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Biomedical subjects

R E Harbaugh

Publications and source records attributed to R E Harbaugh.

At least 19 recordsLinked to original sources
PubMed1992

Cortical biopsy in Alzheimer's disease: diagnostic accuracy and neurochemical, neuropathological, and cognitive correlations. Intraventricular Bethanecol Study Group.

Neurochemical assessments were performed on biopsy samples taken from the right frontal lobe of patients diagnosed with Alzheimer's disease (AD), before the implantation of a ventricular catheter and pump assembly for the infusion of bethanechol chloride as an experimental therapy. The pathologically diagnosed patients with AD (n = 35; mean age, 67 +/- 1.5 yr) were compared with a group of samples from normal age-equivalent autopsied controls (n = 22; mean age, 68 +/- 2 yr) and autopsied AD brains (n = 11; mean age, 73 +/- 2 yr). Samples were assayed for choline acetyltransferase (ChAT), acetylcholinesterase, binding to [3H]quinuclidinyl benzilate as an index of total muscarinic cholinergic binding, and [3H]pirenzepine binding as an index of M1 cholinergic receptor subtype binding. Mean levels of ChAT activity were decreased in the biopsied patients to 36% of age-matched autopsied controls. The loss of ChAT activity correlated significantly with the Mini-Mental State Examination, an index of global cognitive function. Mean ChAT activity in autopsied AD cortex was further decreased compared with controls, indicating continuous decline through the course of the disease. Acetylcholinesterase followed a similar, less dramatic decline. No differences were found in [3H]quinuclidinyl benzilate binding or [3H]pirenzepine binding between biopsied and autopsied controls. Neuritic plaque counts did not correlate with either the Mini-Mental State Examination or ChAT activity in the biopsy specimens.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholinesterase↗
PubMed1992

Results of routine ventriculostomy with external ventricular drainage for acute hydrocephalus following subarachnoid haemorrhage.

We reviewed the results of ventriculostomy with external ventricular drainage in patients with acute hydrocephalus complicating subarachnoid haemorrhage. Of 194 consecutive patients with subarachnoid haemorrhage admitted during the past eight years, 52 (27%) developed hydrocephalus within 72 hours of the ictus. Patients with acute hydrocephalus were in grades III to V (Hunt and Hess) at the time of evaluation and all patients with hydrocephalus underwent ventriculostomy within 24 hours of diagnosis. Twenty-six patients improved within 24 hours of cerebrospinal fluid drainage and 17 of these patients underwent surgery, nine of whom did well (Glasgow Outcome Scale 1 and 2). All 18 patients who did not improve within this period, including one who worsened, died. In eight patients the response to ventriculostomy was considered as undetermined, because of the proximity of the drain insertion to a definitive surgical procedure, and all of them had an excellent outcome (Glasgow Outcome Scale 1). Of 32 patients in grades IV and V, 17 did not improve and all of them died. Eight of the 15 patients in these grades, who were in the improved or undetermined categories, did well. Five patients (10%) developed meningitis. All patients with this complication had drainage for more than four days. Seven patients (14%) had a rebleed during the drainage. All except one patient with a rebleed had no surgery or delayed surgery and in six of them recurrent haemorrhages occurred after more than 24 hours of drainage. We conclude that routine ventriculostomy with external ventricular drainage should be considered for all patients with altered sensorium and acute hydrocephalus following subarachnoid haemorrhage.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Three-dimensional computerized tomography angiography in the diagnosis of cerebrovascular disease.

Computer-generated three-dimensional reconstruction of the intracranial vascular system obtained by contrast-enhanced computerized tomography (CT) has been used in the diagnosis of 20 patients with known or suspected intracranial cerebrovascular disease. This technique allows visualization of the intracranial vasculature without exposing patients to the risks associated with intra-arterial angiography. The color prints and videotape images generated have been used to diagnose the presence of intracranial aneurysms, arteriovenous malformations, and venous angiomas. They have also been used to rule out structural abnormalities in patients with suspected intracranial vascular pathology and to screen patients with a strong family history of intracranial aneurysm. In 11 patients who underwent both three-dimensional CT angiography and intra-arterial angiography, the diagnostic correlation was 100%. No complications from the procedures or from incorrect diagnosis have been encountered. Although this technique requires further development and clinical evaluation, the authors' early experience with three-dimensional CT angiography suggests that this may become a valuable tool in the diagnosis of patients with cerebrovascular disease.

Adolescent↗
PubMed1991

Acute effects of a pedicled omental graft on cold-induced brain oedema in cats.

When used as a prophylactic measure and in chronic experiments, omental transposition has been shown to reduce ischaemic and traumatic oedema in the spinal cord and ischaemic oedema in the brain. We designed this experiment to evaluate the acute effects of a pedicled omental graft on cold-induced brain oedema in cats. Focal oedema was induced in the left frontoparietal region of the brain of nine anaesthetized cats. In five cats, a laparotomy was done and a pedicled omental graft was placed on the lesioned left hemisphere immediately after the cold lesion was made. All cats were sacrificed 72 hours later, and the water content of the white matter was determined in the lesioned and the normal hemispheres. The mean water content of the lesioned hemisphere of the treated group of animals was not significantly different from that of the control group. We conclude that a pedicled omental graft failed to reduce vasogenic oedema in an acute model and probably has no role in the acute management of brain oedema.

Animals↗
PubMed1991

Neurosurgical complications after intranasal ethmoidectomy.

Intranasal ethmoidectomy is a common otolaryngological procedure. Despite the potential for serious intracranial complications, there is a paucity of reports describing the neurosurgical complications of the procedure. Two patients with intracranial complications of intranasal ethmoidectomy, and the relevant medical literature, are reviewed. The anatomy of the ethmoid air cells and their relation to the intracranial cavity are described. The importance of definitive, emergent repair with attention to the potential for vascular injury is discussed.

Aged↗
PubMed1989

Anticonvulsant activity of the glial GABA uptake inhibitor, THAO, in chemical seizures.

The antiseizure activity of the glia-selective GABA uptake inhibitor, 5,6,7,8-tetrahydro-4H-isoxazolo[4,5-c]azepin-3-ol (THAO), was evaluated in rats in models of acute chemoconvulsion. In these experiments, intracerebroventricular administration of the drug 30 min prior to testing in doses between 100-750 micrograms provided protection against maximal pentylenetetrazol seizures and increased the latency to isonicotinic acid hydrazide seizures. Pentylenetetrazol seizure thresholds, in contrast, were not significantly elevated. The ability of THAO to suppress tonic but not generalized minor seizures suggests that it may block seizure spread.

Animals↗
PubMed1989

Nerve growth factor as a potential treatment in Alzheimer's disease.

An adequate rationale for considering the use of NGF in the treatment of AD exists. Much basic work needs to be done prior to any clinical trials in order to design an ethically and scientifically sound study. The potential use of NGF in patients with AD is a very exciting possibility; enthusiasm should not, however, lead to poorly designed premature clinical trials which are unlikely to provide definitive answers as to the effectiveness of such treatment.

Alzheimer Disease↗
PubMed1989

The spectrum of imaging and neuropsychological findings in Pick's disease.

To seek improved methods for the diagnosis of Pick's disease, we reviewed imaging studies of four women and two men (ages 48 to 65 years at onset) and psychometric testing of three of them with autopsy or biopsy-proved Pick's. The presence of Pick bodies was required for the diagnosis. Seven patients with biopsy-proved Alzheimer's disease served as a comparison group. In the Pick's patients, CT in five of six showed marked frontal pole or temporal pole atrophy, which clearly differed from the pattern of cerebral atrophy seen in the Alzheimer's patients. Psychometric testing showed performance patterns that tended to differ from those of the Alzheimer's patients in that recent memory was relatively preserved despite marked impairment of executive functions. The distinctive psychometric pattern in the Pick's patients was evanescent, however. Thus, there were imaging and psychometric findings of potential diagnostic value for Pick's disease, but, for different reasons, they were imperfect.

Aged↗
PubMed1989

Administration of intravenous urea and normal saline for the treatment of hyponatremia in neurosurgical patients.

Hyponatremia frequently complicates the care of neurosurgical patients and requires prompt effective therapy. These patients commonly fulfill the laboratory criteria of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) or cerebral salt wasting; the classification depends on the volume status of the patient. The authors have been dissatisfied with the standard therapy of fluid restriction for the critically ill neurosurgical patient because of 1) slow rates of sodium correction; 2) poor applicability in patients requiring multiple intravenous medications and/or nutritional support; and 3) possible dangers of inducing or enhancing cerebral ischemia in patients who already may be fluid-depleted. Reported successes in the treatment of hyponatremia due to SIADH by administration of urea and normal saline led to the authors' routine use of this therapy for hyponatremic neurosurgical patients. A retrospective review of an 18-month period revealed 48 patients (3% of all neurosurgical inpatients) with hyponatremia from various causes who received 62 treatments of urea and normal saline. Treatment consisted of 40 gm urea dissolved in 100 to 150 ml normal saline as an intravenous drip every 8 hours and an intravenous infusion of normal saline at 60 to 100 ml/hr for 1 to 2 days. The mean pretreatment serum sodium level (+/- standard deviation) was 130 +/- 3 mmol/liter (range from 119 to 134 mmol/liter). There was a significant mean posttreatment elevation to 138 +/- 4 mmol/liter (range 129 to 148 mmol/liter) (p less than 0.001, Student's t-test). Average daily fluid intake and output on treatment days were 2719 +/- 912 and 2892 +/- 1357 ml, respectively. There were no treatment complications in this group. It is concluded that urea and saline administration results in a rapid, safe, and effective correction of hyponatremia, making this method superior to fluid restriction in many neurosurgical patients.

Blood Urea Nitrogen↗
PubMed1989

Intracerebroventricular bethanechol chloride infusion in Alzheimer's disease. Results of a collaborative double-blind study.

The use of intracerebroventricular bethanechol chloride infusion in patients with Alzheimer's disease was first reported in 1984. An initial trial in four patients demonstrated the feasibility of this approach for cholinergic drug delivery to the brain, but objective improvement in cognitive function was not documented. A collaborative placebo-controlled double-blind crossover study has now been carried out in 49 patients with biopsy-documented Alzheimer's disease. The results demonstrate a statistical improvement in Mini-Mental State scores and significantly slower performance on Trails A testing during drug infusion. Other neuropsychological test scores were not similarly affected. The degree of improvement was not sufficient to justify further treatment of Alzheimer's disease patients by intracerebroventricular infusion of bethanechol chloride. The drug delivery system used in the study was well tolerated, with two irreversible complications in more than 50,000 patient days.

Alzheimer Disease↗
PubMed1988

Intracerebroventricular bethanechol chloride administration in Alzheimer's disease.

In June 1983 we began evaluating intracerebroventricular (ICV) cholinergic drug infusion in patients with biopsy-documented Alzheimer's disease (AD). An initial trial in four patients showed this treatment approach to be feasible, but objective improvement in cognitive or social function was not documented. A double-blind, placebo-controlled crossover study involving a larger number of patients has since been done. The results of this study, presented here, document a statistically significant improvement in some neuropsychological test results during periods of drug infusion. However, the degree of improvement is not sufficient to justify further treatment with the presently available drug, bethanechol chloride.

Aged↗
PubMed1988

Encephalomeningocele presenting with spontaneous cerebrospinal fluid rhinorrhea in an elderly man: case report.

The case of a patient with spontaneous cerebrospinal fluid (CSF) rhinorrhea from an intranasal encephalomeningocele is presented. The case is unusual in that the patient was entirely asymptomatic until the age of 65, when copious CSF rhinorrhea developed without trauma or operation as an inciting event. The pertinent literature is reviewed, and no identical case has been found.

Aged↗
PubMed1988

Use of implantable pumps for central nervous system drug infusions to treat neurological disease.

Increasing knowledge of the neurochemical aspects of central nervous system function raises the possibility of treating neurological disease by the appropriate manipulation of neurotransmitters, neuromodulators, and neurohormones. Clinical application of this knowledge has been inhibited, however, by long-standing problems with drug delivery to the central nervous system (CNS). The availability of implantable drug infusion pumps and stereotactic catheter placement techniques may overcome many of these problems. The problems of drug delivery to the brain and the present and potential uses of implantable drug pumps for neurological disease are discussed. In addition, the relationship between CNS drug infusion and neural tissue transplantation is briefly reviewed.

Brain Neoplasms↗
PubMed1987

External ventricular drainage for initial treatment of neonatal posthemorrhagic hydrocephalus: surgical and neurodevelopmental outcome.

Thirty-seven infants were treated for posthemorrhagic hydrocephalus (PHH) with external ventricular drainage (EVD) in 1977-1985. The mean age at EVD placement was 13 days; the mean duration of drainage was 21 days, and an average of 1.8 drains was used per patient. Complications were apnea (10%), hemorrhage (8%) and ventriculitis (6%). Ten infants died from pulmonary disease unrelated to the surgery. Thirty-two percent of the survivors did not require a permanent shunt. Neurodevelopmental outcome was evaluated at a mean age of 38 months. Eighteen of the twenty-seven survivors (67%) had normal cognitive function, 3 had borderline and 6 (22%) had moderate to profound mental retardation. Nine of the children (33%) had a normal neuromuscular exam. One child had mild, 11 had moderate and 6 had severe cerebral palsy. Four children had serious visual impairment. The worst outcomes were in the children with parenchymal or large intraventricular hemorrhages.

Cerebral Hemorrhage↗
PubMed1987

Intracerebroventricular cholinergic drug administration in Alzheimer's disease: preliminary results of a double-blind study.

In June 1983, we began evaluating intracerebroventricular (ICV) cholinergic drug infusion in patients with biopsy-documented Alzheimer's disease (AD). An initial trial in four patients showed this treatment approach to be feasible, but objective improvement in cognitive or social function was not documented (Harbaugh et al., 1984; Harbaugh, 1986). A double-blind, placebo-controlled crossover study involving a larger number of patients has since been done. The results of this study, presented here, document a statistically significant improvement in some cognitive test results during periods of drug infusion. However, the clinical applicability of this treatment approach is still questionable. A collaborative, double-blind study evaluating activities of daily living and cognitive test results during drug and placebo infusion is presently underway and should better define the safety and efficacy of this treatment approach for patients with AD.

Aged↗