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Biomedical subjects

J A Cohen

Publications and source records attributed to J A Cohen.

At least 19 recordsLinked to original sources
PubMed2001

Treatment practices for childhood posttraumatic stress disorder.

OBJECTIVE: This study surveyed practices in treating childhood PTSD among child psychiatrists and non-M.D. therapists with self-identified interest in treating traumatized children. METHOD: An anonymous survey was mailed to 207 child psychiatrists ("medical") and 460 nonphysician ("non-medical") therapists inquiring about current interventions used to treat children with PTSD. RESULTS: Two hundred and forty-seven responses were received: of 77 medical and 82 nonmedical respondents who currently treat children with PTSD, a wide variety of modalities are used. Most preferred modalities among medical responders were pharmacotherapy, psychodynamic, and cognitive-behavioral therapy. Most preferred modalities among nonmedical respondents were cognitive-behavioral, family, and nondirective play therapy. Ninety-five percent of medical respondents used pharmacotherapy for this disorder; most preferred medications to treat childhood PTSD were selective serotonin reuptake inhibitors and alpha-adrenergic agonists. Several significant differences between medical and nonmedical practices were identified. CONCLUSIONS: There is little clinical consensus regarding the effectiveness of the many modalities used to treat traumatized children who have PTSD symptoms; empirical research is particularly needed to evaluate the efficacy of pharmacotherapy and EMDR.

Adult↗
PubMed2001

Multiple sclerosis: the importance of early recognition and treatment.

Primary practitioners need to know how to expedite the diagnosis and treatment of multiple sclerosis (MS), because treatments that can slow its course appear to be most effective when started early. Several lines of evidence demonstrate that tissue damage occurs very early in the disease, and much of this damage is clinically silent.

Adjuvants, Immunologic↗
PubMed2001

Aberrant expression of cell-cycle regulatory proteins in human mesenchymal neoplasia.

We previously demonstrated that approximately one-half of soft-tissue sarcomas were devoid of either pRB, the product of the retinoblastoma gene, or 16, the product of the MTS1/CDKN2 gene, while a smaller subset of aggressive mesenchymal tumors without metastatic potential did not express RB by immunohistochemistry. We now studied the expression of two additional important cell-cycle regulators, namely cyclin D1 and p53, in the same cohort of high- and low-grade lesions. In the aggregate, our data provide a comprehensive overview of the importance of cell-cycle deregulation in mesenchymal neoplasia. Paraffin sections of 58 sarcomas and 23 soft-tissue tumors of low malignant potential (STT-LMP) were reacted with monoclonal antibodies against cyclin D1 and p53, using optimized immunohistochemical staining protocols. The staining data were correlated with expression of pRB and p15 and with a variety of pathologic parameters. A total of 33 of 58 sarcomas (57%) and 9 of 23 STT-LMP (39%) overexpressed p53. Fourteen sarcomas (24%) and 4 STT-LMP (17%) overexpressed cyclin D1. There was no correlation between expression of these two genes and histologic tumor type or grade. Loss of RB and loss of p16 or overexpression of cyclin D1 were mutually exclusive events. Considering all four cell-cycle regulators, sarcomas had a significantly higher abnormality rate than did STT-LMP (P < .005). Only 10% of the sarcomas but 39% of STT-LMP showed normal expression of all four gene products. Based on our findings, overexpression of cyclin D1 and (presumably mutant) p53 appear to be among the most common molecular alterations in human mesenchymal neoplasia, and abrogation of cell-cycle control is observed in the great majority of sarcomas; it is present significantly less frequently in low-grade lesions.

Cell Cycle↗
PubMed2000

Murine macrophages stimulated with central and peripheral nervous system myelin or purified myelin proteins release inflammatory products.

Macrophage inflammatory products including tumor necrosis factor (TNF) and interleukin-12/p40 are implicated in demyelinating diseases such as multiple sclerosis (MS), Guillain-Barré syndrome, and animal models experimental autoimmune encephalomyelitis and neuritis. The macrophage product angiotensin converting enzyme (ACE) is released during inflammation. ACE can also be elevated in MS. We investigated the ability of central (CNS) and peripheral nervous system (PNS) myelin to stimulate TNF, interleukin-12, and ACE production by murine macrophages. Both CNS and PNS myelin and purified myelin basic protein and P2 protein induced release of these products. Direct stimulation by myelin may represent a mechanism of inducing release of macrophage products in inflammatory demyelination or neural injury.

Animals↗
PubMed2000

Intrarater and interrater reliability of the MS functional composite outcome measure.

OBJECTIVE: To assess practice effects, and intrarater and interrater reliability of the MS functional composite (MSFC) outcome measure. BACKGROUND: To address the poor reliability and insensitivity to change of available MS clinical rating scales, the National MS Society's Clinical Outcomes Assessment Task Force developed the MSFC, a multidimensional quantitative clinical outcome measure that includes tests of leg function/ambulation (Timed 25-Foot Walk), arm function (Nine-Hole Peg Test), and cognitive function (Paced Auditory Serial Addition Test). METHODS: Ten patients with secondary progressive MS underwent six testing sessions over a 2-week period. The MSFC was administered by the same examining technician in the first five sessions and by the other technician in the sixth. Patients were reassessed by both technicians after 6 months (sessions 7 and 8). The MSFC score was calculated as the mean of the Z scores of the three components. A pooled dataset derived from secondary progressive MS patients in the placebo arms of previous clinical trials and natural history studies served as the reference population to standardize scores. RESULTS: Practice effects were evident initially but stabilized by the fourth administration. The intraclass correlation coefficient (ICC) was 0.97 for the MSFC for session 4 versus session 5 (intrarater reliability). The ICC was 0.95 for session 5 versus session 6 (interrater reliability), and was 0.96 for session 7 versus session 8 when patients were reassessed 6 months later. CONCLUSIONS: The MS functional composite (MSFC) outcome measure had excellent intrarater and interrater reliability when standardized procedures were used to train examining technicians and to assess patients. Prebaseline testing sessions should be included in clinical trials employing the MSFC to compensate for practice effects.

Humans↗
PubMed2000

Glatiramer acetate (Copaxone) treatment in relapsing-remitting MS: quantitative MR assessment.

OBJECTIVE: To evaluate the efficacy of glatiramer acetate (GA, Copaxone; Teva Pharmaceutical Industries, Ltd., Petah Tiqva, Israel) by MRI-based measures in patients with relapsing-remitting (RR) MS. METHODS: Twenty-seven patients with clinically definite RR-MS were treated with either 20 mg of GA by daily subcutaneous self-injection (n = 14) or placebo (n = 13) for approximately 24 months. Axial dual-echo fast-spin-echo T2-weighted images and T1-weighted images before and after gadolinium (Gd) were acquired at 1.5 tesla and transferred into an image processing computer system. The main outcome measures were the number of Gd-enhanced T1 and T2 lesions and their volume as well as brain parenchyma volume. RESULTS: The values of age, disease duration, Expanded Disability Status Scale (EDSS) score, the number of T1- and T2-weighted lesions, and their volume were similar between GA- and placebo-receiving groups at the entry of this study. There was a decrease in the number of T1-enhanced lesions (p = 0.03) and a significant percent annual decrease of their volume in GA recipients compared with those of placebo recipients. There were no significant differences between changes in the two groups in the number of T2 lesions and their volume. The loss of brain tissue was significantly smaller in the GA group compared with that of the placebo group. CONCLUSIONS: These results show that GA treatment may decrease both lesion inflammation and the rate of brain atrophy in RR-MS.

Adult↗
PubMed2000

Predictors of treatment outcome in sexually abused children.

PROBLEM: This study evaluated the impact of child and family characteristics on treatment outcome of sexually abused children. METHOD: Forty-nine recently sexually abused 7- to 14-year-old children were randomly assigned to either abuse-focused cognitive behavioral therapy or nondirective supportive therapy, and assessed pre- and post-treatment using several standardized instruments. These included five measures of psychological symptomatology and four measures of child and family characteristics hypothesized to mediate treatment response. Correlational and multiple regression analyses were utilized to evaluate the impact of the following mediating factors on treatment outcome: Children's abuse-related attributions and perceptions; family cohesion and adaptability; parental support of the child; and parental emotional reaction to the child's abuse. RESULTS: Children's abuse-related attributions and perceptions and parental support of the child were strong predictors of treatment outcome in this population. CONCLUSIONS: Therapeutic attention to children's sexual abuse-related attributions and to enhancing parental support may be important factors in optimizing treatment outcome in 8- to 14-year-old sexually abused children.

Adolescent↗
PubMed2000

The American Society of Anesthesiologists' Physical Status: category V revisited.

STUDY OBJECTIVE: To determine the perioperative mortality and intraoperative morbidity according to operative procedure and postoperative period for American Society of Anesthesiologists' Physical Status (ASA-PS) V category patients. DESIGN: Retrospective chart review. SETTING: University-affiliated medical center. MEASUREMENTS AND MAIN RESULTS: The perioperative records of 111,051 consecutive anesthetized patients, from 1990 to 1997 were retrospectively reviewed. Data were collected and analyzed to determine ASA-PS classification, perioperative mortality, intraoperative morbidity, mortality according to operative procedure, and mortality postoperatively for ASA-PS V patients. At the University of Florida, 0.37% of our patients were ASA-PS V. Most had anesthesia for abdominal (26.2%), cardiothoracic (27.9%), cranial (12.3%), or diagnostic procedures (11.6%). The overall mortality rate decreased in 1993-1995 and 1995-1997, compared to 1990-1993, from 64.16 +/- 4.53 (+/-SD) to 46.7 +/- 9.5 and 56.8 +/- 1.1, respectively. The mortality rate decreased in the immediate postoperative period from 15.7 +/- 5.1 to 4.6 +/- 1.5 and 4.1 +/- 2. 8 intraoperatively, and from 42.5 +/- 1.8% to 22.1 +/- 5.1 and 26.8 +/- 1.8 within 24 hours postoperatively. The mortality rate increased from 0 +/- 0 to 7.4 +/- 3.9 and 15.5 +/- 4.9 (p < 0.05 for all), during the late postoperative period (>2 weeks, during hospitalization). Intraoperative morbidity (untoward events) was significantly higher for ASA-PS V patients than for ASA-PS IV patients only in emergency cases (11.1 +/- 4.8% vs. 5.5 +/- 1.4%). CONCLUSIONS: The ASA-PS V classification is determined subjectively rather than objectively, and can be variable within its parameters, depending on the individual interpretation of ASA classification, patient population, case severity, surgical and anesthesia factors, and the year of the study. Even though immediate perioperative mortality decreased in our patient population, late postoperative mortality increased during the same time period, possibly demonstrating a shift in mortality time rather than an absolute decrease in overall mortality. Although the ASA-PS V category was never intended to be a predictor of outcome, it correlates with perioperative mortality as well as or even better than other classifications of mortality and morbidity. The decreased mortality in the ASA-PS V patient population may be related to different factors, which are beyond the scope of this study.

Anesthesia↗
PubMed2000

Immunoablative high-dose cyclophosphamide without stem cell rescue in a patient with pemphigus vulgaris.

The use of ablative intravenous cyclophosphamide (50 mg/kg per day for 4 days) without stem cell rescue has been described in patients with refractory autoimmune diseases such as paraneoplastic pemphigus, systemic lupus erythematosus, and aplastic anemia. We describe a 33-year-old patient with pemphigus vulgaris recalcitrant to multiple therapies. The patient presented with numerous oral ulcerations, erosions, and hyperpigmented crusted plaques on his face, trunk, and arms. Findings of a skin biopsy and direct immunofluorescence were consistent with pemphigus vulgaris. The circulating pemphigus vulgaris autoantibodies were present at a titer of 1:640. The patient received immunoablative therapy (50 mg/kg of cyclophosphamide for a total of 4 days) and tolerated the regimen well. Complications such as thrombocytopenia and Pseudomonas septicemia were quickly treated. Four months after the 4-day therapy, his oral and skin lesions completely healed, and his pemphigus titers have decreased to zero. He is no longer receiving prednisone and no new lesions have developed. This provides further evidence that this regimen is relatively safe and provides a potential "cure" for refractory autoimmune diseases such as pemphigus vulgaris.

Adult↗
PubMed2000

The potential for vigabatrin-induced intramyelinic edema in humans.

PURPOSE: Vigabatrin (Sabril, Hoechst Marion Roussel) is an antiepilepsy drug (AED) presently marketed in 64 countries for the treatment of partial and secondarily generalized seizures. Vigabatrin (VGB) is marketed in a subset of these countries for the treatment of infantile spasms. Clinical experience in humans has shown that VGB provides effective seizure control with a wide margin of safety. However, animal toxicity studies raised concern when prolonged administration of VGB was shown to induce intramyelinic edema (IME) in some laboratory animal species. METHODS: Animal and human data were reviewed with respect to the potential for VGB-induced IME. Surveillance of patients receiving VGB in clinical trials or by prescription has been conducted for >15 years to identify patients developing clinical abnormalities that might be IME related. RESULTS: The histologic lesions of VGB-induced IME in animals are reliably reproduced and correlate with changes in multimodality evoked potentials (EPs) and magnetic resonance imaging (MRI). Numerous studies of the effects of VGB on EP and MRI in epilepsy patients have demonstrated no clear-cut IME-related changes in these modalities. Additionally, autopsy and surgical brain samples from VGB-treated patients have been scrutinized for potential IME histopathology. In an estimated 350,000 patient-years of VGB exposure (approximately 175,000 patients exposed for 2 years at an average dose of 2 g/day), no definite case of VGB-induced IME has been identified. CONCLUSIONS: Comprehensive review of a variety of sources of data failed to identify any definite case of IME in humans treated with VGB.

Animals↗
PubMed2000

Treatment for sexually abused children and adolescents.

The authors review research demonstrating the variable effects of childhood sexual abuse, the need for intervention, and the effectiveness of available treatment models. The well-controlled treatment-outcome studies reviewed do not focus on sensationalistic fringe treatments that treat sexually abused children as a special class of patients. Instead, studies demonstrate empirical evidence for extending and modifying treatment models from mainstream clinical child psychology to sexually abused children. The authors propose a continuum of interventions to meet the needs of this heterogeneous group. Interventions range from psychoeducation and screening, to short-term, abuse-focused cognitive-behavioral therapy with family involvement, to more comprehensive long-term plans for multiproblem cases. Last discussed are gaps in the research and suggestions for future research to address the pressing dilemmas faced by clinicians and policymakers.

Adolescent↗
PubMed1999

Therapy of relapsing multiple sclerosis. Treatment approaches for nonresponders.

There is increasing impetus to begin disease-modifying therapy for relapsing multiple (R-MS) early, before the development of irreversible tissue damage and resultant permanent disability. However, all of the currently-approved therapies for relapsing multiple sclerosis are only partially effective for patients as a group. Treatment failure can be due to noncompliance with therapy, intolerable adverse effects, the development of neutralizing antibodies, or non-responsive disease. Neurologists managing patients on disease-modifying therapy for R-MS must remain vigilant for these issues and take appropriate action when necessary.

Anti-Inflammatory Agents↗
PubMed1999

Suture loop to aid in ganciclovir implant removal.

BACKGROUND: The ganciclovir implant (Vitrasert; Bausch & Lomb Inc, Claremont, Calif) has been a useful device in the management of cytomegalovirus retinitis. Seven months after placement, implant exchange is often considered. However, removal may be difficult and may result in vitreous hemorrhage or intraocular dislocation. OBJECTIVE: To describe a suture loop attached to the implant strut and left in the sub-Tenon space to aid in implant removal. METHODS: Twenty-five eyes of 17 patients received a ganciclovir implant with an 8-0 nylon suture loop left beneath the Tenon capsule and underwent at least 6 months of follow-up. Two of these eyes subsequently had a similarly modified ganciclovir implant placed at a separate site (inferonasally) with at least 6 additional months of follow-up. Six eyes of 3 patients had the implant removed as part of an exchange and underwent at least 4 months of follow-up. RESULTS: In the 25 eyes, there were no cases of endophthalmitis, wound leak, suture exposure, or other complications. At implant removal in the 6 eyes previously mentioned, the loop was used for traction on the implant and aided in localization of the implant strut. In these 6 eyes, there were no cases of retinal or choroidal detachment, visually significant vitreous hemorrhage, implant dislocation, or other complications. CONCLUSION: A sub-Tenon capsule suture loop is well tolerated and can assist in ganciclovir implant removal.

Adult↗
PubMed1999

Total homocysteine is associated with nephropathy in non-insulin-dependent diabetes mellitus.

Non-insulin-dependent diabetes mellitus (NIDDM) and hyperhomocysteinemia are both associated with premature vascular disease. We tested the hypothesis that homocysteine is associated with vascular disease and other diabetic complications in patients with NIDDM. The current investigation is a cross-sectional analysis of baseline variables for participants in the Appropriate Blood Pressure Control in Diabetes (ABCD) Trial. Men and women aged 40 to 74 years with NIDDM and a mean diastolic blood pressure (BP) of 80 mm Hg or higher were eligible. We measured serum levels of total homocysteine (tHcy), cystathionine, and methylmalonic acid (MMA) and correlated these values with clinical and other laboratory measures of the complications of diabetes mellitus in 452 subjects. tHcy was higher in males than in females and correlated with the duration of hypertension and systolic BP. tHcy was significantly correlated with MMA (r = .35, P < .0001) and cystathionine (r = .53, P < .0001) levels and inversely correlated with serum B12 (r = -.23, P < .0001) and folate (r = -.18, P < .0001). It was significantly correlated with serum creatinine (r = .28, P < .0001 for males and r = .39, P < .0001 for females) and inversely correlated with creatinine clearance (r = -.19, P < .005 for males and r = -.30, P < .0001 for females). tHcy was not increased in subjects with cardiovascular disease or retinopathy, but it was increased in those with neuropathy (10.3 v 9.3 micromol/L, P < .05) and macroalbuminuria (11.0 v 9.2 micromol/L, P < .005). Of these subjects, 2.2% met the criteria for vitamin B12 deficiency and 1% met the criteria for folate deficiency. We conclude that elevations of tHcy in this population appear to be the result of a combination of vitamin deficiency and decreased renal function and do not appear to be a predictor of cardiovascular disease.

Adult↗
PubMed1999

Sumatriptan treatment for migraine in a health maintenance organization: economic, humanistic, and clinical outcomes.

This study was undertaken to assess the impact of 12 months of sumatriptan therapy (6 mg subcutaneously) for migraine on health care use, health-related quality of life, productivity, patient satisfaction with the medication, and clinical efficacy in a health maintenance organization (HMO). One hundred forty-eight patients received open-label sumatriptan for 12 months for the treatment of migraine. Medical records were reviewed to obtain information on the frequency of migraine-related health care use during the 12 months before and during sumatriptan treatment. Patients completed questionnaires on their productivity at work, health-related quality of life, and satisfaction with medication at baseline and after 3, 6, and 12 months of sumatriptan treatment. For each migraine, patients recorded pain severity scores before and after taking sumatriptan and the time between dosing and onset of meaningful relief. Sumatriptan was associated with significant reductions in migraine-related use of general outpatient services, telephone calls, urgent care services, and emergency department visits (P < 0.05); a significant increase in the use of pharmacy services (P < 0.05); and significant and sustained improvements in health-related quality-of-life scores compared with baseline (P < 0.001). Patients lost significantly less time from work and were significantly more satisfied with sumatriptan compared with their usual therapy (P < 0.05). Two hours after dosing, 81% of patients experienced reduction of moderate or severe pain to mild or no pain, and 90% of all patients experienced meaningful relief of pain. The use of sumatriptan for 12 months in an HMO was associated with reductions in health care use and improved health-related quality of life, productivity, and patient satisfaction with medication.

Adult↗
PubMed1999

Quantification of axonal damage in traumatic brain injury: affinity purification and characterization of cerebrospinal fluid tau proteins.

Diffuse axonal injury is a primary feature of head trauma and is one of the most frequent causes of mortality and morbidity. Diffuse axonal injury is microscopic in nature and difficult or impossible to detect with imaging techniques. The objective of the present study was to determine whether axonal injury in head trauma patients could be quantified by measuring levels of CSF tau proteins. Tau proteins are structural microtubule binding proteins primarily localized in the axonal compartment of neurons. Monoclonal antibodies recognizing the form of tau found in the CSF of head trauma patients were developed by differential CSF hybridoma screening using CSF from head trauma and control patients. Clones positive for head trauma CSF tau proteins were used to characterize this form of tau and for ELISA development. Using the developed ELISA, CSF tau levels were elevated >1,000-fold in head trauma patients (mean, 1,519 ng/ml of CSF) when compared with patients with multiple sclerosis (mean, 0.014 ng/ml of CSF; p < 0.001), normal pressure hydrocephalus (nondetectable CSF tau), neurologic controls (mean, 0.031 ng/ml of CSF; p < 0.001), or nonneurologic controls (nondetectable CSF tau; p < 0.001). In head trauma, a relationship between clinical improvement and decreased CSF tau levels was observed. These data suggest that CSF tau levels may prove a clinically useful assay for quantifying the axonal injury associated with head trauma and monitoring efficacy of neuroprotective agents. Affinity purification of CSF tau from head trauma patients indicated a uniform cleavage of approximately 18 kDa from all six tau isoforms, reducing their apparent molecular sizes to 30-50 kDa. These cleaved forms of CSF tau consisted of the interior portion of the tau sequence, including the microtubule binding domain, as judged by cyanogen bromide digestion. Consistent with these data, CSF cleaved tau bound taxol-polymerized microtubules, indicating a functionally intact microtubule binding domain. Furthermore, epitope mapping studies suggested that CSF cleaved tau proteins consist of the interior portion of the tau sequence with cleavage at both N and C terminals.

Alzheimer Disease↗