Continuous Holter telemetry of atrial electrograms and marker annotations using a common Holter recording system: impact on Holter electrocardiogram interpretation in patients with dual chamber pacemakers

The impact of continuous telemetry of atrial electrogram and marker annotations on Holter ECG interpretation was assessed in 98 patients with bipolar dual chamber pacemakers (VDD pacemakers n = 29, DDD(R) systems n = 69). Atrial electrogram and marker annotations were continuously sampled by a telemetry coil that was externally positioned on the pacemaker pocket, amplified, and transduced to a three-channel Holter ECG recorder in addition to an ECG recording. Holter tapes were analyzed by two experienced investigators for quality of P wave recognition and episodes suspicious of pacemaker dysfunction. Initially, only the ECG channel was analyzed. Thereafter, results were compared to those achieved on the basis of the complete recording including atrial electrogram and marker annotations. Recognition of atrial rhythm was markedly improved by Holter telemetry. During 99.3% of recording time telemetry showed a satisfying quality, whereas ECG alone allowed a reliable P wave recognition only during 84.4% of recording time (P < 0.001). One hundred twenty-nine episodes suspicious of pacemaker malfunction occurred in 17 of 98 patients. By analysis of ECG, only 78.3% of episodes were concordantly classified by the investigators. However, 98.4% of all episodes were properly identified when atrial electrogram and marker annotations were added to the analysis (P < 0.001). In particular, discrimination between atrial undersensing, sinus bradycardia, and atrial sensed events within the refractory periods was facilitated. Holter telemetry of atrial electrogram and marker annotations facilitates the analysis of Holter ECGs in pacemaker recipients and improves the detection of pacemaker dysfunctions.     

A new topical model of Staphylococcus corneal infection in the mouse

PURPOSE: To establish, in the scarified mouse eye, a new model of Staphylococcus aureus keratitis suitable for studies of pathogenesis and host defense mechanisms. METHODS: Corneas of three strains of mice (BALB/c, A/J, and C57BL/6) were scarified and inoculated with S. aureus strain 8325-4. Mice underwent slit lamp examination (SLE) at 1, 3, 5, 7, and 9 days after infection and were killed. Histopathologic analyses, determination of bacterial colony-forming units (CFU), and myeloperoxidase (MPO) activity assays were performed at each time point. RESULTS: S. aureus keratitis developed in both BALB/c and A/J strains of mice, but not in C57BL/6. The BALB/c and A/J strains demonstrated greater susceptibility to infection, as evidenced by significantly higher SLE scores and more viable bacteria per infected eye than in C57BL/6 mice at 5, 7, and 9 days after infection (P 相似文献   

Cognitive and neuroimaging predictors of instrumental activities of daily living.

Impaired ability to conduct daily activities is a diagnostic criterion for dementia and a determinant of healthcare services utilization and caregiver burden. What predicts decline in instrumental activities of daily living (IADLs) is not well understood. This study examined measures of episodic memory, executive function, and MRI brain volumes in relation to baseline IADLs and as predictors of rate of IADL change. Participants were 124 elderly persons with cognitive function between normal and moderate dementia both with and without significant small vessel cerebrovascular disease. Random effects modeling showed that baseline memory and executive function (EXEC) were associated with baseline IADL scores, but only EXEC was independently associated with rate of change in IADLs. Whereas hippocampal and cortical gray matter volumes were significantly associated with baseline IADL scores, only hippocampal volume was associated with IADL change. In a model including cognitive and neuroimaging predictors, only EXEC independently predicted rate of decline in IADL scores. These findings indicate that greater executive dysfunction at initial assessment is associated with more rapid decline in IADLs. Perhaps executive function is particularly important with respect to maintaining IADLs. Alternatively, executive dysfunction may be a sentinel event indicating widespread cortical involvement and poor prognosis.     

The effect of radiotherapy on dysphagia and survival in patients with esophageal cancer

A group of 127 patients with esophageal cancer treated with radiotherapy at different dose levels was retrospectively analysed. It was found that 70.5% of the patients showed improvement of dysphagia and that 54% remained palliated with respect to food passage until their death. The two major prognostic variables with respect to the palliative effect on dysphagia as well as survival were the passage score and the radiation dose. Patients with severe dysphagia (PASS 0 or 1) had a median actuarial DFI and SURV of 3.7 and 6.4 months, respectively, in contrast to 16.0 and 8.7 months for patients who were able to use (semi)solid food (PASS 2 and 3). The median actuarial DFI and SURV of patients treated with a relatively low dose (less than 50 Gy in 5 weeks) were 2.5 and 4.8 months, respectively, compared to 10.1 and 8.3 months, respectively, for patients treated with a relatively high dose.     

The predictive value of cell kinetic measurements in a European trial of accelerated fractionation in advanced head and neck tumors: an interim report

The value of cell kinetic measurements in head and neck tumors in predicting which patients will benefit from accelerated fractionation radiotherapy regimens is being tested in a multicenter European trial (EORTC trial 22851). This paper reports on the first analysis of the correlation of kinetics with outcome in this trial. A proportion of patients in both the accelerated arm (72 Gy in 5 weeks, 1.6Gy per fraction, 45 fractions) and the conventional arm (70-72 Gy in 7-8 weeks, 1.8-2.0 Gy per fraction, 35-40 fractions) were given an i.v. injection of 100 mg/m2 IUdR (iododeoxyuridine) before treatment, and a tumor biopsy was taken several hours later. The potential doubling time of the tumor (Tpot) was obtained from a flow cytometric analysis of tumor cell nuclei using an anti-IUdR antibody. From a total of 260 patients entered in the trial, 53 have undergone kinetic analysis. Adequate IUdR labeling was seen in 47 patients (88.7%), from which the mean value for Tpot was found to be 4.5 +/- 2.5 days (+/- S.D.). Of the IUdR labeled patients, 30 have now been followed up for at least 1 year, 17 with conventional and 13 with accelerated radiotherapy. These patients were split into those with fast and those with slowly growing tumors, the dividing line being the median Tpot value of 4.6 days. After conventional 7-week radiotherapy, 2 of 6 patients with "fast" growing tumors obtained local control compared with 8 of 11 with "slow" growing tumors. A small difference in local control was seen been fast and slow tumors in the accelerated arm (5/9 vs. 3/4). These preliminary data support the hypothesis that patients with fast growing tumors do poorly with conventional radiotherapy and that pretreatment kinetic measurements can select patients at risk. The predictive power of the method must await the final analysis of trial results.     

Associations between glaucomatous visual field loss and participation in activities of daily living

Purpose: This study investigated the association between visual field loss and participation in daily activities in individuals with glaucoma. Methods: Seventy‐nine patients were recruited from the Royal Victorian Eye and Ear Hospital. Visual fields were assessed using the Esterman binocular visual field tests and participation in daily activities was assessed using the Impact of Vision Impairment (IVI) questionnaire. Visual acuity and contrast sensitivity were also measured. Results: There was no independent relationship between visual field loss and IVI score (r = ?0.20; P = 0.09), except for the mobility domain (r = 0.25; P = 0.03). Mobility was the most affected domain of the IVI (mean = 1.2). Over a quarter of the patients reported experiencing moderate to severe restriction with mobility activities despite relatively minor binocular field loss. Conclusion: Mobility is the area in which glaucoma patients encounter difficulties even when the visual field and visual acuity are relatively good. Questions related to mobility could be asked to identify those patients who need rehabilitation.     

Associations between two common variants C677T and A1298C in the methylenetetrahydrofolate reductase gene and measures of folate metabolism and DNA stability (strand breaks, misincorporated uracil, and DNA methylation status) in human lymphocytes in vivo.

OBJECTIVE: Homozygosity for variants of the methylenetetrahydrofolate reductase (MTHFR) gene is associated with decreased risk for colorectal cancer. We have investigated the relationships between two variants of the MTHFR gene (C677T and A1298C) and blood folate, homocysteine, and genomic stability (strand breakage, misincorporated uracil, and global cytosine methylation in lymphocytes) in a study of 199 subjects. RESULTS: The frequencies of homozygosity for the C677T and A1298C variants of the MTHFR gene were 12.6% and 14.6%, respectively. Plasma homocysteine, folate, vitamin B12, 5-methyltetrahydrofolate, and RBC folate were determined in the C677T genotypes. Plasma folate was significantly lower (P < 0.001) in the homozygous variants (6.7 +/- 0.6 ng/mL) compared with wild-types (8.8 +/- 0.4 ng/mL) and heterozygotes (9.1 +/- 0.5 ng/mL). Homocysteine was significantly higher (P < 0.05) in homozygous variants (13.2 +/- 1.1 micromol/L) compared with homozygous subjects (10.9 +/- 0.4 micromol/L). Homozygous variants had significantly lower (P < 0.05) RBC folate (84.7 +/- 6.3 ng/mL) compared with wild-types (112.2 +/- 5.2 ng/mL) and heterozygous individuals (125.1 +/- 6.6 ng/mL). No significant difference in RBC folate was observed between wild-types and heterozygotes. The A1298C variant did not influence plasma homocysteine, folate, 5-methyltetrahydrofolate, vitamin B12, or RBC folate. Lymphocyte DNA stability biomarkers (strand breaks, misincorporated uracil, and global DNA methylation) were similar for all MTHFR C677T or A1298C variants. CONCLUSION: Data from this study do not support the hypothesis that polymorphisms in the MTHFR gene increase DNA stability by sequestering 5,10-methylenetetrahydrofolate for thymidine synthesis and reducing uracil misincorporation into DNA.     

Immunochemotherapy with rituximab and temozolomide for central nervous system lymphomas

BACKGROUND: Methotrexate-based and alkylator-based chemotherapy regimens are associated with renal and bone marrow toxicities, which limit their use in patients with central nervous system (CNS) lymphomas. The authors report their experience with an immunochemotherapy regimen consisting of rituximab and temozolomide in patients with primary or metastatic CNS lymphoma. METHODS: Seven patients who had received rituximab and temozolomide were identified from the database of the brain tumor clinic at the authors' institution: three patients had developed recurrent primary CNS lymphoma (PCNSL), one patient had newly diagnosed PCNSL but had poor renal function, and three other patients with systemic non-Hodgkin lymphoma developed recurrent lymphoma in the brain only. Patients were scheduled to receive 4 cycles of induction rituximab on Day 1 and temozolomide on Days 1-5 of a 28-day cycle. Thereafter, their treatment included a total of up to 8 maintenance cycles of temozolomide alone on Days 1-5 of a 28-day cycle. A gadolinium-enhanced magnetic resonance image of the head was obtained after every two cycles of treatment. RESULTS: All patients received rituximab without toxicity. Of the 4 patients who received induction temozolomide at doses > 150 mg/m(2) daily on Days 1-5, 2 experienced Grade 2 leukopenia and thrombocytopenia. Five patients achieved a radiographic complete response, and two patients had partial responses after induction treatment. The median response duration was 6 months (range 3-12+ months), and the median survival was 8 months (range 3+-12+ months). CONCLUSIONS: Although median survival was short, immunochemotherapy with rituximab and temozolomide was well tolerated and exhibited efficacy in this elderly and heavily pretreated cohort. The data obtained in the current study suggest that the optimal induction dose combination consists of rituximab 375 mg/m(2) on Day 1 and temozolomide 150 mg/m(2) daily on Days 1-5.     

Cancer mortality in relatives of women with breast cancer: The OPCS study

Mortality from cancer and other causes in male and female first-degree relatives of women with breast cancer diagnosed before age 60 has been examined in a large population-based cohort study, providing estimates of familial risks free from ascertainment or recall bias. Relatives of 3,295 patients with breast cancer diagnosed in the UK between 1954 and 1981 were identified through a register of households established in 1939. The 11,678 first-degree relatives thus identified were followed up through national records until the end of 1992. Over this period 5,421 deaths (including 1,527 cancer deaths) occurred in these relatives. Mortality from breast cancer was significantly raised in first-degree relatives (SMR 187, 248 deaths), and there was also significant excess mortality from cancers of the larynx (SMR 177, 17 deaths), endometrium (SMR 166, 29 deaths) and unspecified neoplasms (SMR 153, 70 deaths). The SMR for ovarian cancer was 130, based on 58 deaths (p = 0.06). There was no marked excess for other sites or for non-neoplastic causes of death, but there was a significant deficit in mortality from cervical cancer (SMR 63, 18 deaths). The SMR for breast cancer increased significantly with decreasing age of the relative. After allowing for age, sisters of cases had a slightly (though non-significantly) higher risk than mothers (ratio of SMRs 1.22). These results, together with penetrance estimates from linked families, suggest that approximately one woman in 800 carries BRCAI, the susceptibility gene on chromosome 17q, and that this gene causes about 1% of all breast cancers. © 1996 Wiley-Liss, Inc.     

Perturbations in cortical development and neuronal network excitability arising from prenatal exposure to benzodiazepines in mice

During brain development, many factors influence the assembly and final positioning of cortical neurons, and this process is essential for proper circuit formation and normal brain function. Among many important extrinsic factors that guide the maturation of embryonic cortical neurons, the secreted neurotransmitter GABA has been proposed to influence both their migratory behaviour and their terminal differentiation. The full extent of the short‐term and long‐term changes in brain patterning and function caused by modulators of the GABA system is not known. In this study, we specifically investigated whether diazepam, a commonly used benzodiazepine that modulates the GABA_A receptor, alters neuronal positioning in vivo, and whether this can lead to lasting effects on brain function. We found that fetal exposure to diazepam did not change cell positioning within the embryonic day (E)14.5 mouse cerebral cortex, but significantly altered neuron positioning within the E18.5 cortex. In adult mice, diazepam treatment affected the distribution of cortical interneurons that express parvalbumin or calretinin, and also led to a decrease in the numbers of calretinin‐expressing interneurons. In addition, we observed that neonatal exposure to diazepam altered the sensitivity of mice to a proconvulsant challenge. Therefore, exposure of the fetal brain to benzodiazepines has consequences for the positioning of neurons and cortical network excitability.