Biomedical subjects
Publications and source records attributed to J M Silver.
A case of a 14-year-old girl who developed a spinal subdural hematoma after placement of a ventriculoperitoneal shunt is presented. Such a complication has not been previously reported. We believe that this represented an extension of intracranial subdural hematoma fluid into the spinal subdural space.
Gangliogliomas are uncommon tumors of mixed neoplastic glial and neuronal elements. Because of their low incidence, few large series exist that fully describe the clinical characteristics of patients afflicted with this tumor. We have reviewed the medical records of 20 patients at Duke University Medical Center with histologically proven gangliogliomas. These patients typically presented within the first three decades of life and their most common presenting symptom was seizures. Therapies included surgical resection, either partial or total, radiation therapy, and/or chemotherapy. Long-term follow-up was achieved by chart review and by telephone interview. Patients who underwent gross total resection alone seemed to fare the best when comparing all treatment groups, and we therefore recommend this as the main form of treatment.
To evaluate the possibility that abnormal regulation of benzodiazepine receptor (BZR) function may relate to the pathophysiology of anxiety disorders, two doses of the BZR antagonist flumazenil (Ro 15-1788) and placebo were administered to panic disorder patients in a double-blind, randomized, crossover design. All 11 patients received flumazenil (600 mg). Ten of the 11 also received flumazenil (200 mg), and 8 of the 11 were given matching placebo capsules orally on separate test days. Neither dose of flumazenil showed significant anxiolytic effects or significantly altered heart rate, blood pressure, or levels of plasma cortisol or 3-methoxy-4-hydroxyphenylglycol in comparison to placebo. On 200 mg days, anxiety ratings on a visual analog scale significantly increased compared to placebo at 30 min and then returned to baseline levels. Panic attacks occurred on placebo, 200 mg, and 600 mg days in 0/8, 4/10, and 0/11, respectively. Failure to observe anxiolytic effects suggests that flumazenil at these doses does not antagonize a tonic increased interaction of BZRs with an endogenous BZR inverse agonist in panic patients.
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Issues related to the epidemiology, nosology, and differential diagnosis of organic aggressive disorders in the elderly are discussed. Rating and monitoring of aggressive events using the Overt Aggression Scale are reviewed. The management of acute aggression with antipsychotic agents and benzodiazepines is presented, as well as an approach for using beta-blockers, anticonvulsant agents, and serotonin-specific antidepressants and an antianxiety agent for the treatment of chronic aggression.
Posttraumatic stress disorder (PTSD) may develop after exposure to severe stress, such as combat, accidents, assaults, and natural disasters. Pharmacotherapy can be a useful adjunct in the comprehensive treatment of these patients. The presence of comorbid conditions, including depression, panic disorder, substance abuse, and traumatic brain injury, should be carefully evaluated. Symptoms of PTSD that are associated with central nervous system hyperarousal or reexperiencing of the traumatic event appear to be the most responsive to pharmacotherapy. Social withdrawal and dulled responsiveness have not been shown to be alleviated through standard pharmacologic interventions. A therapeutic strategy is proposed that is based on the patient's symptoms and initial response to medication.
The Observer's Assessment of Alertness/Sedation (OAA/S) Scale was developed to measure the level of alertness in subjects who are sedated. This scale was tested in 18 subjects in a three-period crossover study to assess its reliability and its criterion, behavioral, and construct validity. After receiving either placebo or a titrated dose of midazolam to produce light or heavy sedation, each subject was administered two sedation scales (OAA/S Scale and a Visual Analogue Scale) and two performances tests (Digit Symbol Substitution Test and Serial Sevens Subtraction). Two raters individually evaluated the subject's level of alertness on each of the two sedation scales. The results obtained on the OAA/S Scale were reliable and valid as measured by high correlations between the two raters and high correlations between the OAA/S Scale and two of the three standard tests used in this study. The OAA/S Scale was sensitive to the level of midazolam administered; all pairwise comparisons were significant (p less than 0.05) for all three treatment levels at both test periods.
Depression occurs frequently in patients with neurologic disorders. Current research in traumatic brain injury, stroke, Parkinson's disease, multiple sclerosis, epilepsy, and brain tumors indicates that affective symptomatology can be a specific sequel of these illnesses that is related to the resultant impairment in brain functioning. Because of the cognitive and emotional deficits that neurologic disorders can cause, the clinician must be aware of the complicated presentation of depression in these patients. Psychopharmacologic treatments are safe and efficacious in the treatment of depression in patients with neurologic illness.
Monoamine oxidase inhibitors (MAOIs) are increasingly used for patients who do not respond to an initial trial of tricyclic antidepressants (TCAs). Although there are insufficient data documenting the optimal manner for switching a patient from a TCA to an MAOI, standard references advise a drug-free interval of at least 1 week. In clinical practice, however, such a delay may be difficult to observe. In order to explore the safety of a more rapid switch from TCA to MAOI therapy, we survey members of our department (Columbia University) as to their experience with different methods of switching patients from TCAs to MAOIs. Thirty-three respondents reported having switched an estimated 432 patients over the course of 3 years, with 178 patients switched within 4 days of discontinuing TCA therapy, including 63 who had the MAOI added while still being tapered from the TCA. More experienced psychiatrists tended to be less conservative, some using time intervals of 4 days or less. No adverse reactions were reported, including hypertensive and hyperpyrexic crises. This retrospective survey and an accompanying review of the literature suggest that the recommended drug-free interval of a week or more when switching patients from TCAs to MAOIs may be overly conservative.
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The role of substantia nigra (SN) in the development of kindling was investigated. Microinjection of gamma-vinyl gamma-aminobutyric acid (GVG), a gamma-aminobutyric acid (GABA) transaminase inhibitor, into the SN bilaterally retarded kindling development by 77%. GVG injected dorsal to the SN did not alter the kindling rate. By contrast, lesions of the SN, whether by thermocoagulation or by microinjected neurotoxin, N-methyl-D,L-aspartate, facilitated kindling development by 27-44%. Thermocoagulative lesions dorsal to the SN did not affect the rate of kindling development. Thus these two manipulations, each presumed to suppress the activity of the SN, resulted in opposite effects on kindling development. We interpret the pharmacologic findings to indicate that the intact SN can powerfully facilitate kindling development. However, the SN is not vital for kindling development, since kindling can be established after destruction of a considerable portion of SN. Whether the increased rate of kindling development following SN lesions is due solely to the absence of SN remains unclear.
We examined 3 different methods of brainstem lesioning to assess their propensities to evoke seizures in the early postoperative period. Lesioning by electrolysis or microinjection of the neurotoxin, N-methyl-D,L-aspartate, caused seizures, but lesioning by thermocoagulation (radiofrequency current) did not. In paradigms in which postoperative lesion-induced seizures could confound interpretation of experimental results, the thermocoagulative method offers an important advantage.
The authors describe the design and reliability of a rating scale that measures aggressive behaviors in adults and children. On the Overt Aggression Scale (OAS), aggression is divided into four categories: verbal aggression, physical aggression against objects, physical aggression against self, and physical aggression against others. In addition, specific interventions related to each aggressive event can be recorded on the OAS. The clinical and research applications of this scale are discussed.
As part of a pilot study to assess the efficacy of propranolol in the treatment of aggression in psychiatric patients, drug interactions of propranolol with other agents were estimated by blood level monitoring. In the two patients taking a standard oral dose of thioridazine, the addition of propranolol caused a threefold and fivefold increase of plasma thioridazine levels, which placed them in a potentially toxic range. Although neither patient exhibited a toxic effect, these levels may be associated with an increased risk of thioridazine-induced irreversible pigmentary retinopathy, cardiac arrhythmias, and tardive dyskinesia. The authors suggest precautionary monitoring of thioridazine plasma and other relevant levels and clinical assessments when thioridazine and propranolol are used in combination.
Chronic pain in the perineum is a difficult neurosurgical problem. This article evaluates the effectiveness of sacrococcygeal rhizotomy in 28 patients who had cancer-related pain or coccydynia, underwent rhizotomy, and were followed for an average of 3 years. Good pain relief was obtained in 53% (10 of 19 patients) with malignant pain, as opposed to 22% (2 of 9 patients) with nonmalignant pain. Sacral rhizotomy is a reasonable treatment for cancer-related perineal pain, but it is ineffective for coccydynia and other benign perineal pain problems.
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Eighty-one cases of mechanical small bowel obstruction were seen at our hospital in the three year period 1978 to 1980. Four (5%) were due to gallstone ileus, three of them in women. All four patients were more than 75 years of age. Because most patients with biliary-enteric fistulas and gallstone ileus are elderly and in poor general condition, simple removal of the obstruction gallstone is usually adequate, but interval cholecystectomy is recommended in patients with a long life expectancy, because recurrence of calculi and symptoms increases with time.