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Biomedical subjects

L Frost

Publications and source records attributed to L Frost.

At least 19 recordsLinked to original sources

Dynamics of urinary levels of hCG during early pregnancy and accuracy of the home pregnancy test.

The paper ‘Dynamics of urinary levels of hCG during early pregnancy and accuracy of the home pregnancy test’ has been retracted at the request of the authors. Since initiating the work 3 years ago improvements have been made to home pregnancy tests, and the device used in the study is no longer commercially available. The authors are conducting a similar study with a new pregnancy test device which suggests that some of the conclusions drawn in the retracted paper could now be misleading to health professionals and consumers.

Retraction of Publication as Topic↗

Elevated levels of WT1 transcripts in bone marrow harvests are associated with a high relapse risk in patients autografted for acute myeloid leukaemia.

Relapse postautograft in acute myeloid leukaemia (AML), may in part arise from leukaemia cells present in the bone marrow (BM) inoculum, and the level of minimal residual disease (MRD) in BM harvests used for autografting may therefore be clinically important. We have used the WT1 transcript as a marker of MRD, which was quantitated by RQ-PCR, in the BM harvests of 24 patients receiving an ABMT for AML. ABL was used as a control gene with WT1 level being normalised to 10(5) copies of ABL per sample. Median WT1 level was 651 copies (range=113-32 700) for the 13 patients with relapse-free survival (RFS) of less than 5 years, and 174 (range=0-1900) for patients with RFS of over 5 years postautograft (P<0.04). The RFS was 10.5 months for patients with WT1 level of >2000 copies (n=5), and has not yet been reached for patients with WT1 level<2000 (n=21), at a median follow-up of 92 months (P<0.05). We show that elevated levels of MRD in BM harvests are associated with a higher relapse risk in patients autografted for AML.

Acute Disease↗

Work related physical activity and risk of a hospital discharge diagnosis of atrial fibrillation or flutter: the Danish Diet, Cancer, and Health Study.

BACKGROUND AND AIMS: Excessive sporting activities have been associated with risk of atrial fibrillation. To study if work related physical activity also confers risk of atrial fibrillation or flutter, the association between work related physical strain and the risk of a hospital discharge diagnosis (inpatient as well as outpatient) of atrial fibrillation or flutter was examined. METHODS: A population based prospective cohort study was conducted from December 1993 to December 2001 among 19 593 men and 18,807 women with a mean age at baseline of 56 years (range 50-65 years) in the Danish Diet, Cancer, and Health Study. The physical strain during working hours was categorised as sedentary, light, or heavy, and analysed using proportional hazard models. Subjects were followed up in the Danish National Registry of Patients and in the Danish Civil Registration System. RESULTS: During follow up (mean 5.7 years) a hospital discharge diagnosis of atrial fibrillation or flutter occurred in 305 men and 113 women. When using the risk of atrial fibrillation or flutter associated with sedentary work at a sitting position as a reference, no excess risk (unadjusted as well as adjusted) was found of atrial fibrillation or flutter associated with sedentary work in a standing position, light workload, or heavy workload in men or women. CONCLUSION: No evidence was found of an association between physical activities during working hours and risk of a hospital discharge diagnosis of atrial fibrillation or flutter for men and women in the age group of 50-65 years.

Aged↗

Atrial fibrillation or flutter and stroke: a Danish population-based study of the effectiveness of oral anticoagulation in clinical practice.

OBJECTIVES: A pooled analysis of randomized trials has shown that oral anticoagulation therapy reduces the risk of ischaemic stroke with 68% in patients with atrial fibrillation. We examined the effectiveness of oral anticoagulation on risk of stroke of any nature (fatal and nonfatal ischaemic and/or haemorrhagic stroke) in patients with nonvalvular atrial fibrillation or flutter living in the County of North Jutland, Denmark. DESIGN: Cohort study. SUBJECTS AND METHODS: We used the Hospital Discharge Registry covering the county (490 000 inhabitants) from 1991 to 1998 to identify 2699 men and 2425 women with atrial fibrillation or flutter, aged 60-89 years. Data on prescriptions of anticoagulation were obtained from the National Health Service. We defined use of oral anticoagulation as date of prescription or reiteration plus 90 days. Patients were followed in the County Hospital Discharge Registry until a diagnosis of stroke (fatal and nonfatal ischaemic and/or haemorrhagic stroke), emigration, death or the end of 1998. We used Cox regression analyses to estimate the relative risk of stroke associated with use of oral anticoagulation compared with no use, adjusted for age, diabetes and underlying cardiovascular diseases. RESULTS: Eight hundred and thirty-eight of 2699 men (31%) and 552 of 2425 women (23%) with atrial fibrillation had one or more recorded prescriptions of oral anticoagulation. The incidence rates of stroke were 31 per 1000 person-years of follow-up in men, and 30 per 1000 person-years of follow-up in women. The adjusted relative risks of stroke during anticoagulation were 0.6 [95% confidence interval (CI) 0.4-1.0] in men, and 1.0 (95% CI 0.7-1.6) in women compared with nonuse periods. CONCLUSIONS: The effectiveness of oral anticoagulation in clinical practice may be lesser than the efficacy of oral anticoagulation reported from randomized trials.

Administration, Oral↗

Incident thromboembolism in the aorta and the renal, mesenteric, pelvic, and extremity arteries after discharge from the hospital with a diagnosis of atrial fibrillation.

BACKGROUND: The impact of atrial fibrillation (AF) on risk of peripheral arterial thromboembolism is unknown. METHODS: We analyzed the risk of thromboembolism (embolus and/or thrombosis) in the aorta and the renal, mesenteric, pelvic, and extremity arteries in a cohort of patients discharged from the hospital with an incident diagnosis of AF relative to the risk of thromboembolism in these vessels in the Danish population. In a random sample of half of the Danish population, 14 917 men and 14 945 women aged 50 to 89 years were identified in the Danish National Hospital Discharge Register with a diagnosis of AF from January 1, 1980, through December 31, 1993. Patients were followed up from diagnosis of AF in the Danish National Hospital Discharge Register and the Causes of Death Register until the first diagnosis of a thromboembolic event, death, or the end of 1993. Risk of a thromboembolic event relative to the risk in the Danish population was analyzed by means of Poisson regression modeling. RESULTS: Patients with a hospital diagnosis of AF had an increased risk of thromboembolic events in the aorta and the renal, mesenteric, pelvic, and extremity arteries (relative risk, 4.0 [95% confidence interval, 3.5-4.6] in men; and relative risk, 5.7 [95% confidence interval, 5.1-6.3] in women) compared with the Danish population. CONCLUSION: A hospital diagnosis of AF is an important risk factor for peripheral arterial thromboembolic complications.

Aged↗

The Picture Exchange Communication System.

The Picture Exchange Communication System (PECS) is an alternative/augmentative communication system that was developed to teach functional communication to children with limited speech. The approach is unique in that it teaches children to initiate communicative interactions within a social framework. This article describes the advantages to implementing PECS over traditional approaches. The PECS training protocol is described wherein children are taught to exchange a single picture for a desired item and eventually to construct picture-based sentences and use a variety of attributes in their requests. The relationship of PECS's implementation to the development of speech in previously nonvocal students is reviewed.

Audiovisual Aids↗

Processes and outcomes of training on rapid assessment and response methods on injecting drug use and related HIV infection in the Russian Federation.

In September 1997, Médecins Sans Frontières-Holland (MSF-H) began a project to provide training and support for HIV/AIDS prevention among injecting drug users (IDUs) in the Russian Federation, focusing on the use of the World Health Organization Rapid Assessment and Response Guide on Injecting Drug Use, and the European Peer Support Manual. As part of the training, participants are asked to carry out a rapid situation assessment (RSA) in their city or region as a major step towards designing and implementing an effective program to prevent HIV transmission among IDUs. This paper focuses on the first four training cycles of the programme (from January 1998 to January 1999), in which 89 health professionals and others from 32 Russian cities took part. A total of 28 rapid situation assessments were completed or almost completed by participants during these four cycles. The paper provides an overview of the methods used and major problems faced by participants undertaking these assessments, as well as summarising the 14 harm reduction programmes which resulted.

Journal Article↗

Incident stroke after discharge from the hospital with a diagnosis of atrial fibrillation.

PURPOSE: Atrial fibrillation is an important risk factor for stroke. We analyzed stroke risk over time in patients discharged from the hospital with a diagnosis of incident atrial fibrillation as compared with the risk of stroke in the Danish population. SUBJECTS AND METHODS: In a random sample of half of the Danish population, we identified 13,625 men and 13,577 women, aged 50 to 89 years, with a hospital diagnosis of atrial fibrillation and no prior diagnosis of stroke during 1980 to 1993. Data on other medical conditions were also available from 1977 to 1993, but medication data were not available. Patients were followed from the diagnosis of atrial fibrillation until the first diagnosis of stroke (nonfatal or fatal cerebral ischemic infarct and cerebral hemorrhage), death, or the end of 1993. The risk of stroke in these patients was compared with the risk in the Danish population using Poisson regression modeling to estimate relative risks (RR) and 95% confidence intervals (CI). RESULTS: For men with atrial fibrillation, the stroke rates increased by age, from 13 per 1,000 person-years in those ages 50 to 59 years, to 22 per 1,000 person-years in those ages 60 to 69 years, to 42 per 1,000 person-years in those ages 70 to 79 years, to 51 per 1,000 person-years in those ages 80 to 89 years. Age-specific stroke rates were similar in women with atrial fibrillation. Patients with a hospital diagnosis of atrial fibrillation had an increased risk of stroke (RR = 2.4; 95% CI, 2.3 to 2.5 in men and RR = 3.0; 95% CI, 2.9 to 3.2 in women) compared with the Danish population. Stroke risk was greatest during the first year after discharge and decreased thereafter. Hypertension, diabetes, and peripheral atherosclerosis were also associated with an increased risk of stroke among patients with atrial fibrillation. Ischemic heart disease and heart failure were risk factors in men only. There was no reduction in the risk of stroke from 1980 to 1993. CONCLUSIONS: Men and women with atrial fibrillation are at a substantially increased risk of stroke, particularly in the first year after the diagnosis.

Age Distribution↗

Dose-related cardiac electrophysiological effects of intravenous magnesium. A double-blind placebo-controlled dose-response study in patients with paroxysmal supraventricular tachycardia.

AIMS: The role of magnesium as an antiarrhythmic drug is yet not conclusive. Therefore, we performed a double-blind, randomized, placebo-controlled dose-response study of cardiac electrophysiological effects of intravenous magnesium. METHODS AND RESULTS: Thirty-six patients undergoing an electrophysiological evaluation for paroxysmal supraventricular tachycardia were randomized to one of the following dosages of intravenous magnesium (0, 5, 10 or 20 mmol). Conventional electrophysiological variables for sinus node function, atrial, atrioventricular node and ventricular conduction and refractoriness were measured before and after magnesium administration. Prolongation of the atrial-His interval was found at 5 mmol of magnesium compared with placebo and no further prolongation was observed at higher doses (-3 +/- 8, 11 +/- 9, 7 +/- 15, 11 +/- 16, for the dosages of 0, 5, 10 and 20 mmol of magnesium, respectively, P < 0.05). Measures of sinus node function, intra-atrial conduction and conduction through the Purkinje system were unaffected by magnesium. Male gender was associated with prolongation in atrial effective refractory period, in contrast to shortening in females: 2 +/- 43, 35 +/- 44, 36 +/- 33, 13 +/- 12 ms for males and 3 +/- 6, -12 +/- 11, -13 +/- 12, 0 +/- 23 ms for females, respectively (P < 0.001). CONCLUSION: Atrioventricular node conduction was prolonged by 5 mmol intravenous magnesium and no further prolongation was observed at higher dosages. At dosages of 5 and 10 mmol magnesium the atrial effective refractoriness was prolonged in males and shortened in females.

Adolescent↗

Decrease in mortality in patients with a hospital diagnosis of atrial fibrillation in Denmark during the period 1980-1993.

BACKGROUND: Atrial fibrillation is associated with increased mortality. We hypothesized that the death rate in atrial fibrillation patients in Denmark has diminished during the period 1980-1993. METHODS: In a random sample of half of the Danish population, 30 330 patients were found to have a diagnosis of incident atrial fibrillation in the Danish National Hospital Discharge Register 1980-1993. Information on previous and concomitant cardiovascular and metabolic diseases during the period 1977-1993 was sought in the register. The temporal trend in total and cardiovascular mortality in the cohort of atrial fibrillation patients was analysed. RESULTS: A significant decrease in total and cardiovascular mortality was seen, 12-13% for total mortality and 17-18% for cardiovascular mortality. By adjusting for the decreasing cardiovascular mortality rate in the general population, a decrease in the relative risk of total mortality of 8-13% with time was seen for the atrial fibrillation cohort, compared with the population risk, while no reduction in the relative risk of cardiovascular death was seen. CONCLUSION: A significant decrease in mortality with calendar period occurred in the cohort of atrial fibrillation patients.

Aged↗

Diagnostic accuracy with US: remote radiologists' versus on-site radiologists' interpretations.

PURPOSE: To compare the diagnostic accuracy of radiologists interpreting static ultrasonographic (US) images electronically transmitted to an academic medical center (remote radiologists) with that of radiologists performing "hands-on" US at a community-based outpatient site (on-site radiologists). MATERIALS AND METHODS: During 8 months, 80 patients underwent pelvic US at a community-based outpatient site. Images were electronically transmitted to a remote medical center as they were acquired at the community site and were printed on a laser printer identical to the one used at the outpatient site. The reference standard for correct diagnosis was based on histopathologic findings (n = 13), additional imaging results (n = 34), or review by a second independent observer (n = 33). Both an on-site and a remote radiologist interpreted the images, and their interpretations were rated as agree, both correct; agree, both incorrect; or disagree. Cases of disagreement were rated as major or minor. RESULTS: On-site and remote radiologists agreed in 69 of 80 patients (86%), and both radiologists were correct in all of these cases. There were 10 minor discrepancies and one major discrepancy. The diagnostic accuracies of the one-site and remote radiologists were 92% and 94%, respectively. CONCLUSION: High levels of diagnostic accuracy can be achieved by radiologists interpreting static US images. Strict protocols and excellent communication between the radiologist and sonographer are necessary to avoid diagnostic errors.

Academic Medical Centers↗

Late relapsing childhood lymphoblastic leukemia.

Childhood lymphoblastic leukemia (ALL) is usually assumed to have been permanently eradicated in patients in long-term remission, but occasionally can recur after many years. To learn more about the problem, we studied a group of children whose leukemia had been in remission for 10 or more years before relapse and tried to determine whether they had true recurrences or second malignancies. We studied children treated on Medical Research Council ALL protocols between 1970 and 1984 and followed up by the Clinical Trial Service Unit in Oxford. Detailed clinical and laboratory data was collected from the centers concerned on all who were reported to have had a recurrence of their leukemia after 10 or more years from the time of achieving first complete remission (CR1). To prove that the relapse was a true recurrence rather than a second or secondary leukemia, DNA extracted from archived marrow smears was subjected to polymerase chain reaction (PCR) analysis for the presence of an identical Ig heavy chain (IgH) or T-cell receptor (TCR) gene rearrangement at initial diagnosis and subsequent relapse. A total of 1,134 of 2,746 children had survived 10 years or more (range, 10 to 24 years) in CR1 and of those, 12 (approximately 1%) had subsequently relapsed. Relapse blast cells were shown to express the common ALL antigen (CD 10) in all cases and an identical clonal IgH or TCR gene rearrangement was found on PCR analysis of DNA from diagnosis and relapse in all eight cases where DNA extraction was successful. A further program of therapy was successful in inducing a second CR in all patients, four of whom have succumbed to a second relapse after 12 to 27 months. The remaining eight are in continuing CR2 at a follow-up of 12 to 108 months (median, 52) from relapse. Although the risk of relapse of childhood ALL after 10 years in remission appears to be small (around 1%), it persists. This raises questions about how blasts can survive quiescent for so long and when we can truly be confident of cure, if ever.

Adult↗

A novel and ubiquitous system for membrane targeting and secretion of cofactor-containing proteins.

We report the identification of the proteins encoded by the mttABC operon (formerly yigTUW), which mediate a novel Sec-independent membrane targeting and translocation system in Escherichia coli that interacts with cofactor-containing redox proteins having a S/TRRXFLK "twin arginine" leader motif. A pleiotropic-negative mutant in mttA prevents the periplasmic localization of twin arginine redox enzymes, including nitrate reductase (NapA) and trimethylamine N-oxide reductase (TorA). The mutation also prevents the correct localization of the integral membrane molybdoenzyme dimethylsulfoxide reductase (DmsABC). The DmsA subunit has a twin arginine leader. Proteins with a Sec-dependent leader or which assemble spontaneously in the membrane are not affected by this mutation. MttA, B, and C are members of a large family of related sequences extending from archaebacteria to higher eukaryotes.

2S Albumins, Plant↗

[From paroxysmal to chronic atrial fibrillation].

Chronic atrial fibrillation is by definition always preceded by paroxysmal atrial fibrillation. The electropathophysiological mechanisms underlying paroxysmal atrial fibrillation are reviewed: atrial electrophysiological inhomogeneity, atrial ectopic activity, and cardiac autonomic dysfunction. Safe and effective interventions that prevent the progression from paroxysmal into chronic atrial fibrillation have not yet been developed. Such developments should be given high priority, as the consequences of chronic atrial fibrillation--stroke and heart failure--are unacceptable.

Atrial Fibrillation↗

Comparison of bimanual examination with ultrasound examination before hysterectomy for uterine leiomyoma.

OBJECTIVE: To correlate the preoperative bimanual examination with ultrasound examination with regard to estimating the size of enlarged nongravid leiomyomatous uteri. METHODS: We performed a retrospective review of 161 patients who underwent hysterectomy for uterine leiomyoma between January 1994 and December 1994 and between July 1995 and April 1996. Uterine size was estimated clinically by bimanual examination. Ultrasound reports were reviewed. Uterine weights and dimensions in pathology reports were compared with findings on bimanual examination and ultrasonography. Body mass index (BMI) was calculated and patients were divided into two groups, one with BMIs of more than 30 and another with BMIs of less than or equal to 30. RESULTS: Ultrasound examination was ordered in 111 patients (68.9%) preoperatively. There was a strong correlation between the bimanual examination findings and the ultrasound dimensions. The equation for this relationship is ultrasound length (cm)=3.68 + 0.68 x number of weeks (r=.78, P < .001). Ultrasound length also was related strongly to size given in the pathologic reports; the equation for this relationship is ultrasound length (cm)=2.94 + 0.75 x pathology length (cm) (r=.73, P < .001). The correlation between bimanual examination and ultrasound findings was similar in obese and in nonobese patients, when uterine size could be estimated. CONCLUSION: There is a strong correlation between bimanual and ultrasound examinations with regard to determining the size of leiomyomatous uteri. Routine ultrasound is not indicated when an experienced examiner can assess uterine size. Ultrasonography may be appropriate when physical assessment is difficult, as in the case of obesity.

Body Mass Index↗

Selective phage infection mediated by epitope expression on F pilus.

Proteins and peptides can be displayed on bacterial and bacteriophage surfaces as fusions to bacterial integral membrane proteins or phage coat proteins. We now report on the expression of peptide antigens on the surface of F pili, elaborated by F+ strains of Escherichia coli. The peptides were expressed as fusions to F pilin, the building block of the F pilus that is encoded by the traA gene on the F plasmid. Filamentous bacteriophage infection of E. coli is normally mediated by phage binding to pilin at the F pili tip. Expression of 13 to 15 amino acid long peptides on the F pilus completely blocked infection by derivatives of wild-type infectious M13 phage. However, when a phage displaying a specific recombinant antibody fragment was allowed to interact with F pili displaying an antigenic peptide a bacterial infection could be demonstrated. This infection, mediated by the antibody-antigen interaction, resulted in bacterial cells containing plasmids encoding both the protein and the ligand. In a model library, where a scFv antibody against the human cytomegalovirus AD-2 epitope was selected we achieved an enrichment of 2500 of phage carrying the specific antibody, indicating an efficient selective infection.

Antibodies, Viral↗

A simplified preparation for relating cellular events to behavior: contribution of LE and unidentified siphon sensory neurons to mediation and habituation of the Aplysia gill- and siphon-withdrawal reflex.

We have begun to analyze several elementary forms of learning in a simple preparation consisting of the isolated mantle organs and abdominal ganglion of Aplysia. Previous studies suggested that plasticity at siphon sensory neuron synapses contributes to habituation and dishabituation of the gill- and siphon-withdrawal reflex in this preparation. We next wished to identify the sensory neurons that participate in the reflex and examine their plasticity more directly. To investigate the contribution of the LE siphon mechanosensory cells, we recorded from them and gill or siphon motor neurons during the same siphon stimulation that has been used in behavioral experiments in this preparation. Our results indicate that the LE cells make a substantial contribution to the evoked response in the motor neurons under these conditions, but they suggest that other as yet unidentified siphon sensory neurons with lower thresholds and shorter latencies also contribute. In addition, we find that homosynaptic depression of monosynaptic postsynaptic potentials (PSPs) from LE sensory cells makes an important contribution to habituation of the response in the motor neurons. To investigate plasticity of PSPs from the unidentified sensory neurons, we recorded the PSP that was produced in a motor neuron by water-movement stimulation of the siphon, which does not cause firing of LE cells. Our results suggest that PSPs from the unidentified sensory neurons and the LE neurons undergo similar plasticity during habituation and dishabituation training. These results support the idea that plasticity at synapses of both LE and unidentified sensory neurons contributes to habituation and dishabituation of the reflex response in this preparation.

Animals↗