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Biomedical subjects

D J Cohen

Publications and source records attributed to D J Cohen.

At least 19 recordsLinked to original sources
PubMed1995

In-hospital and one-year economic outcomes after coronary stenting or balloon angioplasty. Results from a randomized clinical trial. Stent Restenosis Study Investigators.

BACKGROUND: Coronary stenting has been shown to improve initial success, reduce angiographic restenosis, and reduce the need for repeat revascularization compared with conventional balloon angioplasty (PTCA). Although previous studies have demonstrated that initial hospital costs for stenting are considerably higher than those for conventional PTCA, the impact of coronary stenting on long-term medical care costs remains unknown. METHODS AND RESULTS: Between January 1991 and June 1993, 207 consecutive patients with symptomatic coronary disease requiring revascularization of a single coronary lesion were randomized to receive initial treatment by either PTCA (n = 105) or Palmaz-Schatz coronary stent implantation (n = 102) in the multicenter STRESS trial. Detailed resource utilization and cost data were collected for each patient's initial hospitalization and for any subsequent hospital visits for 1 year after randomization. Compared with conventional angioplasty, coronary stenting resulted in additional catheterization laboratory costs, increased vascular complications, and longer length of stay. Initial hospital costs were thus approximately $2200 higher for stenting than for PTCA ($9738 +/- 3248 versus $7505 +/- 5015; P < .001). Over the first year of follow-up, however, patients assigned to initial stenting were less likely to require rehospitalization for a cardiac condition and underwent fewer subsequent revascularization procedures. Follow-up medical care costs thus tended to be lower for stenting than for conventional angioplasty ($1918 +/- 4841 versus $3359 +/- 7100, P = .21). Nonetheless, cumulative 1-year medical care costs remained higher for patients undergoing initial stenting ($11,656 +/- 5674 versus $10,865 +/- 9073, P < .001). Even after adjustment for the higher incidence of vascular complications in the stent group, total 1-year costs were $300 higher for stenting than for balloon angioplasty. CONCLUSIONS: Elective coronary stenting, as performed in the randomized STRESS trial, increased total 1-year medical care costs by approximately $800 per patient compared with conventional angioplasty. Future studies will be necessary to determine whether ongoing refinements in stent design, implantation techniques, and anticoagulation regimens can narrow this cost difference further by reducing stent-related vascular complications or length of stay.

Aged↗
PubMed1995

Psychosocial therapies for children and adolescents: overview and future directions.

The assessment and psychosocial treatment of children must consider developmental phase and stage, developmental tasks, the nature of the disorder (does it affect a narrow sector or one developmental line or is there a broad disruption of development?) and biological contributions (including constitution, maturational rate, and factors such as the onset of puberty). Treatments can be distinguished along dimensions, including theoretical emphases, degrees of definition of the treatment, scope, the "patient" (child, family), duration, frequency of contacts, combination with other modalities, etc. Similarly, choice of treatment is based on many factors, including the clinician's expertise, availability of resources, wishes of parents, cost, etc. Future research should be grounded in a theory of child development as well as a theory of therapeutic action. Treatments should be well defined and currently practiced, provided by experts, and arise from realistic situations. The study of therapies bridges basic and applied research and provides data of profound relevance for theories of child development.

Adolescent↗
PubMed1995

Plasma androgens in autism.

Plasma levels of testosterone and the adrenal androgen dehydroepiandrosterone sulfate (DHEA-S) were measured in male autistic subjects (31 prepubertal, 8 postpubertal), mentally retarded/cognitively impaired subjects (MR, 12 prepubertal), and normal control subjects (NC, 10 prepubertal, 11 postpubertal). Mean levels of plasma testosterone were similar in the postpubertal autistic (4.54 +/- 1.12 ng/ml) and postpubertal NC (5.02 +/- 1.87 ng/ml) groups. Plasma DHEA-S levels in postpubertal autistic (2170 +/- 1020 ng/ml) and postpubertal NC (1850 +/- 777 ng/ml) groups also were not significantly different. Similarly, no significant group differences were seen for testosterone or DHEA-S in the prepubertal autistic, MR, or NC individuals, although prepubertal MR individuals with cerebral palsy did have increased plasma DHEA-S levels compared to age-matched MR or NC individuals. Significant negative correlations were found between testosterone and whole blood serotonin (5-HT) levels in the combined (all subjects, all ages) groups and in the autistic group, suggesting that the effect of puberty on whole blood 5-HT may deserve further study. Data indicate that altered secretion of the androgens is not a common feature of autism. However, abnormalities of adrenal androgen secretion may be present in individuals with cerebral palsy.

Adolescent↗
PubMed1995

Acute and chronic effects of fluoxetine and haloperidol on mouse brain serotonin and norepinephrine turnover.

Evidence from clinical studies suggests that the noradrenergic system may play a role in the pathophysiology of antidepressant- and neuroleptic-induced akathisia. In limited previous neurochemical research, acute treatment with selective serotonin reuptake inhibitors (SSRIs) has been reported to increase rat brain norepinephrine (NE) turnover or release. We have examined the neurochemical effects of 2 hr, 4 day, and 20 day treatment with the SSRI fluoxetine, and the neuroleptic haloperidol, on regional brain monoamine metabolism. Short and long-term fluoxetine treatment produced substantial decreases (to 65-79% of control) in serotonin (5HT) turnover. However no effects of fluoxetine on mouse brain NE turnover--as assessed by forebrain, hypothalamus, and hindbrain 3-methoxy-4-hydroxyphenylglycol (MHPG) levels or MHPG/NE ratios--were observed. Acute (2 hr) fluoxetine also did not alter regional NE turnover in rat brain. In contrast, haloperidol tended to increase MHPG levels and MHPG/NE ratios in the mouse brain regions studied. The persistence of decreased 5HT turnover during fluoxetine treatment, the lack of an effect of fluoxetine on NE turnover, and the increased NE turnover seen after haloperidol may have important implications regarding drug responsivity and the mechanism of akathisia induction.

Animals↗
PubMed1995

Progressive renal insufficiency following cardiac transplantation: cyclosporine, lipids, and hypertension.

The increasing success of cardiac transplantation has been attributed to the availability of potent immunosuppressive agents, including cyclosporine. With improved graft and patient survival, the incidence of chronic renal insufficiency has increased. We reviewed the medical records of patients who had undergone orthotopic cardiac transplantation and had been followed for at least 3 years posttransplantation to determine the risk factors at initial evaluation and in the early posttransplantation period for subsequent renal insufficiency. We followed 80 adult patients over a mean period of 4.7 years: 39 patients had a serum creatinine > or = 2.4 mg/dL at last follow-up (renal insufficiency or RI group); 41 patients had a serum creatinine < or = 1.7 mg/dL at last follow-up (controls). RI patients tended to be older and had a lower mean glomerular filtration rate (GFR) at initial evaluation. There were no differences in race, gender, or previous history of hypertension between the two groups. Although both groups experienced an improvement in GFR at transplantation and a subsequent decline in GFR by 6 months posttransplantation, the RI group achieved a lower peak GFR at transplantation and a far lower mean GFR at the 6-month analysis. Only the RI group showed a continued decline in GFR. The RI group had more severe hypertension and required a significantly greater number of antihypertensive medications. The RI group had a higher mean total cholesterol at 6 months, but this difference was not sustained. They also had higher triglyceride levels and lower high-density lipoprotein (HDL) levels; there was no difference in low-density lipoprotein (LDL) levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Ethical issues in biological psychiatric research with children and adolescents.

OBJECTIVE: This article reviews, discusses, and elaborates considerations and recommendations summarized by the biological research working group at the May 1993 NIMH conference on ethical issues in mental health research on children and adolescents. METHOD: Notes from the conference were summarized and supplemented by a computer search of relevant literature. Drafts were circulated for comment to national and international experts, some of whom joined as coauthors. RESULTS: Issues addressed include possible overprotection by policy makers and institutional review boards arising out of the recognition of children's special vulnerability without equal recognition of their need for research; the definition of minimal risk, which has often been equated with no risk in the case of children; assessment of the risk-benefit ratio; procedures for minimization of risk, such as improved technology, "piggybacking" onto clinical tests, and age-appropriate preparation; the difficulty of justifying risk for normal controls; age-graded consent; special considerations about neuroimaging; "coercive" inducement, both material and psychological; disposition of unexpected or unwanted knowledge about individuals, including the subject's right not to know and parent's right not to tell; and socioeconomic status and cultural/ethnic equity. CONCLUSIONS: The working group adopted a position of advocacy for children's right to research access while recognizing that this advocacy must be tempered by thoughtful protections for child and adolescent subjects.

Adolescent↗
PubMed1995

Guanfacine treatment of comorbid attention-deficit hyperactivity disorder and Tourette's syndrome: preliminary clinical experience.

OBJECTIVE: Many children with Tourette's syndrome (TS) are handicapped more by difficulties with inattention, impulsivity, and hyperactivity than by their tics. However, stimulant medications used to treat attention-deficit hyperactivity disorder (ADHD) can exacerbate tics. Guanfacine is an alpha 2-adrenergic agonist that may have beneficial effects on attention, without the hypotensive or sedative effects of clonidine, which is often used as an alternative to stimulants. METHOD: An open-label study of guanfacine was performed in 10 children with TS+ADHD, aged 8 to 16 years. The duration of follow-up was 4 to 20 weeks, and the majority of subjects were treated with 1.5 mg/day. Ratings of tic severity and ADHD symptoms were obtained using the Yale Global Tic Severity Scale (YGTSS), the Tic Symptom Self Report (TSSR), and the Conners Parent Rating Scale. In addition, blind Continuous Performance Tests (CPTs) were performed at baseline and at two follow-up intervals in eight subjects. RESULTS: Guanfacine was associated with significant decreases in both commission errors (p < .02) and omission errors (p < .01) on the CPT. In addition, guanfacine caused a significant decrease in severity of motor (p < .02) and phonic (p < .02) tics as measured by the TSSR and the YGTSS, respectively. The most common side effects were transient sedation and headaches. CONCLUSION: Guanfacine may provide a safe alternative therapy for children with ADHD in the presence of tics. Future double-blind, controlled trials should be undertaken.

Adolescent↗
PubMed1995

An epidemiological study of trichotillomania in Israeli adolescents.

OBJECTIVE: To determine the prevalence of trichotillomania and comorbid psychopathology in nonreferred adolescents. METHOD: Using a questionnaire and interview, 794 Israeli 17-year-olds were screened for current and past hair-pulling and comorbid psychopathology. RESULTS: Eight current or past hair-pullers (5 male, 3 female) were identified, yielding a lifetime prevalence of hair-pulling of 1%. Four subjects reported current hair-pulling (point prevalence of 0.5%). None of these reported alopecia, distress, or tension before pulling; only two reported relief after pulling. Thus, none met the full DSM-III-R criteria for trichotillomania. Four subjects reported past but not current hair-pulling, with bald spots in two cases. Three of the four current hair-pullers had significant obsessive-compulsive symptoms, a significantly elevated rate compared to the entire screened population. Two subjects with obsessive-compulsive disorder also had generalized anxiety disorder and, in one case, chronic simple vocal tics. Hair-pullers did not differ significantly from non-hair-pullers in IQ, physical fitness, and overall competency, or prevalence of other comorbid disorders. CONCLUSIONS: In a community adolescent sample, only 25% of hair-pullers reported resulting bare spots and none endorsed both rising tension and subsequent relief. The prevalence of obsessive-compulsive symptoms was significantly elevated in these nonreferred hair-pullers.

Adolescent↗
PubMed1995

A case-controlled study of repetitive thoughts and behavior in adults with autistic disorder and obsessive-compulsive disorder.

OBJECTIVE: The purpose of this study was to investigate the types of repetitive thoughts and behavior demonstrated by adults with autistic disorder and compare them with those of age- and sex-matched adults with obsessive-compulsive disorder. METHOD: Fifty consecutive patients admitted to the Yale Adult Pervasive Developmental Disorders (Autism) Clinic with a primary diagnosis of autistic disorder (DSM-III-R and DSM-IV) completed the symptom checklist of the Yale-Brown Obsessive Compulsive Scale. Types of current obsessions and compulsions were evaluated. The comparison group consisted of 50 age- and sex-matched adults with obsessive-compulsive disorder (without tics) (DSM-III-R and DSM-IV). RESULTS: Direct discriminant function analysis showed that the patients with autistic disorder could be distinguished from those with obsessive-compulsive disorder on the basis of the types of current repetitive thoughts and behavior that they demonstrated. Compared to the obsessive-compulsive group, the autistic patients were significantly less likely to experience thoughts with aggressive, contamination, sexual, religious, symmetry, and somatic content. Repetitive ordering; hoarding; telling or asking (trend); touching, tapping, or rubbing; and self-damaging or self-mutilating behavior occurred significantly more frequently in the autistic patients, whereas cleaning, checking, and counting behavior was less common in the autistic group than in the patients with obsessive-compulsive disorder. In addition, a specific subset of seven obsessive-compulsive variables from the Yale-Brown Obsessive Compulsive Scale symptom checklist was identified that reliably predicted membership in the autistic group. CONCLUSIONS: These results suggest that the repetitive thoughts and behavior characteristics of autism differ significantly from the obsessive-compulsive symptoms displayed by patients with obsessive-compulsive disorder. Future studies are warranted to assess the treatment response and neurobiological underpinnings of repetitive thoughts and behavior in patients with autism and obsessive-compulsive disorder.

Adolescent↗
PubMed1995

Regulation of macrophage growth responses to colony-stimulating factor-1 by 1,25-dihydroxyvitamin D3.

1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) has previously been shown to affect the biology of a variety of immune cells, including the functions of macrophages. The effect of the vitamin D metabolite on the proliferative responses of macrophages to the cytokine colony-stimulating factor-1 (CSF-1) has been studied. It was found that this substance was able to suppress the growth responses of macrophages to CSF-1 as assessed by macrophage-tritiated thymidine uptake and also by cell counts. The effect was specific to this vitamin D metabolite because another vitamin D analogue, 25 hydroxyvitamin D3, did not have a similar effect on the responses of such cells to CSF-1. The results yield information on the regulatory role of 1,25(OH)2D3 on macrophage growth. It would appear that this vitamin D metabolite may act as a negative autoregulatory cytokine because it is produced by the macrophage when it is activated. A schema can be envisaged where CSF-1 is delivered to the macrophage to activate it and to cause it to proliferate. In the process, it also secretes 1,25(OH)2D3, which exerts a suppressive action to dampen this response.

Animals↗
PubMed1994

Abnormal magnetic resonance imaging T2 relaxation time asymmetries in Tourette's syndrome.

Recent imaging studies in Tourette's syndrome (TS) have reported a loss of normal asymmetry in basal ganglia volumes. Our recent report of reduced midline sagittal cross-sectional area in TS suggests that altered lateralization may be widespread throughout the TS cerebrum. We report here our analyses of cerebral asymmetries of T2 (transverse or spin-spin) relaxation times derived from multi-echo/multi-planar/spin-echo magnetic resonance images in 14 adult TS subjects and 14 matched normal control subjects. T2 relaxation times were found to be asymmetric throughout the cerebrum of normal control subjects, with differences seen between T2 times of corresponding regions of both cerebral hemispheres that were small in magnitude (2-5%) but of a high degree of statistical significance in all regions examined. Our hypothesis of altered T2 relaxation time asymmetries in TS was confirmed in a multivariate analysis of variance, with post hoc analyses suggesting that group differences were attributable to specific asymmetry differences in the TS insular cortex and frontal white matter. Exploratory analyses revealed group differences in T2 times of the amygdala and red nucleus, as well as significantly lower ferritin levels in the TS group. These findings are discussed in relation to the previous TS volumetric studies, and the tissue characteristics that might produce normal and abnormal relaxation time asymmetries are considered.

Adolescent↗
PubMed1994

Influence of oral felodipine on serum cyclosporine concentrations.

Hypertension and nephrotoxicity are frequent in renal transplant patients treated with cyclosporine. Calcium-channel blockers, because of their vasodilatory effects on the renal afferent arteriole, may be the anti-hypertensive agents of choice in this population. Unfortunately, many calcium channel blockers inhibit the clearance of cyclosporine, resulting in elevated blood levels, and worsening nephrotoxicity. Thirteen hypertensive renal transplant patients, on stable cyclosporine doses and with stable cyclosporine blood levels, had felodipine added to their antihypertensive regimens. The effect on cyclosporine level was measured. Mean trough serum cyclosporine concentration increased slightly, from 122.8 +/- 51.8 ng/ml to 143.1 +/- 81.9 ng/ml with chronic felodipine administration (p = NS). Mean systolic and diastolic pressures both fell significantly, by approximately 10 mmHg (systolic from 161 +/- 14 to 152 +/- 13 mmHg; diastolic from 100 +/- 6 to 90 +/- 7 mmHg). Serum creatinine remained unchanged. Four patients eventually discontinued felodipine. There was no significant change in their mean trough serum cyclosporine concentration when felodipine was discontinued. Thus, felodipine is an effective anti-hypertensive medication in cyclosporine-treated renal transplant recipients, without significant effect on cyclosporine blood levels, or adverse effect on allograft function.

Administration, Oral↗
PubMed1992

Predictors of long-term outcome after percutaneous balloon mitral valvuloplasty.

BACKGROUND: Percutaneous balloon mitral valvuloplasty is known to produce short-term hemodynamic and symptomatic improvement in many patients with mitral stenosis. Comprehensive assessment of the clinical usefulness of balloon valvuloplasty requires evaluation of patients' long-term outcomes. METHODS: We performed balloon mitral valvuloplasty in 146 patients between October 1, 1985, and October 1, 1991. Base-line demographic, clinical, echocardiographic, and hemodynamic variables were evaluated in order to identify predictors of long-term event-free survival. RESULTS: Balloon mitral valvuloplasty was completed successfully in 136 (93 percent) of the patients in whom the procedure was attempted; it resulted in an increase in the mean (+/- SD) mitral-valve area from 1.0 +/- 0.4 to 2.1 +/- 0.9 cm2 and a decrease in the mean transmitral pressure gradient from 14 +/- 5 to 6 +/- 3 mm Hg (P < 0.001 for both comparisons). The estimated overall five-year survival rate was 76 +/- 5 percent, and the estimated five-year event-free survival rate (the percentage of patients without mitral-valve replacement, repeat valvuloplasty, or death from cardiac causes) was 51 +/- 6 percent. According to multivariate Cox proportional-hazards analysis, the independent predictors of longer event-free survival were a lower mitral-valve echocardiographic score (a measure of mitral-valve deformity; range, 0 for a normal valve to 16 for a seriously deformed valve; P < 0.001), lower left ventricular end-diastolic pressure (P = 0.001), and a lower New York Heart Association (NYHA) functional class (P = 0.04). Patients with no risk factors for early restenosis or only one risk factor (echocardiographic score > 8, left ventricular end-diastolic pressure > 10 mm Hg, or NYHA functional class IV) had a predicted five-year event-free survival rate of 60 to 84 percent, whereas patients with two or three risk factors had a predicted five-year event-free survival rate of only 13 to 41 percent. CONCLUSIONS: Balloon mitral valvuloplasty as a treatment for selected patients with mitral stenosis has good long-term results. The long-term outcome after this procedure can be predicted on the basis of patients' base-line characteristics.

Catheterization↗