Jacob Sage - Academia.edu (original) (raw)

Papers by Jacob Sage

Biological Psychiatry, Apr 1, 1993

Clinical Genetics, Apr 23, 2008

The dopamine D4 receptor (D4DR) has a highly polymorphic region in the third exon which has been ... more The dopamine D4 receptor (D4DR) has a highly polymorphic region in the third exon which has been associated with novelty seeking (NS) behavior. Due to the central position of dopamine and the documented low NS in Parkinson&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease (PD), the frequency of the exon 3 variants of D4DR in 95 PD patients and 47 controls was investigated. A significantly higher frequency of exon 3 alleles with six or more repeat units was found in the PD group (p = 0.039). This provides evidence that some forms of the highly polymorphic D4DR may represent a genetic susceptibility factor for PD.

Clinical Neuropharmacology, Apr 1, 1988

Neurology, Jul 1, 1992

We report two patients with a primarily akinetic form of parkinsonism who were nonresponsive to t... more We report two patients with a primarily akinetic form of parkinsonism who were nonresponsive to treatment with levodopa. At autopsy, both patients had many Lewy bodies in brainstem and diencephalic nuclei, with sparse Lewy bodies in association cortices and more numerous Lewy bodies in the limbic cortices, consistent with the transitional form of Lewy body disease. These cases emphasize that (1) Lewy body Parkinson&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease cannot be excluded on the basis of atypical presentation or levodopa nonresponsiveness, and (2) the clinicopathologic spectrum of Lewy body disease is varied.

Psychiatric Genetics, 1998

A deletion polymorphism in the serotonin transporter-linked polymorphic region (5-HTTLPR) has bee... more A deletion polymorphism in the serotonin transporter-linked polymorphic region (5-HTTLPR) has been associated with vulnerability to affective disorders, yet the mechanism by which this gene confers vulnerability remains unclear. Two studies examined associations between the 5-HTTLPR polymorphism and attentional bias for emotional stimuli among nondepressed adults. Biased attention, attention engagement, and difficulty with attention disengagement were assessed with a spatial cuing task using emotional stimuli. Results from Study 1 (N ϭ 38) indicated that short 5-HTTLPR allele carriers experienced greater difficulty disengaging their attention from sad and happy stimuli compared with long allele homozygotes. Study 2 participants (N ϭ 144) were genotyped for the 5-HTTLPR polymorphism, including single nucleotide polymorphism rs25531 in the long allele of the 5-HTTLPR. Consistent with Study 1, individuals homozygous for the low-expressing 5-HTTLPR alleles (i.e., S and L G) experienced greater difficulty disengaging attention from sad, happy, and fear stimuli than high-expressing 5-HTTLPR homozygotes. Because this association exists in healthy adults, it may represent a susceptibility factor for affective disorders that becomes problematic during stressful life experiences.

Movement Disorders, 1990

Ten patients with idiopathic Parkinson's disease and motor fluctuations were rated for mood chang... more Ten patients with idiopathic Parkinson's disease and motor fluctuations were rated for mood changes during discrete "off," "on," and "on with dyskinesia" periods. The Profile of Mood States and visual analogue scales were used. Significant changes in mood and anxiety were found to parallel changes in motor fluctuations. One patient rated his moods as consistently improving from the "off' state to the "on" state and finally to the "on with dyskinesia" state, a finding that is consistent with concomitant central dopaminergic changes. All other patients showed moods that improved significantly from the "off" state to the "on" state but then worsened significantly in the "on with dyskinesia" state, a finding that is consistent with the fact that patients feel worse when impaired by dyskinesias. It is suggested that these results argue for multiple etiologies of depression in Parkinson's disease. The literature on dopamine and depression in Parkinson's disease is briefly reviewed and the opportunity provided by "on-off" phenomena to study the effect of dopamine on mood changes is discussed.

Neurology, Oct 1, 1996

Worth of neurologists To the Editor: The recent article by Hillen and Sage' addressing the issue ... more Worth of neurologists To the Editor: The recent article by Hillen and Sage' addressing the issue of qualitative improvements in care by specialist consultants was a welcome initiation, though perhaps open to the liability of self-defeat. Following the guidelines of these authors, a consultant would be considered "useful" for merely suggesting a ridiculous diagnosis, effecting a procedure to rule it out a t whatever cost, and proposing a misguided treatment regimen. Primary care physicians and payors may not be sympathetic to this point of view. Perhaps we should begin by quantifying the specialist as a cost-effective physician, which is dif€icult enough. My impression about my own activity, which many neurologists will surely share, is that in neurological matters, I am fiscally, as well as diagnostically and therapeutically, efficient. Primary care physicians obtain imaging studies, electrical studies, and other common and exotic laboratory data that I would not have needed. Patients arrive on multiple drugs where fewer would serve better, and end up in Emergency Rooms more frequently without an involved and accessible subspecialist. We would, I think, do better to restrict much technology to conscientious subspecialist control. All this so far is merely an impression, but it is subject to quantification, which we badly need if we are to make a good argument for our co-dominant role. I would suggest that we begin, individually and collectively, to amass and quantify the experience that will validate our selfesteem; not neglecting, but perhaps deferring, the more difficult issues of qualitative satisfaction which may have to do more with ethics than with reimbursement schemata.

Journal of General Internal Medicine, Oct 1, 1994

Medical Hypotheses, Feb 1, 1989

Recent developments have focused attention on the possibility that a toxic environmental factor m... more Recent developments have focused attention on the possibility that a toxic environmental factor may be the cause of Parkinson's disease (PD). A hypothesis seeking to explain the cause of PD must explain its worldwide distribution, the small percentage of the population affected, geographic variations in prevalence and why PD was unrecognized prior to the early nineteenth century. The difficulties in finding a ubiquitous environmental agent which could account for these observations, may be illustrated by considering the hypothesis that such an agent may be a constituent of a common plant such as the tomato. This hypothesis meets all .the necessary prerequisites. It is testable and appears to be an excellent starting point from which to search for the cause of PD.

Annals of Neurology, Oct 1, 1991

LeWitt PA, Calne DB. Pleuropulmonary changes during longterm bromocriptine treatment for Parkinso... more LeWitt PA, Calne DB. Pleuropulmonary changes during longterm bromocriptine treatment for Parkinson's disease. Lancet Corrodi H, Fuxe K, Hokfelt T, et al. Effect of ergot drugs on central catecholamine neurons: evidence for a central dopamine.

Archives of neurology, Jul 1, 1983

Ipsilateral cerebellar and pyramidal signs suddenly developed in three patients. Computed tomogra... more Ipsilateral cerebellar and pyramidal signs suddenly developed in three patients. Computed tomography revealed small infarcts of the corona radiata in two patients and a small infarct in the posterior limb of the internal capsule in the third. Ataxic hemiparesis can result from lesions of the corona radiata as well as many other points along the corticopontine pathways.

Stroke, 1984

Brain unidirectional extraction and flux of leucine were measured simultaneously with cerebral bl... more Brain unidirectional extraction and flux of leucine were measured simultaneously with cerebral blood flow (CBF) at various times after transient global cerebral ischemia in the rat. The results permit an evaluation of blood-brain barrier permeability in the postischemic period independent of alterations in CBF at the time of measurement. Leucine extraction was higher (p < 0.001) than that of CBFmatched controls at 15 min and 6 hr after 30 min of global cerebral ischemia, but was not different from control at 30 min and 1 h after ischemia. Leucine flux into brain was increased only at 15 min after reperfusion of the brain. Cerebral edema occurs 15-30 min after reperfusion in this ischemia model, but the permeability of the blood-brain barrier to large molecules is unaltered during this period (Petito et al: J Neuropath Exp Neurol 41:423-436, 1982). Increased barrier permeability to small molecules such as leucine may contribute to the production of this early postischemic edema.

Alzheimer's disease non-alzheimer dementing disorders acute confusion and delirium gait distu... more Alzheimer's disease non-alzheimer dementing disorders acute confusion and delirium gait disturbances and cervical spondylosis myasthenia gravis in the elderly myopathic disorders neuropathic disorders fatigue sleep in the elderly: overview and selected disorders headache and neuralgias the interpretation of neurophysiologic studies in the elderly social and legal issues in geriatric neurology hyperkinesias and drug-induced movements disorders Parkinson's disease in the elderly atypical Parkinsonism diffuse Lewy body disease the borderline of psychiatry and neurology cerebral vascular disease visual disorders dizziness seizures neuro-urology infections of the nervous system neurorehabilitation.

Springer eBooks, 2019

ABSTRACT http://link.springer.com/chapter/10.1007/978-1-4614-9449-2\_10/fulltext.html

Annals of Pharmacotherapy, Mar 1, 1995

To review the pharmacokinetics and use of apomorphine in patients with Parkinson&amp;#39;... more To review the pharmacokinetics and use of apomorphine in patients with Parkinson&amp;#39;s disease; to report a case of beneficial outcome with apomorphine in a patient with Parkinson&amp;#39;s disease with severe levodopa &amp;quot;on-off&amp;quot; fluctuations and freezing; and to outline the types of patients or situations where apomorphine may be useful. Case reports, review articles, and relevant clinical studies identified by a MEDLINE search of the English-language literature published between 1975 and October 1994. Because all but 2 reports were of open-label design with small sample sizes, all studies identified were evaluated. The following data were extracted from each study: apomorphine treatment duration, dosing, onset, duration, and adverse effects. The following efficacy variables were extracted: percent decrease in off periods, improvement in parkinsonian symptoms, and percent decrease in levodopa dosage. Efficacy of apomorphine following subcutaneous, rectal, sublingual, and intranasal dosage forms are evaluated. We also describe the use of apomorphine in a patient with Parkinson&amp;#39;s disease who experienced on-off fluctuations and freezing. Based on these reports, recommendations for patient selection, product selection, and apomorphine dosing guidelines are presented. Apomorphine decreases off time, freezing, and levodopa requirements in patients with Parkinson&amp;#39;s disease. It can be administered via a number of different nonoral routes; however, subcutaneous apomorphine is the most extensively studied. Rectal, sublingual, and intranasal routes also have been shown to provide benefit in motor fluctuations, but differ from the subcutaneous route in onset of action, duration of effect, and adverse effect profile.

Stroke, 1983

One-hundred-forty patients with atrial fibrillation (AF) due to non-rheumatic, non-valvular heart... more One-hundred-forty patients with atrial fibrillation (AF) due to non-rheumatic, non-valvular heart disease (NVHD) who suffered a cerebral infarct were identified. Fifty-three (38%) died of the initial stroke. The surviving patients were followed up to 9 years without anticoagulant therapy. In the 59 patients available for follow-up, the risk of recurrent cerebral ischemia remained at approximately 20% per year throughout the 9 year observation period. The recurrence rate was the same regardless of age, sex, previous myocardial infarction, or whether chronic AF or intermittent AF were present. Only 7 (12%) died from a second stroke, however. The high annual rate of recurrence and lack of controlled therapeutic trials in this population of patients warrant a prospective study to define the benefits and relative risks of anticoagulant therapy in AF due to NVHD.

Neurology, 1996

The cause of progressive supranuclear palsy (PSP) is not known and has been little studied.The on... more The cause of progressive supranuclear palsy (PSP) is not known and has been little studied.The one previous controlled epidemiologic survey, performed at our center in 1986, found small-town experience and greater educational attainment as PSP risks, but, in retrospect, these results may have been produced by ascertainment bias. Since that time, several anecdotal reports have implicated heredity and various environmental exposures in the cause of some cases of PSP. To clarify the results of the previous study and to evaluate the more recently implicated candidate factors in a controlled fashion, we mailed a validated 69-item questionnaire to 91 personally examined patients with PSP and 104 unmatched controls with other neurologic conditions for which they had been referred to our tertiary neurologic center. We were able to match 75 subjects from each group by year of birth, sex, and race and subjected them to a separate matched-pair analysis. We allowed surrogates to supply any or a...