Biomedical subjects
Publications and source records attributed to A Cohen.
A pilot of item-of-service payments (85 Pounds per annum per patient) to general practitioners for monitoring long-term mentally ill individuals was successful in recruiting practices and ensuring assessments. It did not, however, demonstrate an improvement in health care.
Myocarditis is a focalised or diffuse disease of the myocardium. The principal causal agents are viruses in Europe and North America and a parasite in South America (Chagas' disease). The prevalence of acute myocarditis is variable, related to the periodic cycle of viral epidemics. The diagnosis is difficult to establish because the clinical presentation is variable, ranging from asymptomatic forms to rapidly fatal acute congestive heart failure. The diagnostic tools suffer from lack of sensitivity or specificity. Endomyocardial biopsy, despite its low sensitivity, remains the reference investigation as it provides histological proof of the myocarditis. Myocardial scintigraphy with antimyosin antibodies has the advantage of very good sensitivity but with less specificity. The authors discuss the critical indications and limitations of each investigation.
Aortic atheroma, involving the ascending aorta and proximal aortic arch, is associated with an increased risk of cerebral and peripheral embolic complications and cardiovascular complications (acute myocardial infarction, vascular death, peripheral arterial ischaemia). These data were established on prospective, case-control, anatomical studies, which all used transoesophageal echocardiography as the reference diagnostic method. In the absence of an alternative radiological imaging technique, transoesophageal echocardiography describes the thickness of the plaque, its luminal extension, its more or less regular nature, and the presence of plaque calcifications and sessile or mobile thrombi. Some predisposing factors are associated with the thromboembolic risk of aortic athero-sclerosis: elevated plasma fibrinogen, presence of circulating anticoagulants, elevated plasma homocysteine. The mana-gement of these patients is purely empirical at the present time. Antiplatelet treatment is formally indicated following cerebral infarction. The presence of thrombosis on the atherosclerotic plaque constitutes an indication for anticoagulant therapy. The indication for thrombolysis and surgical resection of the aortic atheroma is anecdotal, in the absence of proof of their efficacy on large series. Progress in radiological and echocardiographic imaging, and complementary epidemiological studies should be able to more clearly define patient subgroups at higher risk. Aortic atherothrombosis was also recently associated with increased cardiovascular complications in patients with atrial fibrillation (SPAF III trial).
BACKGROUND: Atherosclerotic disease of the aortic arch has been found to be associated with the risk of ischemic stroke. We have shown that atherosclerotic plaques > or = 4 mm in thickness in the ascending aorta and proximal arch detected by transesophageal echocardiography are a risk factor for ischemic stroke. The purpose of this study was to evaluate the impact, if any, of plaque morphology (ulceration, hypoechoic plaques or calcification) on the risk of subsequent vascular events. METHODS AND RESULTS: We followed for a period of 2 to 4 years, a cohort of 334 patients 60 years or older who were consecutively admitted with brain infarction and who had transesophageal echocardiography. The risk of vascular events in patients with plaques in the aortic arch according to the presence of surface ulceration, calcifications, and sessile or mobile thrombus was estimated during a total of 788 person-years of follow-up. Hypoechoic plaques, calcifications, and ulceration were more frequently found in patients with plaques > or = 4 mm as compared with those with plaques < 4 mm. The presence of ulceration did not increase the relative risk of vascular events in patients with plaque > or = 4 mm (the relative risk was 4.3 [P<.001] in those with ulceration and 5.7 [P<.001]) in those without ulceration. The lack of calcification did increase the risk of vascular events in patients with plaque > or = 4 mm. The highest relative risk of events was found among the patients with noncalcified plaques (relative risk, 10.3; 95% confidence interval, 4.2 to 25.2; P<.001). The risk of events was systematically higher in patients without calcifications than in patients with calcifications regardless of what other morphological features were considered. CONCLUSIONS: In patients with brain infarction, the risk associated with aortic plaque thickness (> or = 4 mm) is markedly increased by the absence of plaque calcifications. These findings are important for the design of therapeutic trials in such patients.
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BACKGROUND: Spontaneous cervical artery dissections are a relatively common cause of ischemic stroke in young adults. Their mechanism is unknown, though it is generally assumed that an underlying minor form of extracellular matrix defect could exist. The present study tested the hypothesis that aortic and cardiac morphological abnormalities usually seen in patients with heritable connective diseases are more frequent in patients with spontaneous cervical artery dissections than in patients without such dissections. METHODS AND RESULTS: We performed a case-control study of 28 case patients with spontaneous cervical artery dissection and 84 control subjects with an ischemic stroke not due to cervical artery dissection. Control subjects were matched to case patients for age (+/-5 years), sex, and year of hospitalization. The aortic root was more frequently enlarged (ie, diameter > 34 mm) in case patients (56%) than in control subjects (15%). Mitral valve prolapse, mitral valve dystrophy, and aortic valve dystrophy were more frequent in case patients than in control subjects. In multivariate analyses, aortic diameter > 34 mm was the only variable associated with an increased risk of spontaneous cervical artery dissection (odds ratio, 14.2; 95% CI, 3.2 to 63.6; P < .001). CONCLUSIONS: These results suggest that aortic root diameter enlargement is associated with an increased risk of spontaneous cervical artery dissection. This finding is consistent with the idea that a generalized defect of the extracellular matrix is present in patients with spontaneous cervical artery dissection.
Translational regulation plays a major role in plant gene expression. Recent advances have been made in understanding how this mechanism of control is directed in the chloroplast as well as in the cytoplasm. Our knowledge of translational regulation in plant mitochondria, however, is limited. Translational control of gene expression in yeast mitochondria suggests that similar mechanisms will also play a significant role in the expression of plant mitochondrial genes.
Arbutamine is a new catecholamine designed for use as a pharmacologic stress agent. This study compared the sensitivity of arbutamine with symptom-limited exercise to induce echocardiographic signs of ischemia. Arbutamine was administered by a computerized closed-loop delivery system that controls the infusion rate of arbutamine toward a predefined rate of heart rate increase and maximum heart rate limit. Beta blockers were stopped > or = 48 hours before both tests. Stress was stopped for intolerable symptoms, or clinical, electrocardiographic or echocardiographic signs of ischemia (new or worsening wall motion abnormality), target heart rate (> or = 85% age predicted maximum heart rate), or plateau of heart rate response. Thirty-seven patients were entered into the study (35 arbutamine and exercise, 1 arbutamine only, 1 exercise only), of which 30 had angiographic evidence of coronary artery disease (> or = 50% lumen diameter narrowing). Rate-pressure product increased significantly in response to both stress modalities (p < 0.001) and was significantly greater with exercise (11,308 +/- 2,443) than with arbutamine (9,486 +/- 2,479, p < 0.001). The time to maximum heart rate was longer during arbutamine stress echocardiography than during exercise testing (17.3 +/- 9.4 versus 9.3 +/- 4.2 minutes, respectively, p < 0.001). There were more patients with interpretable echo data for arbutamine (82%) than for exercise (67%). Sensitivity for recognition of myocardial ischemia was 94% (95% confidence interval 70% to 100%) and 88% (95% confidence interval 62% to 98%), respectively. The most frequent adverse events during arbutamine (n = 36) were dyspnea (5.6%) and tremor (5.6%). Two arbutamine stress tests were discontinued due to arrhythmias: 1 patient had premature atrial and ventricular beats, and the other had premature atrial contractions and atrial fibrillation. Arrhythmias were well tolerated and resolved without sequelae. In conclusion, the sensitivity of arbutamine to induce echocardiographic signs of ischemia was similar to that of exercise despite a lower rate-pressure product. Arbutamine was well tolerated and provides a reliable alternative to exercise echocardiography.
BACKGROUND: Although many patients now survive the short-term complications of bone marrow transplantation for life-threatening hematologic disease, information on the health and activity of long-term survivors is sparse. OBJECTIVE: To evaluate the morbidity and mortality of patients surviving more than 5 years after allogeneic bone marrow transplantation. DESIGN: Retrospective, multicenter study. PATIENTS: 798 recipients of bone marrow transplants (477 adults, 321 children) from 43 European centers. Patients had received transplants before December 1985 and had survived at least 5 years. Patients had received allogeneic or syngeneic bone marrow for leukemia, lymphoma, inborn diseases of the hematopoietic and immune systems, and severe aplastic anemia. MEASUREMENTS: Survival, clinical performance according to Karnofsky score (in increments of 10%), and social reintegration were assessed as outcomes. Patient age and sex, primary disease and status at transplantation, histocompatibility of the donor, conditioning regimen, type of prophylaxis of graft-versus-host disease, and acute and chronic graft-versus-host disease were evaluated as variables. RESULTS: For the 55 5-year survivors, actuarial mortality was 8% at 10 years and 14% at 15 years. The leading causes of death were disease recurrence (21 patients), chronic graft-versus-host disease with complicating infections and lung disease (11 patients), secondary cancer (8 patients), and the acquired immunodeficiency syndrome (AIDS) (5 patients). When patients with recurrent disease were excluded, late death was associated with chronic graft-versus-host disease (P < 0.001), occurrence of secondary cancer (P < 0.001), male sex of the patient (P = 0.05), and female sex of the donor (P = 0.002). Clinical performance was normal (Karnofsky score, 100%) or minimally reduced (Karnofsky score, 90%) in 93% of patients; 89% of patients resumed full-time work or school. Reduced performance status and incomplete resumption of social activity were associated with chronic graft-versus-host disease, recurrent leukemia, AIDS, secondary cancer, organ dysfunction, and neurologic or psychological problems. Other risk factors for incomplete resumption of social activity were female sex (P = 0.002) and older age at transplantation (P = 0.001). CONCLUSIONS: More than 5 years after bone marrow transplantation, most patients were in good health (93%) and had returned to full-time work or school (89%). Recurrence of the primary disease, secondary cancer, and chronic graft-versus-host disease and its sequelae remain problems for some patients.
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The pathophysiology and clinical severity of beta-thalassemia are related to the degree of alpha/non-alpha-chain imbalance. A triplicated alpha-globin gene locus can exacerbate effects of excess alpha-chains caused by a defective beta-globin gene, although this is not observed in all cases. Extensive studies on this condition are lacking. We report a group of 17 patients who are heterozygous for both the alpha alpha alpha(anti-3.7) allele and a mutation in the beta-globin gene cluster. Their clinical phenotypes varied: six had mild anemia with microcytosis and hypochromia, while 11 had more severe anemia with splenomegaly requiring splenectomy (three cases) and blood transfusions (four cases). Different phenotypes were also evident in the presence of the same beta-thalassemia mutation: in one family, two individuals had the same alpha- and beta-globin genotypes but presented with different hematologic phenotypes. In addition, the complex interaction involving a triplicated alpha-globin gene, beta39- and delta+27-thalassemia mutations is studied in a family with two siblings presenting with hemolytic anemia, normal Hb A2 and increased Hb F. Analysis of this series of patients suggests that additional genetic determinants play a role in modulating phenotypic expression in individuals with identical alpha- and beta-globin genotypes. Interaction with a triplicated alpha-gene can play a role in the clinical presentation of patients with defective beta-globin gene expression and should be considered in the diagnosis of atypical cases.
Pharmacokinetic (PK) parameters for terbinafine were assessed in 15 elderly and 15 young healthy subjects randomized to receive 250 mg Lamisil once daily for 15 d in a two-period, two-treatment, two-sequence, crossover (fed versus fasted) design within age groups. On each treatment day except days 8 and 15, subjects took Lamisil with food at 8:00 a.m. On days 8 and 15, subjects took the drug under either fed or fasting conditions according to treatment sequence, and 24 h PK profiles were obtained. Two analyses of the pharmacokinetic data were undertaken. In a noncompartmental analysis, AUC0-24h, Cmax, C0h, and tmax were computed for each subject on each of days 8 and 15, and the influences of food condition and age on these variables were assessed by analysis of variance. AUC0-24h and C0h were found to be larger (p < 0.5) among elderly subjects than young subjects on day 15, and tmax was prolonged (p < 0.05) under the fed condition on day 15. Similar trends on day 8, as well as generally higher exposures under the fed condition on both days, were not statistically significant. A three-compartment model fitted to the complete sequence of 33 terbinafine concentrations measured over 29 d for each subject separately permitted a within-subject assessment of the food effect that confirmed prolonged absorption and increased bioavailability (p < 0.05) under the fed condition. Across-subject comparisons of oral clearances estimated with the model also confirmed the increased exposures (lower clearances) among the elderly (p < 0.05). The drug was well tolerated in both age groups. In particular, greater drug exposure in the elderly did not result in greater toxicity, as indicated by the safety evaluations in the study.
Proteins play a pivotal role in thermophily. Comparing the molecular properties of homologous proteins from thermophilic and mesophilic bacteria is important for understanding the mechanisms of microbial adaptation to extreme environments. The thermophile Thermoanaerobacter (Thermoanaerobium) brockii and the mesophile Clostridium beijerinckii contain an NADP(H)-linked, zinc-containing secondary alcohol dehydrogenase (TBADH and CBADH) showing a similarly broad substrate range. The structural genes encoding the TBADH and the CBADH were cloned, sequenced, and highly expressed in Escherichia coli. The coding sequences of the TB adh and the CB adh genes are, respectively, 1056 and 1053 nucleotides long. The TB adh gene encoded an amino acid sequence identical to that of the purified TBADH. Alignment of the deduced amino acid sequences of the TB and CB adh genes showed a 76% identity and a 86% similarity, and the two genes had a similar preference for codons with A or T in the third position. Multiple sequence alignment of ADHs from different sources revealed that two (Cys-46 and His-67) of the three ligands for the catalytic Zn atom of the horse-liver ADH are preserved in TBADH and CBADH. Both the TBADH and CBADH were homotetramers. The substrate specificities and thermostabilities of the TBADH and CBADH expressed inE. coli were identical to those of the enzymes isolated from T. brockii and C. beijerinckii, respectively. A comparison of the amino acid composition of the two ADHs suggests that the presence of eight additional proline residues in TBADH than in CBADH and the exchange of hydrophilic and large hydrophobic residues in CBADH for the small hydrophobic amino acids Pro, Ala, and Val in TBADH might contribute to the higher thermostability of the T. brockii enzyme.
Most processing stages theorists assume that response selection processes are largely autonomous from earlier perceptual analysis of information. We report findings that challenge this assumption and suggest that a much more complex interaction exists between perception and action. Specifically our study demonstrates that the initial analysis of visual objects into features from different dimensions strongly constrains postperceptual processes of response selection. When a target that is associated with a response on the basis of one dimension is presented simultaneously with flankers that are associated with a response on the basis of another dimension, the response to the target is not affected by the identity of the flankers. These findings hold under a variety of conditions and appear to be specific to perceptual dimensions. When both target and flankers are associated with a response on the basis of the same dimension, the response to the target is affected by the identity of the flankers even when the target and flankers are perceptually dissimilar or belong to different semantic categories (digits and letters). We propose a model of response selection that can account for these findings. The model assumes that initial response selection processes for simple features are performed within dimensional modules and suggests a specific mediating role for spatial attention. We argue that this model is compatible with several other lines of research.
Brain-damaged patients with unilateral spatial neglect ignore aspects of the world located on the side opposite their lesion. In the present study we examined the performance of unilateral neglect patients (UN) on an SRT task in which a hybrid repeating sequence (21313) was used. We analyzed the patients' performance for each location separately as a function of the target's location in the trial preceding the response. The UN patients were severely limited in their learning of the sequence when compared to normal controls. In particular, they appeared to learn unique associations (21 and 13) but not ambiguous ones (31 and 32). We discuss two possible explanations for this phenomenon. The first is that UN patients show a deficit similar to that of normal subjects in dual task situations. The second is that the learning deficit is unique to spatial processing impairments of UN patients and is not directly related to research with normal population. We outline future research that may distinguish between these two explanations.
INTRODUCTION: Pelvic recurrence is a significant problem following curative resection for rectal cancer. Although treatment options include surgery, chemotherapy, radiotherapy, or any combination of these, the role of surgery remains controversial in management of these patients. PURPOSE: In this study, we have attempted to define the patient with pelvic recurrence following curative rectal surgery who may benefit from reresection. METHODS: A review of the prospective colorectal database at Memorial Sloan Kettering Cancer Center (MSKCC) between 1983 and 1991 identified 25 patients who had pelvic recurrence following a curative resection for rectal cancer and 52 patients who had their initial rectal surgery at an outside institution (OI) and their pelvic recurrence treated at MSKCC. Survival was calculated from time of recurrence by the Kaplan-Meier method, and survival comparisons were made by log-rank analysis. There were no differences between the two groups related to age, gender, type of initial surgery, stage, or use of adjuvant therapy. RESULTS: For the MSKCC group, median time to initial recurrence was 18 months, and median survival was 40 months. Recurrence was symptomatic in 17 patients and asymptomatic in 8 patients. Pain and bleeding accounted for more than one-half of symptomatic recurrences. Of the 17 symptomatic recurrences, 11 (65 percent) had relief of preoperative symptoms. There were no clinical or pathologic factors identified of the primary tumor or recurrence that predicted improved survival following salvage therapy. It was not possible to preoperatively determine which patients could undergo curative reresection. For the OI group, median time to recurrence was 13.7 months, and median survival from time of initial recurrence was 31 months. Curative reresection was the only factor that predicted for improved survival compared with noncurative treatment (P = 0.02). A comparison of the two groups revealed that pelvic recurrence was more likely to be reresected for cure in the OI group vs. the MSKCC group (34/51 vs. 9/25; P < 0.02). There was no survival difference between the two groups when comparing curative with noncurative management of these patients. CONCLUSIONS: Symptoms from recurrent rectal cancer can be palliated with surgery. The only patients who had a survival benefit were those patients in the OI group whose disease could be completely resected. These differences in reresection rates may be attributable to the presence or absence of available planes for dissection around the recurrence in the OI group, as determined by the method of initial curative resection.
UNLABELLED: Two hundred and fifteen children aged 4 months 6 years with acute otitis media (AOM) were randomized to be treated either by a single i.m. injection of ceftriaxone, 50 mg/kg, with a second dose in the event of unsatisfactory response after 48 h or a history of recurrent AOM (109 patients) or amoxicillin clavulanate 12.5 mg tid (106 patients). The failure rate was similar in children treated by ceftriaxone and amoxicillin clavulanate, 4.6% and 4.7%, respectively (standard error for intergroup difference -2.87%, 95% confidence interval -5.62% to 5.87%). No significant differences between the groups were found in the dynamics of the resolution of the acute symptomatology, otoscopy findings, relapse rate at 30 days or tympanographic evidence of middle ear effusion at the scheduled visits on days 30, 60 and 90. Recurrence of AOM between days 31 and 90 was observed significantly in more children treated with amoxicillin clavulanate than with ceftriaxone--25 out of 84 (29.4%) versus 11 out of 81 (13.6%) (P = 0.012). CONCLUSION: Ceftriaxone injection(s) is as efficient at least as 10-day oral amoxicillin clavulanate for treatment of acute otitis media in children. Although not recommended as routine, ceftriaxone can be considered in the management of acute otitis media under special circumstances, particularly in cases when the ability to tolerate or absorb oral drugs is compromised, in children refusing or unable to take oral therapy or when the compliance is questionable.