbance, depression, and lesion site in patients with multiple sclerosis.
We examined the prevalence of sleep problems in a sample of patients with mild but clinically definite multiple sclerosis (n = 143) and sought to determine whether there was a relationship between the presence of sleep complaints and the level of depression. As magnetic resonance imaging scans were available for a subsample of the patients with multiple sclerosis (n = 117), we also wanted to determine whether there was a relationship between the site of the lesion and the presence of sleep difficulties. The prevalence of sleep difficulties was three times higher in the patients with multiple sclerosis than the control group (25.2% vs 8.2%). Moreover, the presence of sleep complaints was associated with higher levels of depression. Three lesion sites that subserve supplemental motor areas were significantly related to the presence of sleep complaints. These findings suggest that, for some patients with MS, sleep disturbance and accompanying increases in depression may be a function of the lesion site resulting in nocturnal spasms.
Adult↗
Adenotonsillectomy for upper airway obstruction carries increased risk in children with a history of prematurity.
To define better the clinical presentation and perioperative outcome in children undergoing adenotonsillectomy (T&A) for relief of upper airway obstruction (UAO), we reviewed the hospital records of 60 consecutive, otherwise normal children aged 12 years or younger. Seven patients with trisomy 21, neurologic impairments, or preoperative cor-pulmonale were excluded. Intraoperative and postoperative complications were experienced by 15 (34%) and 13 (25%), respectively, of the 53 children with preoperative UAO. The most severe complications comprised pulmonary edema and prolonged postoperative oxyhemoglobin desaturation. Multivariate logistic regression analysis found a history of prematurity and/or low birth weight to be the most significant risk factors related to the occurrence of complications. Twenty-eight % of the study population had a history of prematurity and they had approximately 85% of the perioperative complications seen in children with UAO undergoing T&A. Other significant risk factors included adenoidal facies and evidence of respiratory distress at the time of surgery. It appears that T&A poses significant risk for children with UAO who were born prematurely and have evidence of abnormal facial development or respiratory distress preoperatively.
Adenoidectomy↗
Use of antianxiety drugs as countermeasures in the detection of guilty knowledge.
To evaluate whether antianxiety drugs enable guilty subjects to appear innocent on polygraph tests, we compared the effects of diazepam, meprobamate, and propranolol on the outcome of a guilty knowledge test (GKT). Seventy-five undergraduate students were evenly divided among one innocent and four guilty groups. Subjects in each of the guilty groups received either one of the drugs or a placebo prior to the administration of the GKT and after viewing a videotape that depicted a burglary as seen from the perspective of the burglar. The results showed that drug status had no influence on the outcome of the GKT. Innocent subjects who coincidentally obtained high scores on a recognition memory test covering details of the mock crime tended to obtain higher guilt scores on the GKT.
Adolescent↗
Cardiovascular and vasoactive hormone responses to bladder distension in spinal and normal man.
Many patients with high spinal cord injury experience exaggerated blood pressure rises in response to bladder distension. To examine the humoral mechanisms associated with these responses, ECG heart rate, blood pressure and vasoactive hormone levels were measured at baseline and during bladder distension following slow bladder filling in 23 subjects: 9 high spinal lesion patients, 7 low spinal lesion patients and 7 normal control subjects. Systolic blood pressure rose significantly during bladder distension in the high spinal lesion group by an average of 56 mm Hg (48%) and diastolic blood pressure rose by 22 mm Hg (47%), while heart rate fell by a mean of 7.4 beats per minute (15%). By contrast, neither systolic or diastolic blood pressure nor heart rate changed significantly during bladder distension in the low spinal lesion or normal control group. There were no significant changes in plasma levels of noradrenaline, renin, aldosterone, vasopressin, arginine, or atrial natriuretic peptide during bladder distension to account for the blood pressure rise in the high spinal lesion group. These findings suggest that humoral mechanisms are unlikely to play a major role in the mediation of pressor responses to bladder distension in high spinal lesion patients.
Blood Pressure↗