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Inflammatory mechanisms in the brain may contribute to the neurodegenerative process in Alzheimer's disease. The cerebral acute-phase response mediated by inflammatory cytokines, the complement cascade, and the accumulation of activated microglial cells are appropriate targets for anti-inflammatory intervention. Pilot studies showed that tolerable doses of prednisone suppress the peripheral acute-phase response in Alzheimer's disease, and a multicenter therapeutic trial of prednisone is in progress. Two other anti-inflammatory drugs, hydroxychloroquine and colchicine, are also under investigation.

Preliminary to a multicenter trial, an open-label study was conducted of prednisone treatment in Alzheimer's disease. Prednisone was given at an initial dose of 10 mg (part 1) or 20 mg (part 2) and tapered over 7 weeks. There were no serious adverse events attributed to the medication, and there were no significant changes in either mean cognitive or behavioral assessment scores with treatment during either part. Serum levels of the acute phase proteins alpha-1-antichymotrypsin and C-reactive protein did not change significantly during part 1, but were suppressed by the higher dose given in part 2. Thus, a prednisone regimen with an initial dose of 20 mg is tolerable and results in suppression of the acute phase response in Alzheimer's disease.

We studied the effect of the inflammatory cytokine interleukin-1 beta (IL-1) and several anti-inflammatory drugs on amyloid beta-peptide (A beta) cytotoxicity. Incubation of PC12 cells with 10(-6) M A beta 1-42 for 24 h reduced viabilty to 36%; coincubation with 10(-7) M IL-1 further reduced viability to 13% of baseline. With preincubation of PC12 cells with the drugs indomethacin, dexamethasone and chloroquine, reduction in viability was limited to 51%, 48% and 44%, respectively, compared to 32% with A beta alone. These experiments support further study of anti-inflammatory therapy in Alzheimer's disease.

Inflammatory mechanisms are active in patients with Alzheimer disease. Serum elevations of acute phase proteins such as alpha 1-antichymotrypsin, along with deposition of inflammatory cytokines in the brain, suggest a "cerebral acute phase response" contributing to amyloid deposition and tissue destruction. Activated microglia possessing HLA-DR surface markers accumulate around amyloid plaques. The complement cascade leads to generation of the membrane attack complex, which may directly damage neuronal membranes. This growing body of evidence suggests that empirical trials of anti-inflammatory drugs are now appropriate to test the hypothesis that suppression of these mechanisms will slow the rate of progression of Alzheimer disease. Several drugs useful in the treatment of rheumatic diseases are candidates for study in Alzheimer disease, including glucocorticoids, antimalarial drugs, and colchicine. Pilot studies of the synthetic glucocorticoid prednisone indicate that treatment with a moderate dose is well tolerated in patients with Alzheimer disease, and suppresses serum levels of acute phase proteins. Based on this experience, a multicenter parallel-design placebo-controlled trial has been initiated with Alzheimer's Disease Cooperative Study to determine whether treatment with prednisone can slow the rate of progression of Alzheimer disease.

The rapidly growing discipline of medical informatics is changing the face of clinical practice and research. The author reviews current efforts toward the development of electronic medical record systems. A successful system must provide satisfactory solutions to five major requirements: a user interface acceptable to varied health care personnel, data storage and transmission standards that will allow communication with other systems, a coding system that is flexible but accommodates complex queries, a multilevel security structure and audit trail, and unique identifiers for patients and providers. These issues have not been fully resolved, and replacement of paper charts with fully computerized records is many years away, but the application of readily available computer tools to geriatric psychiatry can yield immediate benefits. The author describes a supplemental record system that provides improved organization of clinical information as well as powerful search capabilities., (Copyright © 1996 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

To determine the utility of the sympathetic skin response (SSR) in studying sympathetic outflow in cervical spinal cord injury (CSCI) patients who develop features of reflex sympathetic dystrophy, we studied seven consecutive CSCI patients with the shoulder-hand syndrome (SHS), and seven patients with similar injuries but without the manifestations of the SHS. The mean SSR amplitude was more than three times greater in patients with the SHS, a statistically significant difference. We restudied six patients with a SHS after symptoms had improved following steroid treatment: the mean amplitude fell significantly, approaching the mean for the control group. When pain was asymmetric, the SSR amplitude was higher in the arm with greater pain. Four of the seven SHS patients demonstrated an unusual pattern of spontaneous cyclical electrical activity during a period of severe pain. We conclude that a SHS complicating CSCI is associated with increased amplitude of the SSR, supporting the theory that sympathetic hyperactivity is important in the pathophysiology of reflex sympathetic dystrophy in this setting.

We conducted a retrospective case-control study of falls over a four year period on a 30 bed neurorehabilitation unit at the Burke Rehabilitation Hospital to characterize the nature of falls and identify factors associated with falling. The most common diagnoses treated on the unit were traumatic spinal cord injury, brain injury, and multiple sclerosis; stroke patients are treated on another service. Falls represented 72 percent of all incident reports made to the Nursing Office during the study period. One hundred seventeen (117) falls occurred in 82 patients during a time when the unit census was 28,622 patient days, yielding a rate of 1,439 falls per 1,000 patient years. One hundred fourteen (114) patients admitted with no history of falling during the same period were selected randomly for comparison. Most falls were associated with no injury (n = 96) or minor injury (n = 18). The most significant injuries occurred in three cases with lacerations requiring sutures. Falls occurred with greatest frequency during the first and fourth quartiles of the hospital stay, during the evening and while bed transfers were being performed. No association between falling and patient age, sex, diagnosis, number of medications, use of sedating medications, presence of motor, visual or cognitive impairment or orthostatic hypotension was evident. An increased risk of falling was associated with physician orders for Posey restraints. The implication of these findings for falls prevention programs is discussed.

To characterize the occurrence of shoulder-hand syndrome (SHS) complicating the rehabilitation of patients with cervical spinal cord injury, we reviewed the medical records of 43 consecutive patients admitted to the Burke Rehabilitation Center with cervical spinal cord injury, focusing on the clinical features of SHS: shoulder pain, hand/wrist pain, edema, vasomotor changes, trophic changes and osteoporosis on x-ray. Twenty-seven patients (63%) had three or more features of SHS. The number of features correlated with age (r = 0.495, p = 0.0007), but not with the presence of upper or lower motor neuron findings in the arms, or with autonomic dysfunction. Twenty-three of 25 (92%) SHS patients with adequate follow up had satisfactory resolution of symptoms with conservative therapy (i.e. neither systemic corticosteroids nor stellate ganglion block), but only after a mean of 121 days (range 42-274 days).

To assess the feasibility of one approach to combined cholinergic/noradrenergic treatment in Alzheimer's disease, ten patients were enrolled in a 2-week placebo-controlled study of oral physostigmine plus clonidine. The Alzheimer's Disease Assessment Scale (ADAS) was used as the primary outcome measure. Neither physostigmine alone, nor the combination of physostigmine plus clonidine, was associated with a statistically significant improvement for the group. Three patients did show an improvement of at least 4 points on the total ADAS score with the drug combination. The implications of these results for treatment strategies are discussed.

Objective: The purpose of this article is to review evidence that inflammatory and immune mechanisms are important in the pathophysiology of Alzheimer's disease and to suggest new treatment strategies., Method: The authors review the English-language literature of the last 10 years pertaining to the pathophysiology of Alzheimer's disease., Results: There is ample evidence supporting the hypothesis that inflammatory and immune mechanisms are involved in tissue destruction in Alzheimer's disease. Acute phase proteins are elevated in the serum and are deposited in amyloid plaques, activated microglial cells that stain for inflammatory cytokines accumulate around senile plaques, and complement components including the membrane attack complex are present around dystrophic neurites and neurofibrillary tangles., Conclusions: Clinical trials of anti-inflammatory/immunosuppressive drugs are necessary to determine whether alteration of these inflammatory mechanisms can slow the progression of Alzheimer's disease.

To examine factors associated with prolonged length of stay (LOS) on an inpatient, acute geropsychiatry service, the authors reviewed electronic medical records and social work files for patients discharged during a 12-month period. There was no significant correlation between LOS and age, medical comorbidity, or the presence of dementia, depression, or psychosis. Patients transferred to adult homes or nursing homes stayed twice as long as patients who returned to their own homes (84 vs. 41 days; P= 0.002). Discharge disposition (rather than clinical factors) is associated with prolonged LOS in geropsychiatry and should be the focus of efforts to shorten hospital stays., (Copyright © 1994. Published by Elsevier Inc. All rights reserved.)

Pulmonary embolism is a common, sometimes fatal complication of spinal cord injury. We describe two quadriplegic patients who developed unexplained fever as the sole presenting sign of multiple pulmonary emboli during the subacute phase following injury. These cases and a review of the literature suggest that ventilation-perfusion scanning should be considered in the diagnostic evaluation of fever in patients with recent spinal cord injury even in the absence of other clinical signs of thromboembolic disease.

Effective symptomatic treatment of Alzheimer's disease (AD) may require a combination of agents that augment cholinergic as well as noradrenergic neurotransmission. We conducted a pilot study of physostigmine plus oral yohimbine challenge in AD. Ten patients were enrolled in a 12-day double-blind protocol. Each patient received placebo q2h while awake for 5 days, followed by physostigmine 2 mg q2h while awake for 7 days. During each of these drug conditions, yohimbine challenges were administered at oral doses of 10 and 20 mg in a placebo-controlled manner. There was no significant improvement in Alzheimer's Disease Assessment Scale test performance for six patients for whom complete cognitive data were obtained for the 6 challenge days. Nine patients tolerated the protocol with no clinically significant changes in blood pressure, pulse, or electrocardiogram (ECG), and no cardiovascular, gastrointestinal, or autonomic toxicity. One patient complained of chest discomfort associated with tachycardia, a modest rise in blood pressure, and had t-wave inversion in a single precordial lead. These signs and symptoms resolved within a few hours. Serial ECG tracings and cardiac enzymes revealed no evidence of myocardial injury. This pilot study did not reveal major cognitive improvement with this regimen, but underscores the importance of careful cardiovascular monitoring during future combined cholinergic-noradrenergic therapies in AD.

A patient with probable Alzheimer's disease participated in four studies involving cholinergic and combination cholinergic/noradrenergic treatment regimens. This patient demonstrated clinically significant improvement only with the combination of physostigmine and clonidine. The implications of these findings are discussed with regard to strategies for neurotransmitter augmentation therapy for Alzheimer's disease., (Copyright © 1993 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

We have implemented a clinical management software system for an academic Geropsychiatry Division that allows us to gain many benefits of a computerized medical record system with minimal development and maintenance expense. We use brief electronic records to capture key information, combining coded and free-text formats. Data entry is fast and simple, readily accomplished by physicians during clinical rounds (for inpatients), or by clerk (from outpatient encounter forms). Sufficient clinical data is stored to be useful in patient management, and to support administrative and clinical research functions.

Elderly patients with psychiatric disorders present a formidable clinical challenge. Medical and psychiatric disorders coexist and mimic each other, blurring diagnostic criteria. Accurate diagnosis is essential and can best be achieved by cooperation between internist and psychiatrist. Most treatments carry substantial risk, which must be minimized by careful medical assessment and optimal selection among options. Error is unavoidable, so clinicians must continually analyze and question their diagnostic and therapeutic decisions.

Episodes of fever, serositis, and arthritis in familial Mediterranean fever (FMF) suggested circulating mediators of acute inflammation (e.g., neutrophil activation). The mean serum neutrophil-aggregating activity of 51 FMF patients was 2.5 +/- 0.2 cm2/min, compared to 1.0 +/- 0.1 cm2/min in 20 normal controls (P less than 0.0002). Lipid extracts of FMF sera retained neutrophil-aggregating activity and had UV absorbance peaks at 269 and 279 nm, indicating the presence of lipids with a conjugated triene structure. Chromatography of extracts yielded peaks that were coeluted with reference dihydroxyicosatetraenoic acids, had UV absorbance peaks at 259, 269, and 279 nm, and possessed neutrophil-aggregating activity. The presence of leukotriene B4 was excluded by chromatography following methyl-esterification. Monohydroxy compounds identified in FMF extracts by gas chromatography/mass spectrometry included 5-hydroxyicosatetraenoic acid, and 9- and 13-hydroxyoctadecadienoic acids. Hydroxy acids were present in 19 of 31 FMF sera and absent in extracts of sera from 8 patients with active systemic lupus erythematosus, 7 with fever from infection, and 12 normal controls. The finding of circulating mono- and dihydroxy fatty acids in FMF suggests that defects in the formation or elimination of these compounds might play a role in the pathogenesis of FMF.

The significance of hypochondriacal complaints in elderly depressives was explored. Sixty percent of patients had such symptoms on admission. Twelve percent were delusional. At discharge, hypochondriasis was present in 40% of the sample, with 0% delusional. Hypochondriasis was associated with anxiety (P less than .05) and somatic concerns (P less than .001), but not with complaints of depressed mood, suicidality, or short-term outcome. In dependent physical illness ratings did not correlate with hypochondriasis, however nonpsychotropic medication use did (P less than .01). Improvement in hypochondriacal complaints with treatment, yet persistence of less intense hypochondriacal concerns after remission suggests that these features may represent an admixture of state and trait phenomena in elderly depressives.

Occult foreign body aspiration is an uncommon but serious occurrence in the elderly population. A case is presented in which the foreign body, a nut, was uncovered only at autopsy.