Preimplantation B-type natriuretic peptide concentration is an independent predictor of future appropriate implantable defibrillator therapies.

OBJECTIVE: To assess prospectively whether preimplantation B-type natriuretic peptide (BNP) and C reactive protein (CRP) concentrations predict future appropriate therapies from an implantable cardioverter-defibrillator (ICD). DESIGN AND SETTING: Prospective cohort study conducted in a tertiary cardiac care centre. METHODS: 345 consecutive patients undergoing first time ICD implantation were prospectively studied. Serum BNP and CRP concentrations were obtained the day before ICD implantation. Patients were followed up with device interrogation to assess for appropriate shocks or antitachycardia pacing. Inappropriate therapies were excluded. Mean (SD) follow up was 13 (5) months. RESULTS: Patients had ischaemic (71%), primary dilated (17%), and valvar or other cardiomyopathies (12%). About half (52%) had ICDs implanted for primary prevention. Sixty three (18%) received appropriate ICD therapies. Serum creatinine, beta blocker, statin, and angiotensin converting enzyme inhibitor usage did not differ between therapy and no therapy groups. By univariate comparison, ejection fraction (p = 0.048), not taking amiodarone (p = 0.033), and BNP concentration (p = 0.0003) were risk factors for ICD therapy. However, by Cox regression multivariate analysis, only BNP above the 50th centile was a significant predictor (hazard ratio 2.19, 95% confidence interval 1.07 to 4.71, p = 0.040). Median BNP was 573 ng/l versus 243 ng/l in therapy and no therapy patients, respectively (p = 0.0003). More patients with BNP above the 50th centile (27% v 10%, p = 0.006) received ICD therapies. CONCLUSIONS: A single preimplantation BNP concentration determination is independently predictive of ICD therapies in patients with cardiomyopathies undergoing first time ICD implantation. CRP was not independently predictive of ICD therapies when compared with BNP.

Hematopoietic cell transplantation in older patients with hematologic malignancies: replacing high-dose cytotoxic therapy with graft-versus-tumor effects.

Toxicities have limited the use of allogeneic hematopoietic cell transplantation (HCT) to younger, medically fit patients. In a canine HCT model, a combination of postgrafting mycophenolate mofetil (MMF) and cyclosporine (CSP) allowed stable allogeneic engraftment after minimally toxic conditioning with low-dose (200 cGy) total-body irradiation (TBI). These findings, together with the known antitumor effects of donor leukocyte infusions (DLIs), led to the design of this trial. Forty-five patients (median age 56 years) with hematologic malignancies, HLA-identical sibling donors, and relative contraindications to conventional HCT were treated. Immunosuppression involved TBI of 200 cGy before and CSP/MMF after HCT. DLIs were given after HCT for persistent malignancy, mixed chimerism, or both. Regimen toxicities and myelosuppression were mild, allowing 53% of eligible patients to have entirely outpatient transplantations. Nonfatal graft rejection occurred in 20% of patients. Grades II to III acute graft-versus-host disease (GVHD) occurred in 47% of patients with sustained engraftment. With median follow-up of 417 days, survival was 66.7%, nonrelapse mortality 6.7%, and relapse mortality 26.7%. Fifty-three percent of patients with sustained engraftment were in complete remission, including 8 with molecular remissions. This novel allografting approach, based on the use of postgrafting immunosuppression to control graft rejection and GVHD, has dramatically reduced the acute toxicities of allografting. HCT with the induction of potent graft-versus-tumor effects can be performed in previously ineligible patients, largely in an outpatient setting. Future protocol modifications should reduce rejection and GVHD, thereby facilitating studies of allogeneic immunotherapy for a variety of malignancies. (Blood. 2001;97:3390-3400)

Effect of alpha-oligosaccharide phenotype of Neisseria gonorrhoeae strain MS11 on invasion of Chang conjunctival, HEC-1-B endometrial, and ME-180 cervical cells.

The genes encoding the glycosyltransferases responsible for the addition of the five sugars in the alpha-oligosaccharide (alpha-OS) moiety of lipooligosaccharide (LOS) have been identified. Disruption of these glycosyltransferase genes singly or in combination results in corresponding truncations in LOS. In the present work we show that sequential deletion of the terminal four sugar residues of gonococcal alpha-OS had no discernible effect on the invasion of human conjunctival, endometrial, and cervical cell lines. However, deletion of the proximal glucose, which resulted in the complete deletion of alpha-OS, significantly impaired invasion of the gonococci into all three cell lines. The effect of deleting alpha-OS on invasion was independent of and additive to the known invasion-promoting factor OpaA. These data suggest that the proximal glucose residue of the alpha-OS chain of LOS is required for efficient invasion of gonococci into host mucosa.

The "Atlas of genetics and cytogenetics in oncology and haematology" on the internet and a review on infant leukemias.

The "Atlas of Genetics and Cytogenetics in Oncology and Haematology" (URL: http://www.infobiogen.fr/services/chromcancer) is a database devoted to chromosome abnormalities in cancer, cancer-prone diseases, and genes involved in cancer. The information is concise and updated. This database is made for and by cytogeneticists, molecular biologists, clinicians in oncology and hematology, and pathologists, who are encouraged to contribute. The database is herein presented, together with an example concerning congenital leukemias.

Atlas of genetics and cytogenetics in oncology and haematology, an interactive database.

The 'Atlas of Genetics and Cytogenetics in Oncology and Haematology' (http://www.infobiogen.fr/services/chromcancer ) is a database devoted to chromosome abnormalities in cancer, cancer-prone diseases and genes involved in cancer. Information presented in each page is concise and updated. This database is made for and by: cytogeneticists, molecular biologists, clinicians in oncology and in haematology, and pathologists, who are encouraged to contribute.

Polyunsaturated fatty acids inhibit the expression of the glucose-6-phosphate dehydrogenase gene in primary rat hepatocytes by a nuclear posttranscriptional mechanism.

Expression of the glucose-6-phosphate dehydrogenase (G6PD) gene is inhibited by the addition of polyunsaturated fatty acids to the medium of primary hepatocytes in culture. To define the regulated step, we measured the abundance of G6PD mRNA both in the nucleus and in total RNA and measured the transcriptional activity of the G6PD gene. Insulin and glucose stimulated a 5- to 7-fold increase in G6PD mRNA in rat hepatocytes. This increase was attenuated by 60% due to the addition of arachidonic acid. These changes in mRNA accumulation occurred in the absence of changes in the rate of transcription. Amounts of precursor mRNA (pre-mRNA) for G6PD in the nucleus changed in parallel with the amount of mature mRNA. The decrease in G6PD pre-mRNA accumulation caused by arachidonic acid was also observed with other long chain polyunsaturated fatty acids but not with monounsaturated fatty acids. In addition, this decrease was not due to a generalized toxicity of the cells due to fatty acid oxidation. These changes in G6PD expression in the primary hepatocytes are qualitatively and quantitatively similar to the changes observed in the intact animal due to dietary carbohydrate and polyunsaturated fat. Regulation of G6PD expression by a nuclear posttranscriptional mechanism represents a novel form of regulation by fatty acids.

Moderating effects of physical abuse and perceived social support on the potential to abuse.

This study investigated the moderating effects of perceived prepubertal social support on the relationship between prepubertal childhood physical abuse and child abuse potential as well as on the relationship between a childhood history of abuse and conflict and depth in adult relationships. Three hundred and sixty-nine undergraduate men and women were classified as abused or nonabused based on their responses to the Childhood History Questionnaire. Multiple regression analyses revealed interactions of social support and a childhood history of physical abuse on both the potential to abuse and the quality of participants' relationships with their parents. Differences between abused and nonabused individuals were obtained only under conditions of low perceived social support. When social support was perceived to be high, abused and nonabused individuals did not differ in the potential to abuse or in the ratings of the depth of their relationships with parents. Implications of these findings for the intergenerational transmission of abuse are discussed.

Use of back belts in occupational settings.

Studies of the biomechanical and physiological mechanisms of action concerning the prophylactic use of back belts to prevent occupational low back injuries are limited in number and present conflicting findings. The epidemiological data concerning the efficacy of back belts in the prevention of occupational low back injuries are not sufficient to warrant general use of back belts in the occupational setting for uninjured workers. There is actually a potential for increasing the degree of low back injury with general application of back belts in occupational settings. In sum, there are insufficient data in the scientific literature to indicate that general use of back belts in occupational settings is appropriate for uninjured workers. Because the increase in use of soft canvas back belts has been fairly recent, physical and epidemiological studies pertaining specifically to soft canvas back belts are extremely limited. The sample size of many physical investigations also is extremely limited. In many instances, studies concerning the role of back belts in preventing occupational low back injuries have examined conditions that do not apply directly to the use of soft canvas back belts. For these reasons, further studies in both the physical and epidemiological realms are necessary before it is appropriate to use commonly constructed back belts as personal protective equipment in occupational settings.

Relationship of plantar-flexor peak torque and dorsiflexion range of motion to kinetic variables during walking.

BACKGROUND AND PURPOSE: Limited ankle plantar-flexor moments and power during walking have been documented in several patient populations and are believed to contribute to gait deviations. The primary purpose of this study was to determine the relationship of plantar-flexor peak torque (PFPT) and dorsiflexion range of motion (ROM) to peak ankle moments and power during walking in a group of subjects without diabetes mellitus (DM) and in a group of subjects with DM and associated peripheral neuropathies. SUBJECTS: Nineteen subjects, 9 with DM and associated peripheral neuropathies (mean age = 58 years, SD = 14, range = 35-75 years) and 10 without DM (mean age = 57 years, SD = 11, range = 37-68 years), were evaluated. METHODS: The following data were collected on all subjects: PFPT, dorsiflexion ROM, and ankle moments and power during walking (using a two-dimensional link-segment model). Hierarchical multiple regression was used for data analysis. RESULTS: Plantar-flexor peak torque made substantial contributions to the ankle moment (40%) and ankle plantar-flexor power (53%) during walking. There also was a high correlation between PFPT and dorsiflexion ROM (r = .78) and between dorsiflexion ROM and ankle power (r = .72). CONCLUSION AND DISCUSSION: Plantar-flexor peak torque and dorsiflexion ROM are interrelated and appear to be important factors that contribute to ankle plantar-flexor moments and power during walking. This finding suggests that increasing PFPT and dorsiflexion ROM may help decrease gait deviations such as decreased step length and walking speed. When increasing PFPT is not possible, the natural occurrence of limited dorsiflexion ROM may help to maximize ankle moments during walking. Further research is needed to test whether these proposed treatment strategies can have a clinically useful effect. [Mueller MJ, Minor SD, Schaaf JA, et al. Relationship of plantar-flexor peak torque and dorsiflexion range of motion to kinetic variables during walking.

Low molecular weight heparin in prevention of restenosis after angioplasty. Results of Enoxaparin Restenosis (ERA) Trial.

BACKGROUND: Heparin, an anticoagulant, possesses antiproliferative effects and has been shown to reduce neointimal proliferation and restenosis following vascular injury in experimental studies. METHODS AND RESULTS: The primary aim of this double-blind multicenter study was to determine if 40 mg Enoxaparin, a low molecular weight heparin, administered subcutaneously once daily for 1 month after successful angioplasty would reduce the incidence of restenosis. Four hundred fifty-eight patients were randomized at nine clinical centers (231 to placebo and 227 to Enoxaparin). The primary end point was angiographic or clinical restenosis. Angiographic restenosis was defined as a loss of 50% of the initial gain as measured by quantitative coronary angiography (QCA) at a core laboratory. In the absence of QCA, clinical evidence of restenosis was defined as death, myocardial infarction, repeat revascularization, or worsening angina. Using the intention-to-treat analysis for all patients, restenosis occurred in 51% of the placebo group and 52% of the Enoxaparin group (relative risk, 1.07, P = .625). Likewise, no difference in restenosis was evident when the change in minimal lumen diameter or other angiographic definitions of restenosis were used. Adverse clinical events were infrequent and did not differ between the groups with the exception of minor bleeding complications, which were more common in the Enoxaparin group. CONCLUSIONS: Enoxaparin (40 mg/d SC for 1 month) following successful angioplasty did not reduce the incidence of angiographic restenosis or the occurrence of clinical events over 6 months. The treatment was well tolerated, although in-hospital minor bleeding was more common with active treatment.

Differences in the gait characteristics of patients with diabetes and peripheral neuropathy compared with age-matched controls.

BACKGROUND AND PURPOSE: Patients with diabetes and peripheral neuropathy have a high incidence of injuries while walking. Biomechanical analysis of their walking may lead to treatments to reduce these injuries. The purpose of this study was to compare (1) the gait characteristics, (2) the plantar-flexor peak torques, and (3) the ankle range of motion of subjects with diabetes mellitus (DM) and peripheral neuropathy with those of age-matched controls. SUBJECTS: Twenty subjects, 10 with DM and a history of peripheral neuropathy (DM group) (mean age = 58 years, SD = 15, range = 35-75) and 10 subjects without diabetes (NODM group) (mean age = 57 years, SD = 11, range = 37-68), were evaluated. METHODS: The following data were collected on all subjects: ankle joint mobility, plantar-flexor peak torque (ankle strength), kinematics of the trunk and lower extremity during normal walking, and ground reaction forces. Moments and power at the ankle, knee, and hip during walking were calculated using a two-dimensional link-segment model. RESULTS: The DM group subjects showed less ankle mobility, ankle moment, ankle power, velocity, and stride length during walking than the NODM group subjects. A significant decrease in ankle strength and mobility appeared to be the primary factor contributing to the altered walking patterns of the DM group. CONCLUSION AND DISCUSSION: The DM group subjects appeared to pull their legs forward using hip flexor muscles (hip strategy) rather than pushing the legs forward using plantar-flexor muscles (ankle strategy), as seen in the NODM group subjects. Implications for treatment are presented to attempt to reduce the number of injuries during walking in patients with DM and peripheral neuropathy.

Amiprilose hydrochloride inhibits porcine aortic smooth muscle cell proliferation in vitro.

The effect of amiprilose hydrochloride, a synthetic monosaccharide, on smooth muscle cell proliferation was studied in vitro. Using porcine aortic smooth muscle cell cultures, amiprilose significantly inhibited cell proliferation in a dose-dependent fashion at concentrations of 0.5-1.0 mg/ml. This antiproliferative effect was reversible upon removing amiprilose by cell washing and adding fresh media. Pretreating cells with amiprilose before serum stimulation did not affect subsequent growth. Inhibition of proliferation occurred when amiprilose was added up to 48 hours after serum stimulation. As such, amiprilose deserves further investigation as a potential therapeutic agent in preventing restenosis after angioplasty.

Representational-momentum effects in the cerebral hemispheres.

On each trial, after three squares of different sizes (inducing display) were sequentially presented at central fixation, a target square was briefly lateralized to the right or left hemisphere (RH or LH) of 24 normal right-handed males. Subjects determined whether or not the target differed in size from the third inducing square. Half of the targets that differed were consistent with size changes in the inducing display (e.g., a target smaller than the third square in an inducing display presented in a large-to-small order) and half were inconsistent. Three retention intervals (RIs) between offset of third inducing square and onset of target were used. At the shortest RI, error-rate differences in responding to consistent vs. inconsistent targets, i.e., representational-momentum (RM) effects, were larger in the RH than in the LH, and RM effects in the RH, but not in the LH, were affected by RI.

Enalapril in the prevention of restenosis following intracoronary intervention in a swine model.

BACKGROUND: Restenosis following percutaneous transluminal coronary angioplasty continues to be a major limitation of the procedure. To test whether an angiotensin-converting enzyme inhibitor may reduce restenosis, this study utilized an atherosclerotic, stented, Hanford miniature swine model of restenosis. METHODS: Each animal first was started on an atherogenic diet and had balloon abrasion of the left anterior descending and right coronary arteries. Four months later, balloon-mounted coil stents were placed into the abraded coronary arteries of each animal. Twenty-four animals then were randomly assigned to one of two groups: enalapril, and control. The enalapril group received 50 mg orally twice daily starting 1 week before intracoronary stenting. RESULTS: Follow-up 2 months later revealed angiographic stenosis in the control group of 30% +/- 13%/25% +/- 10% (left anterior descending/right coronary artery) versus 37% +/- 9%/20% +/- 11% in the enalapril group (P = not significant). The change in minimal lumen diameter from immediately after stenting to follow-up was not significantly different between control and enalapril groups. Area stenosis and maximal intimal thickness obtained by morphometric analysis were also compared, and the mean percentage area stenosis for the control group was 39 +/- 12%/31% +/- 16% and for enalapril 36% +/- 14%/35% +/- 19%. The maximal intimal thickness in the control group was 573 microns +/- 204 microns/605 microns +/- 266 microns and in the enalapril group 530 microns +/- 220 microns/424 microns +/- 237 microns. There was no statistical difference. CONCLUSIONS: Enalapril fails to reduce restenosis in this animal model.

Rotational ablation of coronary artery lesions using single, large burrs.

Previous clinical use of the Rotablator in coronary artery disease has involved a sequential increase in burr sizes up to 2 mm in diameter and has often utilized balloon adjunct to achieve an optimal result. We report our experience and describe our technique using a single, large burr (2.25, 2.5, or 2.75 mm diameter) without balloon assistance. The burr size was selected to approximate 70-90 percent of the apparent normal lumen diameter. Thirty-one patients with 36 lesions of complex morphology (eccentric, irregular, calcified, ulcerated, at bends, at bifurcations, completely occluded, as well as balloon failures) were successfully treated with the Rotablator. Results were assessed by computerized quantitative angiography. The percent diameter stenosis (mean +/- SD) for the group was reduced from 69.8 +/- 11.3% to 30.9 +/- 10% (p less than 0.001). The mean absolute diameter stenosis increased from 0.9 +/- 0.3 mm to 2.2 +/- 0.3 mm (p less than 0.001). Angiographically visible dissections were seen in 4 patients and were uncomplicated in 2. One patient had a non-Q-wave myocardial infarction. A fourth patient had a presumed acute occlusion 36 hr after the procedure, necessitating emergency bypass surgery, but without Q waves on the electrocardiogram or wall-motion abnormalities on the echocardiogram. Nitroglycerin was infused through the Rotablator catheter and has considerably lowered the degree and frequency of spasm. No other acute complications occurred. The mean procedure time using a single burr was shorter than when multiple burrs were used: 56.5 vs. 97.3 min, respectively (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

A study of discomfort with electrical stimulation.

The primary purpose of this study was to investigate the influence of personality variables and contractile forces on magnitude estimates of pain unpleasantness and pain intensity during varying levels of neuromuscular electrical stimulation (NMES). Thirty volunteers, according to their scores on a preferred coping-style questionnaire, were assigned to one of two groups, one designated "monitors" (information seekers) and the other designated "blunters" (information avoiders). All subjects were administered varying levels of two types of NMES, one causing both afferent stimulation and muscle contraction and one causing only afferent stimulation. Subjects judged the intensity and unpleasantness of each current type using magnitude estimation. Data were analyzed using a 2 x 2 x 2 x 3 (coping style x current type x pain descriptor x current level) analysis of variance. The results indicated that the rate of increase of magnitude estimates for unpleasantness and pain intensity that corresponded to increases in current were dependent on (1) the preferred coping style of the subject, (2) whether the stimulus caused a muscle contraction, and (3) whether the subject was judging the intensity or the unpleasantness of the applied stimulus. Behavioral styles appear to affect how subjects characterize the discomfort associated with NMES, and involuntary muscle contractions contribute to the discomfort felt from NMES. These results suggest that interventions tailored to a preferred coping style may increase a subject's level of tolerance to NMES and thus provide a more beneficial treatment.

The coronary artery response to implantation of a balloon-expandable flexible stent in the aspirin- and non-aspirin-treated swine model.

Intracoronary stents may potentially alleviate some of the problems associated with coronary angioplasty. Since the anatomy and physiology of swine coronary arteries closely resemble those of humans, the response to implantation of the Glanturco-Roubin, balloon-expandable, flexible stent was studied in this model. Additionally, the effect of aspirin, 1 mg/kg/day orally, on this response was evaluated. Eighteen Hanford minature swine underwent stenting of the left anterior descending coronary artery. Two died within 24 hours of stent implantation. The 16 survivors were put to death at 4 (n = 4), 11 (n = 4), 28 (n = 4), 56 (n = 3), and 180 (n = 1) days. Angiographically, reduction of stent lumen diameter of 0.1 to 1.3 mm was observed and was maximum at 11 days, with gradual improvement at subsequent time periods. Scanning electron microscopy, transmission electron microscopy, and light microscopy showed early disruption of subjacent endothelium, and adherence of platelets to exposed subendothelium and stent wires. Microthrombi were readily apparent. At 11 days, intimal thickening, made up predominantly of smooth muscle cells with abundant extracellular matrix, was observed and covered the stent wires. At 28 days, regression of intimal thickening was apparent and a confluent endothelium with flow-directed orientation was seen. At 56 and 180 days, the luminal surface was smooth; intimal thickening averaged 525 microns over the stent wires and 55 microns away from the wires. Findings in aspirin-treated animals were similar to results in those that did not receive aspirin. Thus in this swine model, stent implantation results in a time-dependent and self-limited vascular response.

Factors determining improvement in left ventricular function after reperfusion therapy for acute myocardial infarction: primacy of baseline ejection fraction.

Improvement in left ventricular ejection fraction is a measure of salvage of ischemic myocardium after reperfusion therapy for acute myocardial infarction. The degree of improvement in left ventricular ejection fraction may be influenced by many factors. Therefore, 137 patients in whom paired radionuclide angiograms were obtained within 24 h of acute infarction and before hospital discharge were retrospectively evaluated to determine which factors most affect improvement in ejection fraction. Only baseline ejection fraction correlated significantly with improvement in ejection fraction by both univariate analysis (ejection fraction as a continuous variable; p less than 0.001; ejection fraction as a categorical variable, less than or equal to 45% versus greater than 45%, p less than 0.0001) and multivariate analysis (p less than 0.0001). Reperfusion status (patent versus occluded infarct artery) and extent of coronary artery disease (one, two or three vessel) were significant factors by multivariate but not by univariate analysis. Location of infarction, treatment modality and time to treatment did not correlate with change in ejection fraction by either statistical technique. Thus, of those factors tested, baseline left ventricular ejection fraction is the most potent predictor of improvement in ventricular function after acute infarction. Knowledge of baseline ejection fraction may be helpful in deciding whether to treat some patients with equivocal indications or contraindications for reperfusion therapy. Clinical trials of reperfusion strategies should stratify patients on the basis of baseline ejection fraction if ejection fraction is to be used as an end point for myocardial salvage.