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Biomedical subjects

M Rosenthal

Publications and source records attributed to M Rosenthal.

At least 55 records · Page 3Linked to original sources

Multisite study of a second generation whole blood rapid assay for cardiac troponin T.

We evaluated a second generation, qualitative, whole blood rapid assay for cardiac troponin T (cTnT), which employs a more cardio-specific troponin T mouse monoclonal capture antibody. Using quantitative cTnT enzyme-linked immunosorbent assay (ELISA) results as the benchmark for accuracy, we compared the performance of the second generation and the original whole blood rapid assays in 445 samples from patients with the following diagnoses, determined by medical record review: myocardial infarction, coronary bypass surgery, ischaemic heart disease, musculoskeletal disease, renal failure or other noncardiac conditions. Overall, concordance between the second generation cTnT Rapid Assay and the quantitative cTnT ELISA, compared using the McNemar test and a cut-off concentration of 0.1 microgram/L, was in the range 76-94% for each patient group. Using a receiver operating characteristic plot, the cut-off for the second generation cTnT Rapid Assay was in the range 0.06-0.08 microgram/L. We conclude that the second generation cTnT whole blood assay has a 2.5-fold lower analytical cut-off than the original rapid assay (0.2 microgram/L) and may represent a more sensitive clinical tool for the rapid triage and risk stratification of cardiac patients.

Adolescent↗

The effects of surgically treated pulmonary stenosis on lung growth and cardiopulmonary function in children during rest and exercise.

The effects of high pulmonary blood flow and pressure on pulmonary development are well understood, but the effect of low pulmonary flow/pressure is not. Pulmonary stenosis (PS) was therefore used as a model to determine its effect on lung development, which was assessed noninvasively by carbon monoxide transfer at rest and during exercise. One hundred and six control children (55 males, 8-16 yrs) and 11 children with isolated valvar or subvalvar PS surgically corrected > or =10 yrs prior to the study without residual stenosis/regurgitation were evaluated. Measurements of effective pulmonary blood flow, stroke volume, arteriovenous oxygen difference (AVO), transfer factor and transfer constant, alveolar ventilation and anaerobic threshold were performed using a mass spectrometer. Data from the normal children allowed calculation of z-scores for the study group matched for age, sex, pubertal stage and surface area. PS children at rest had a significantly lower forced expired volume in one second, cardiac frequency and transfer constant with a raised oxygen consumption and AVO which persisted on exercise. During exercise, the cardiac frequency was 12 beats x min(-1) slower and AVO 0.017 L greater than controls (p<0.05). A persistently mildly raised effective functional residual capacity (0.2 L x m(-2)) during exercise led to a reduced transfer constant (0.35 mmol x min(-1) x kPa(-1) x L(-1)), although the percentage rise (28%) from rest to peak exercise was normal. The percentage fall in stroke volume from the penultimate exercise stage to peak exercise stage was greater in PS children (24%, 95% confidence interval 11-37) than control children (2.4, -2-10, p<0.005). In conclusion, although the effects are small, pulmonary stenosis does affect cardiopulmonary function after surgery. This needs to be considered when contemplating the timing of treatment.

Adolescent↗

Supportive telephone outreach as an interventional strategy for elderly patients in a period of crisis.

During the Gulf War in 1991 a telephone-based support system was established for elderly patients living at home in Israel. The study population involved 93 elderly patients (mean age 74), who had recently been discharged from hospital and were chosen for supervision by the Home-Care Unit of the Tel Aviv Sourasky Medical Center, Israel. Two different teams were involved with the telephone support calls: secretarial staff (nonprofessional team) and social workers (professional team). The research examined the characteristics of the study population and also included a comparison between the two groups of patients receiving the psycho-social support. The latter indicated that better results of outcome indices were achieved by the professional team. Further, this study demonstrated the feasibility of telephone-support outreach as an interventional strategy for psycho-social support for elderly patients at a time of crisis.

Aged↗

Quantitative trait loci for blood pressure exist near the IGF-1, the Liddle syndrome, the angiotensin II-receptor gene and the renin loci in man.

Blood pressure (BP) is heritable and finding quantitative trait loci that influence BP is an important step in identifying genes responsible for BP regulation. Sixty-six pairs of dizygotic (DZ) twin subjects and their parents were used in a sib-pair analysis to look for linkage of selected candidate genes to the quantitative trait BP. Microsatellite markers were tested in the vicinity of the gene loci for insulin-like growth factor-1 (IGF-1), Liddle syndrome, autosomal-dominant hypertension with brachydactyly, angiotensinogen, angiotensin II type 1 receptor, angiotensin-converting enzyme, renin, and lipoprotein lipase. BP was measured in a standardized manner. Heart size was determined echocardiographically. Significant linkage was found at the IGF-1, Liddle syndrome, and AT1 receptor gene for systolic BP. Linkage for diastolic BP was found at the autosomal-dominant hypertension with brachydactyly locus. Both systolic and diastolic BP were linked to the renin gene locus. The linkage was most consistent for the IGF-1 gene locus and systolic BP. Linkage was also found between the IGF-1 gene locus and posterior cardiac wall thickness, septal thickness, and left ventricular mass index. It is suggested that these quantitative trait loci may be important for the subsequent detection of allelic variants for elevated BP. Furthermore, these results linking the IGF-1 gene locus to both BP and cardiac dimensions underscore the importance of the IGF-1 gene as a candidate gene for cardiovascular disease.

Adult↗

Diogenes syndrome and hoarding in the elderly: case reports.

Presented here are two case reports of elderly persons with Diogenes syndrome (variously known as senile breakdown, social breakdown and senile squalor syndrome). Diogenes syndrome is often (but not always) characterized by a tendency to hoard excessively (syllogomania). The first patient was diagnosed as having both a schizotypal personality disorder and obessive-compulsive disorders (OCD) while the second was diagnosed as having a schizoid personality disorder. Only the former demonstrated the tendency to hoard rubbish. The Diogenes syndrome in both cases can be hypothesized to be a reaction to stress in elderly people with certain personality characteristics or as the end stage of a personality disorder. The hoarding behavior that was manifested only in the first case can probably be the result of the presence of an OCD. The authors raise the possibility that OCD may be the cause of hoarding rubbish in those cases of Diogenes syndrome in which hoarding exists and cannot be explained by psychotic disorders, dementia or any other mental disorders due to a general medical condition (GMC) or substance-related disorders.

Aged↗

Sertraline in children and adolescents with obsessive-compulsive disorder: a multicenter randomized controlled trial.

CONTEXT: The serotonin reuptake inhibitors are the treatment of choice for patients with obsessive-compulsive disorder; however, empirical support for this assertion has been weaker for children and adolescents than for adults. OBJECTIVE: To evaluate the safety and efficacy of the selective serotonin reuptake inhibitor sertraline hydrochloride in children and adolescents with obsessive-compulsive disorder. DESIGN: Randomized, double-blind, placebo-controlled trial. PATIENTS: One hundred eighty-seven patients: 107 children aged 6 to 12 years and 80 adolescents aged 13 to 17 years randomized to receive either sertraline (53 children, 39 adolescents) or placebo (54 children, 41 adolescents). SETTING: Twelve US academic and community clinics with experience conducting randomized controlled trials. INTERVENTION: Sertraline hydrochloride was titrated to a maximum of 200 mg/d during the first 4 weeks of double-blind therapy, after which patients continued to receive this dosage of medication for 8 more weeks. Control patients received placebo. MAIN OUTCOME MEASURES: The Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS), the National Institute of Mental Health Global Obsessive Compulsive Scale (NIMH GOCS), and the NIMH Clinical Global Impressions of Severity of Illness (CGI-S) and Improvement (CGI-I) rating scales. RESULTS: In intent-to-treat analyses, patients treated with sertraline showed significantly greater improvement than did placebo-treated patients on the CY-BOCS (adjusted mean, -6.8vs -3.4, respectively; P=.005), the NIMH GOCS (-2.2 vs -1.3, respectively; P=.02), and the CGI-I (2.7 vs 3.3, respectively; P=.002) scales. Significant differences in efficacy between sertraline and placebo emerged at week 3 and persisted for the duration of the study. Based on CGI-I ratings at end point, 42% of patients receiving sertraline and 26% of patients receiving placebo were very much or much improved. Neither age nor sex predicted response to treatment. The incidence of insomnia, nausea, agitation, and tremor were significantly greater in patients receiving sertraline; 12 (13%) of 92 sertraline-treated patients and 3 (3.2%) of 95 placebo-treated patients discontinued prematurely because of adverse medical events (P=.02). No clinically meaningful abnormalities were apparent on vital sign determinations, laboratory findings, or electrocardiographic measurements. CONCLUSION: Sertraline appears to be a safe and effective short-term treatment for children and adolescents with obsessive-compulsive disorder.

Adolescent↗

Long-term treatment effects of vitamin E for tardive dyskinesia.

BACKGROUND: Several studies have found that alpha-tocopherol (vitamin E) can effectively treat tardive dyskinesia (TD). A limitation of these trials is their short treatment durations (maximum of 12 weeks), which do not allow us to address the effects of long-term treatment. METHODS: To participate, patients had to have TD and be on stable oral medications. The study enrolled 40 patients who received up to 36 weeks of treatment with d-vitamin E (1600 IU per day) or placebo. RESULTS: Using the Abnormal Involuntary Movements Scale (AIMS) score (sum of items #1-7) to measure TD severity, the study found a significant difference (3 points) in mean AIMS scores, in favor of vitamin E, starting at 10 weeks of treatment and continuing through the full 36 weeks. We used linear mixed-effects regression to quantify the impact of several covariates, and found that treatment assignment. TD duration, and chlorpromazine equivalents had significant effects on decreasing the AIMS score. CONCLUSIONS: The study's finding that vitamin E is effective in treating TD agrees with results from prior studies and provides evidence that the effect may extend to treatment of up to 36 weeks. These findings are in direct contrast to those of VA Cooperative Study #394, a much larger, long-term, multi-site study, conducted by many of the same investigators, in which Vitamin E was not superior to placebo.

Antioxidants↗

The value of ultrafast computed tomography in the investigation of pediatric chest disease.

Ultrafast computed tomography (CT) can be performed in almost all children with little or no sedation. The benefit has to be balanced against financial cost and radiation dose. Since observing a steady increase in numbers of scans performed, we analyzed the contribution to management of 106 pediatric chest CT scans performed over a 12-month period. Forty-eight of 106 yielded a positive diagnosis and a further 43/106 provided clearly useful information. CT was most useful in children with chronic productive cough (21/48 scans showed bronchiectasis) and suspected interstitial lung disease. It was least useful in the preoperative assessment of empyema complicating community-acquired pneumonia (0/11 scans giving information that changed management). We conclude that the increased ease of performance of chest CT in children has not led to a large number of inappropriate requests. In the large majority of cases, diagnostically useful information was provided.

Adolescent↗

A positive effect of p21cip1/waf1 in the colony formation from murine myeloid progenitor cells as assessed by retroviral-mediated gene transfer.

p21cip1/waf1 is a cyclin dependent kinase inhibitor. We have previously reported stimulation of p21cip1/waf1 by steel factor and GM-CSF in a factor dependent cell line and of p21cip1/waf1 involvement in hematopoiesis in vivo in p21cip1/waf1 gene knockout (-/-) mice. To further assess a role for increased p21cip1/waf1 in hematopoietic progenitor cells, we developed the retroviral vector L(p21cip1)SN to transcriptionally regulate p21cip1/waf1 from the Mo-MLV LTR. L(p21cip1)SN and the control vector LXSN were used to transduce murine bone marrow progenitor cells from p21cip1/waf1 (-/-) and littermate control (+/+) mice, as well as from other mouse strains. Hematopoietic colony formation by transduced cells was assessed in semi-solid culture medium with multiple growth factors. Myeloid colony formation by bone marrow cells from p21cip1/waf1 (-/-) mice was significantly lower than that by (+/+) mouse cells. Transduction of cells with LXSN had no effect on colony formation: however, (-/-) cells transduced with L(p21cip1)SN formed significantly greater numbers of colonies than either LXSN-transduced (-/-) or (+/-) cells. Moreover, L(p21cip1)SN-transduced (+/+) cells formed significantly more colonies than LXSN-transduced (+/+) cells. Increased cloning efficiency of progenitors from normal strains of mice induced by L(p21cip1)SN compared to LXSN-transduced cells was seen whether unseparated or highly purified populations of Sca1+ Lin- marrow cells were used. Gene transfer of L(p21cip1)SN increased the size and number of cells per colony, as well as the number of colonies compared to LXSN gene transfer. No colonies grew from non-transduced, LXSN-, or L(p21cip1)SN-transduced cells when no growth factors were added to the cultures. These results document the positive effect of p21cip1/waf1 in the proliferation and/or differentiation of the murine myeloid progenitor cells that lead to colony formation.

Animals↗

Depression following traumatic brain injury.

OBJECTIVE: Review the existing literature on the incidence, neurobiological and psychosocial correlates, and methods of assessment and treatment of depression following traumatic brain injury (TBI). DATA SOURCES: Computerized database searches of the English-language literature from Index Medicus, Psychological Abstracts, Excerpta Medica, and Cumulative Index of Nursing and Allied Health Literature. STUDY SELECTION: Given the relatively small number of publications specifically related to TBI and depression, all studies appearing in the peer-reviewed literature were included in the review. In addition, studies examining depression and other neurologic diseases (eg, stroke) were also reviewed as to the potential applicability of the theoretical model or methodology used. CONCLUSIONS: Depression occurs with sufficient frequency to be considered a significant consequence after TBI. Depression can impede the achievement of optimal functional outcome, whether in the acute or chronic stages of recovery. It appears that a combination of neuroanatomic, neurochemical, and psychosocial factors is responsible for the onset and maintenance of depression. Its treatment is typically psychopharmacologic, with best results obtained from nontricyclic antidepressants. These results have not been confirmed in double-blind clinical trials, however. Future research should use comprehensive, integrative models of depression that include demographic, biologic, and psychosocial factors; enhanced functional neuroimaging techniques; controlled studies of psychopharmacologic and other interventions; and prospective designs with long-term follow-up.

Antidepressive Agents↗

Oxygen sensitivity of mitochondrial redox status and evoked potential recovery early during reperfusion in post-ischemic rat brain.

Inspired oxygen (FiO2) was manipulated during the early reperfusion period after global cerebral ischemia (four-vessel occlusion of 20 or 30 min duration) in anesthetized rats. The goal was to determine whether oxygen availability during the early reperfusion period alters recovery of mitochondrial redox state and evoked electrical activity. The effectiveness of post-ischemic oxygen treatment was monitored at the tissue level with oxygen sensitive microelectrodes, and at the mitochondrial level by reflection spectrophotometry of the redox state of cytochrome oxidase. Transiently decreasing FiO2 from 0.3 to 0.15 limited reperfusion-induced hyperoxygenation and post-ischemic mitochondrial hyperoxidation (PIMHo). Evoked potential recovery was improved by this treatment after 20 min ischemia but not after 30 min ischemia. Increasing FiO2 from 0.3 to 1.0 exacerbated PIMHo and tissue hyperoxygenation. Transient elevation of tissue oxygen tension after 30 min of global ischemia inhibited recovery of evoked potentials. These data suggest that a period of heightened vulnerability to oxidative stress occurs within the first 10 min of reperfusion after global ischemia. This period is characterized by tissue hyperoxygenation and mitochondrial hyperoxidation. Limiting oxygen availability during this period may improve the outcome while conversely elevating oxygenation may be detrimental.

Animals↗

Influence of a randomized clinical trial on practice by participating investigators: lessons from the Coronary Angioplasty Versus Excisional Atherectomy Trial (CAVEAT). CAVEAT I and II Investigators.

OBJECTIVES: We sought to determine whether the results of the first Coronary Angioplasty Versus Excisional Atherectomy Trial (CAVEAT-I) influenced subsequent practice patterns among the investigators. BACKGROUND: CAVEAT-I demonstrated that directional coronary atherectomy (DCA) resulted in higher rates of early complications at a higher cost and with no clinical benefit. We sought to determine whether these results influenced subsequent use of procedures among CAVEAT-I investigators. METHODS: We compared the results of a week-long registry of all coronary interventions performed at 35 CAVEAT-I sites in 1994 with those of a similar registry obtained in 1992 before the trial, the results of which were published in 1993. For control purposes, the use of procedures was studied at 24 additional sites to provide insight into practice at hospitals not participating in the trial. A total of 1,465 interventions were analyzed. RESULTS: Ninety-four percent of CAVEAT-I sites responded. Utilization rates differed between CAVEAT-I and CAVEAT-I follow-up (p < 0.001). Balloon angioplasty decreased from 83.8% to 68.5%, DCA increased slightly from 10.7% to 14.1%, and the use of other devices increased from 5.4% to 17.5%. Stand-alone balloon use was more prevalent at nonparticipating control sites than at sites that took part in CAVEAT-I (p < 0.001). CONCLUSIONS: Paradoxically, despite the negative findings of CAVEAT-I, there was a noteworthy trend toward an increase in the use of DCA and other devices at CAVEAT-I sites. Our findings suggest that among investigators in the trial, there may have been a lack of influence of trial data on clinical practice patterns 1 year after publication of the results. Ethics of protocol: Both CAVEAT I and II were approved by the Institutional Review Board at each study site.

Adult↗

Pulmonary response of normal human subjects to inhaled vasodilator substances.

1. Inhaled vasodilators such as nitric oxide and epoprostenol (prostaglandin I2) are now widely employed as supportive therapies to improve oxygenation and reduce pulmonary vascular resistance in patients with acute and chronic pulmonary hypertension. However, few data exist concerning their effects in normal individuals. The aim of this study was to characterize the response of the pulmonary circulation in normal individuals to inhaled nitric oxide and nebulized prostaglandin I2.2.Eight healthy volunteers were exposed to inhaled nitric oxide (0, 20 and 40 p.p.m.) and nebulized prostaglandin I2 (10 microgram/ml). Changes in effective pulmonary blood flow and diffusing capacity of the lung for carbon monoxide (TLCO) were measured using respiratory mass spectrometry. Bicycle ergometry was used to increase effective pulmonary blood flow as a positive control.3. Exercise produced significant increases in both effective pulmonary blood flow and TLCO, but neither nitric oxide nor prostaglandin I2 produced significant changes in either parameter.4.No significant change in pulmonary haemodynamics was demonstrated in response to inhaled nitric oxide or nebulized prostaglandin I2, using doses known to be effective in patients with acute and chronic pulmonary hypertension. These data suggest that the normal pulmonary vascular bed is not amenable to vasodilatation by inhaled drugs. The study further suggests that the normal pulmonary vasodilatation seen on exercise is not mediated pharmacologically, but is a secondary consequence to the mechanical effects of a rise in pulmonary blood flow. This study thus supports the view that there is no resting vasoconstrictor tone in the pulmonary vascular bed.

Administration, Inhalation↗

The value of classifying interstitial pneumonitis in childhood according to defined histological patterns.

AIMS: Interstitial pneumonitis in children is very rare and most cases have been classified according to their counterparts in adults, although the term 'chronic pneumonitis of infancy' has recently been proposed for a particular pattern of interstitial lung disease in infants. We reviewed our paediatric cases of interstitial pneumonitis, first, to look at the spectrum of histological patterns found in this age group and, second, to determine whether the classification of such cases in childhood is both appropriate and worthwhile. METHODS AND RESULTS: Twenty-five of 38 open lung biopsies showed an overlapping spectrum of interstitial pneumonitis, including three cases that fulfilled the histological criteria for chronic pneumonitis of infancy. There were 11 cases of reactive pulmonary lymphoid hyperplasia (either lymphoid interstitial pneumonitis or follicular bronchiolitis), five of which were associated with abnormalities of the immune system. Four cases were classified as desquamative interstitial pneumonitis and the remaining seven cases were classified as nonspecific interstitial pneumonitis. There were no cases with the histological features of usual interstitial pneumonitis. Most patients responded to steroids but tended to have a residual deficit in lung function. Mortality appeared to be associated with presentation at a young age. CONCLUSION: Classification of interstitial pneumonitis according to their adult counterparts is appropriate for this younger age group and can provide valuable information for the clinician. The term 'chronic pneumonitis of infancy' refers to a specific histological pattern, but whether it represents a separate disease or a reflection of pulmonary immaturity remains to be proven.

Adolescent↗

Community-based training after acquired brain injury: preliminary findings.

Persons entering or returning to the workforce after brain injury often require assistance to identify, locate, secure and maintain employment. This is especially true for workers from economically disadvantaged environments who may have limited pre-injury work experience. Supported employment, the use of natural supports, and community-based approaches are helpful for the process of identifying, securing and maintaining work. However, reports are limited as to how these approaches are helpful for economically disadvantaged persons, especially in identifying meaningful work. An approach is described here which combines work adjustment training and supported employment; which is helpful in identifying consumer interest, and in improving position attainment, job retention and work satisfaction. A sample of persons (n = 38) with brain injury were contacted after completing the programme. A total of 59% of these persons remained employed at follow-up, compared to 32% at time of injury. Additional outcome data are presented to describe the usefulness of this approach.

Adult↗