Search PubMed⌕ Search

Biomedical subjects

D H Lowenstein

Publications and source records attributed to D H Lowenstein.

At least 73 records · Page 4Linked to original sources
PubMed1990

The pattern of 72-kDa heat shock protein-like immunoreactivity in the rat brain following flurothyl-induced status epilepticus.

The inducible 72-kDa heat shock protein (HSP72) is a highly conserved stress protein that is expressed in CNS cells and may play a role in protection from neural injury. We used a monoclonal antibody to HSP72 and immunocytochemistry to localize HSP72 in the rat brain 24 h following either 30 or 60 min of flurothyl-induced status epilepticus. Sprague-Dawley rats were anesthetized with halothane, paralyzed, and ventilated, and remained normotensive and well oxygenated for the duration of the seizures. Seizure activity was quantified via analysis of the scalp EEG pattern. HSP72-like immunoreactivity (HSP72-LI) was induced in specific brain regions in a graded fashion that correlated, in part, with the duration and degree of seizure activity. Milder seizures produced HSP72-LI limited to layers 2 and 3 of frontoparietal cortex, dentate hilus cells, and CA3 pyramidal neurons. More extensive seizures led to HSP72-LI in layers 2, 3 and 5 of frontoparietal and visual cortex, dentate hilus cells, CA1 and CA3 pyramidal neurons, and certain thalamic and amygdaloid nuclei. These are similar to many, but not all, of the brain regions known to be injured with this model. No HSP72-LI was observed in sham-treated controls or flurothyl-treated animals whose seizures were controlled with pentobarbital. HSP72-LI thus localizes to certain regions of seizure-induced injury, and may provide a sensitive method of detecting neuronal 'stress' or injury relatively soon after status epilepticus. Whether or not HSP72 synthesis plays a protective role in the pathogenesis of seizures, or is only a marker for cell injury, remains to be determined.

Animals↗
PubMed1990

Three hamster species with different scrapie incubation times and neuropathological features encode distinct prion proteins.

Given the critical role of the prion protein (PrP) in the transmission and pathogenesis of experimental scrapie, we investigated the PrP gene and its protein products in three hamster species, Chinese (CHa), Armenian (AHa), and Syrian (SHa), each of which were found to have distinctive scrapie incubation times. Passaging studies demonstrated that the host species, and not the source of scrapie prions, determined the incubation time for each species, and histochemical studies of hamsters with clinical signs of scrapie revealed characteristic patterns of neuropathology. Northern (RNA) analysis showed the size of PrP mRNA from CHa, AHa, and SHa hamsters to be 2.5, 2.4, and 2.1 kilobases, respectively. Immunoblotting demonstrated that the PrP isoforms were of similar size (33 to 35 kilodaltons); however, the monoclonal antibody 13A5 raised against SHa PrP did not react with the CHa or AHa PrP molecules. Comparison of the three predicted amino acid sequences revealed that each is distinct. Furthermore, differences within the PrP open reading frame that uniquely distinguish the three hamster species are within a hydrophilic segment of 11 amino acids that includes polymorphisms linked to scrapie incubation times in inbred mice and an inherited prion disease of humans. Single polymorphisms in this region correlate with the presence or absence of amyloid plaques for a given hamster species or mouse inbred strain. Our findings demonstrate distinctive molecular, pathological, and clinical characteristics of scrapie in three related species and are consistent with the hypothesis that molecular properties of the host PrP play a pivotal role in determining the incubation time and neuropathological features of scrapie.

Animals↗
PubMed1990

Neurologic consequences of cocaine use.

Neurologic consequences of cocaine use frequently present as medical emergencies in the form of stroke, repeated seizures, encephalopathy, acute headache, and unusual transient neurological deficits. The often fatal or disabling neurologic syndromes have only recently been recognized but are now well documented. Cocaine use is a significant cause of stroke in young adults, and the full, long-term ramifications of maternal cocaine use on the fetus will not be known for years to come. Unfortunately, there is not effective treatment other than abstinence, and our understanding of the pathophysiology of cocaine-associated neurologic illness remains limited.

Animals↗
PubMed1989

Cerebral infarctions and transient neurologic deficits associated with acquired immunodeficiency syndrome.

PURPOSE: Little information is available concerning the clinical importance of cerebral infarction in patients with acquired immunodeficiency syndrome (AIDS). The purpose of this retrospective study was two-fold: (1) to determine the frequency and clinical characteristics of cerebral infarction and transient neurologic deficits (TNDs) among patients with AIDS; and (2) to identify specific patient subgroups at risk for such complications and whether there were underlying associated diseases requiring specific therapy. PATIENTS AND METHODS: Neurology inpatient and consult service records, neuropathology reports, and the University of California, San Francisco, AIDS computerized registry were used in identifying study cases. Information on demographic background, associated clinical diagnoses, presenting neurologic symptoms and signs, laboratory results, pathologic findings, and clinical follow-up was obtained from each patient's medical record. RESULTS: Twenty-five patients with AIDS (mean age, 38) having clinical or pathologic findings suggestive of focal cerebral ischemia or infarction were identified. Ten patients had non-hemorrhagic cerebral infarctions, 13 had acute TNDs, and two had both. Cerebral infarction was associated with central nervous system (CNS) infections (cryptococcus, four; tuberculosis, one; zoster vasculitis, one) and cardiogenic embolism (one). TNDs were associated with toxoplasmosis (four), cerebral infarction (two), cryptococcal meningitis (one), vasculitis (one), and CNS Kaposi's sarcoma (one). A presumptive cause was absent in five cases of cerebral infarction and eight of TND. All five patients with pathologically proven macroscopic cerebral infarcts were diagnosed clinically before death. CONCLUSIONS: We conclude the following: (1) AIDS patients, especially given their young age, appear to be increased risk for cerebral infarction and TND. (2) Cerebral infarction and TND may be the initial presentation of AIDS. (3) TND and cerebral infarction often signify treatable CNS infection among AIDS patients. (4) The causes of AIDS-related cerebral infarction and TND are unknown in many cases.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Placebo-controlled trial of intravenous diphenylhydantoin for short-term treatment of alcohol withdrawal seizures.

PURPOSE: Despite conflicting experimental and clinical evidence, diphenylhydantoin continues to be used for the treatment of alcohol withdrawal seizures in emergency departments and alcohol detoxification centers. Our goal was to evaluate the effectiveness of intravenous diphenylhydantoin for prevention of alcohol withdrawal seizures in high-risk patients using a prospective, randomized, double-blind, placebo-controlled study design. PATIENTS AND METHODS: Ninety alcoholic patients, enrolled within six hours of the initial alcohol-related seizure in a withdrawal episode, were randomly assigned to treatment with intravenous diphenylhydantoin (1,000 mg) or placebo. Seventy-one patients had a history of seizures during prior alcohol withdrawal episodes. Patients with a history of seizures unrelated to alcohol withdrawal were excluded. Drugs known to affect the seizure threshold or demonstrating cross-tolerance with alcohol were withheld. For each patient, the study endpoint was either (1) seizure recurrence or (2) a minimum 12-hour seizure-free observation period after completion of the study drug infusion. RESULTS: During the postinfusion observation period, six of 45 diphenylhydantoin-treated patients and six of 45 placebo-treated patients experienced at least one recurrent seizure. Equivalent diphenylhydantoin serum levels were measured in patients with and without subsequent seizures. There was no statistically significant difference between the response rates for the two treatments (p greater than 0.05). The 95% confidence interval for the difference in response probabilities was -14.0%, 14%. CONCLUSION: When administered to non-epileptic patients within six hours of the onset of alcohol withdrawal seizures, intravenous diphenylhydantoin failed to show a significant benefit over placebo in the prevention of subsequent seizures. We suggest that the well-documented risks of intravenous diphenylhydantoin therapy outweigh the potential benefit in the short-term treatment of alcohol withdrawal seizures.

Adult↗
PubMed1989

Controlled trial of botulinum toxin injections in the treatment of spasmodic torticollis.

We administered local injections of botulinum toxin to 20 patients with torticollis in a blinded, placebo-controlled study. Each patient received four sets of injections: three different doses of botulinum toxin and one placebo. The order of the sessions was random and unknown to the patients. Sixteen of the patients (80%) reported subjective improvement to at least one dose of botulinum toxin; 11 (55%) reported substantial improvement. No objective benefit was documented. Side effects were minor and transient, although dysphagia occurred in four. Some patients reported that the effect waned despite persistent relaxation or even flaccidity of previously overactive muscles, suggesting a change in the pattern of muscle activity after botulinum toxin injections.

Adult↗
PubMed1989

Thalamomesencephalic strokes after cocaine abuse.

Three young patients developed strokes of rostral midbrain and thalamus shortly following cocaine abuse. Two had infarctions and one had a hemorrhage, but none had clear risk factors other than cocaine for this relatively uncommon type of stroke. Toxicologic analysis confirmed isolated cocaine use in each patient. In the two cases of infarction studied angiographically, one had normal findings and the other had focal narrowing of the P1 segments of the posterior cerebral arteries bilaterally. Since the P1 segment has a uniquely sparse perivascular sympathetic supply, we suggest that direct adrenergic-mediated vasoconstriction is not critical to the production of cocaine-associated stroke.

Adult↗
PubMed1989

Seizures associated with recreational drug abuse.

We retrospectively identified 49 cases of recreational drug-induced seizures in 47 patients seen at the San Francisco General Hospital between 1975 and 1987. Most patients experienced a single generalized tonic-clonic seizure associated with acute drug intoxication, but 7 patients had multiple seizures and 2 patients developed status epilepticus. The recreational drugs implicated were cocaine (32 cases), amphetamine (11), heroin (7), and phencyclidine (4). A combination of drugs was responsible in 11 cases. Seizures occurred independent of the route of administration, and occurred in both first-time and chronic abusers. Ten patients (21%) reported having had prior seizures, all with a close temporal association with drug abuse. Other than 1 patient who developed prolonged status epilepticus that caused a fixed neurologic deficit, most patients had no obvious short-term neurologic sequelae.

Adult↗
PubMed1988

Neuromuscular effects distant from the site of botulinum neurotoxin injection.

We assessed the severity and temporal profile of distant neuromuscular effects from a single dose (280 units) of botulinum neurotoxin injected into neck muscles for torticollis. We performed single-fiber EMG studies on the biceps brachii of six patients to measure jitter (20 pairs) and fiber density on the initial treatment day and then again, at least once more, after 2 to 12 weeks. No patient developed weakness beyond the neck muscles or decrement of the biceps response to repetitive 3-Hz nerve stimulation. Between the baseline and the last follow-up study, the average of mean MCD increased from 29 microseconds to 38 microseconds (31%). Mean fiber density increased concurrently or earlier from 1.35 to 1.79 (33%). There were no electrophysiologic signs of presynaptic blockade, even at 2 and 4 weeks. The effects we observed are compatible with stimulation of terminal sprouting by the neurotoxin, without significant presynaptic inhibition of acetylcholine release. We therefore believe that higher dosages of the neurotoxin may be used if clinically indicated.

Adult↗
PubMed1988

Barbiturate anesthesia in the treatment of status epilepticus: clinical experience with 14 patients.

We report our experience using barbiturate anesthesia for the treatment of refractory status epilepticus. Following a retrospective review of eight patients treated with a variety of barbiturates and dosing regimens, we established a specific protocol employing pentobarbital and evaluated it prospectively in six patients. Among the 14 patients, intravenous barbiturates, when administered with a loading dose followed by continuous infusion, were uniformly effective in aborting seizures and producing a burst-suppression EEG pattern. Other than the pupillary light reflex, most patients lost all brainstem reflexes and motor responses during therapy. Barbiturate-induced hypotension was observed in 9 of the 14 patients, and required treatment with pressors in seven cases. Three patients died early as a consequence of their underlying illness, while three others died late for reasons unrelated to the status itself or to anticonvulsant therapy. The time to recovery of function following anesthesia varied highly, spanning hours to days for return of motor function and days to weeks for cognition. Of the eight survivors, four were left with mild cognitive deficits, one returned to his baseline dementia, and three had residual encephalopathies (severe in two). We conclude that barbiturate anesthesia is an extremely effective therapy for refractory seizures. However, its use necessitates recognition of untoward cardiovascular responses and prolonged intensive care.

Anesthesia↗
PubMed1988

The clinical course of spasmodic torticollis.

Among 24 of 36 patients with idiopathic spasmodic torticollis referred to one of us over a 10-year period, who were followed up for more than 1 year, we defined three outcome groups. Three patients (13%) underwent complete or almost complete remission at a median of 3.0 years into the illness. Eight patients (33%) had partial remissions, which tended to occur somewhat later than the first group. The remaining 13 patients had no significant improvement in their disease; they were more likely to be older at the onset of the illness, develop constant rather than intermittent neck deviation, and have a "geste antagonistique." As a whole, the study population was exposed to a wide variety of therapeutic interventions that had little, if any, obvious clinical effect.

Adolescent↗
PubMed1988

Primary cerebral angiosarcoma. Case report.

A 65-year-old man with a history of exposure to industrial solvents developed a primary cerebral angiosarcoma in the left posterior parieto-occipital lobe. The tumor had features typical of angiosarcoma on light and electron microscopy, immunohistochemical evidence of factor VIII-related antigen produced in tumor cells, and a high labeling index with bromodeoxyuridine. The relationship of angiosarcoma to toxins and viruses is discussed.

Aged↗
PubMed1987

Cerebral ptosis with contralateral arteriovenous malformation: a report of two cases.

We describe two patients with chronic unilateral ptosis and contralateral hemispheric arteriovenous malformations. Both patients were brought to our attention after a subacute or acute neurological deterioration. Analysis of prior photographs showed the ptosis progressed up to the time of presentation and significantly resolved following surgical removal of the arteriovenous malformation. The partially reversible and chronic nature of the ptosis in these two patients represents a particularly unusual forms of cerebral ptosis.

Adolescent↗
PubMed1987

Acute neurologic and psychiatric complications associated with cocaine abuse.

This report reviewed 996 emergency room visits and 279 hospital admissions of patients with complications of cocaine abuse seen at the San Francisco General Hospital between 1979 and 1986. In 143 cases, acute neurologic or psychiatric symptoms were the primary complaint, and case-notes provided sufficient detail for analysis. The major neurologic complications included one or more seizures (n = 29), focal neurologic symptoms or signs (12), headache (10), and transient loss of consciousness (six). Psychiatric disturbances included agitation, anxiety, or depression (33), psychosis and paranoia (24), and suicidal ideation (18). The most serious consequences were found in patients with prolonged seizures or strokes, those who jumped out of buildings, and those who attempted suicide by overdosing with other drugs. There was no correlation between the appearance of complications and the reported route of administration, the amount of cocaine used, or prior experience with cocaine. The number of patients who are seeking hospital attention for these or related complaints appears to be rising substantially. Cocaine abuse, regardless of the use pattern, is associated with a variety of potentially severe neurologic and psychiatric complications.

Adult↗
PubMed1979

Combining segmental systolic pressures and plethysmography to diagnose arterial occlusive disease of the legs.

Computer-assisted analysis of the data from SLP and PVR study of the legs with angiographically documented arterial occlusive disease, projected against a background of normal limbs, was used to assess the diagnostic value of each study, including its individual variables, as well as their varied combinations. The accuracy of both SLP and PVR interpretation was significantly improved by standarization against brachial values, but even with the aid of superimposed physician interpretation, each only reached 86 per cent when cases with multilevel occlusive disease were included. The combination of these two studies, which compensate for each other's limitations in several respects, achieved an overall accuracy of 97 per cent, with no errors observed in diagnosing either normal limbs or those with isolated occlusive disease. Objective diagnostic criteria for both SLP and PVR interpreatation are presented in algorithmic form.

Arterial Occlusive Diseases↗