Inhibitory influence of the dorsal nucleus of the lateral lemniscus on binaural responses in the rat's inferior colliculus.

The contribution of the dorsal nucleus of the lateral lemniscus (DNLL) to binaural processing was examined by recording single-unit activity in the rat's inferior colliculus before, during, and after a reversible block of the excitatory activity in DNLL by local injection of kynurenic acid. Recordings were made from the central nucleus of the inferior colliculus with glass micropipettes filled with 3 M sodium acetate. Kynurenic acid (2 mM in Locke's solution) was injected into the DNLL through one side of a double-barreled glass pipette. The other side of the pipette was filled with Locke's solution for making control injections and recording neural activity. Pressure injection of 0.7-2.0 microliter of kynurenic acid resulted in the complete cessation of tone-evoked responses in DNLL for periods of 45 min to 1 hr. Tone bursts were delivered separately to the two ears through headphones fitted to the external auditory meatus. Binaural responses in the inferior colliculus were determined by comparing the effects of monaural and binaural stimulation. Attention was focused on neurons that were excited by contralateral stimulation and inhibited by ipsilateral stimulation. Interaural intensity difference (IID) functions were generated by holding contralateral sound pressure constant at 10 dB above threshold while increasing ipsilateral sound pressure level. Prior to kynurenic acid injection, ipsilateral stimulation caused a pronounced suppression of contralaterally evoked single-unit activity. Unilateral injection of kynurenic acid into DNLL reduced the strength of binaural suppression in the contralateral inferior colliculus. In every cell tested, the IID curve in inferior colliculus was shifted following contralateral DNLL injection. The IID curve returned to normal after recovery of neural activity in DNLL. In contrast, no effect was seen in the inferior colliculus ipsilateral to the kynurenic acid injection. The injection of Locke's solution into DNLL had no effect on IID curves in the inferior colliculus. These data suggest that the DNLL plays a role in binaural processing through an inhibitory influence on responses in the contralateral inferior colliculus.


A multipotent EGF-responsive striatal embryonic progenitor cell produces neurons and astrocytes.

The mitogenic actions of epidermal growth factor (EGF) were examined in low-density, dissociated cultures of embryonic day 14 mouse striatal primordia, under serum-free defined conditions. EGF induced the proliferation of single progenitor cells that began to divide between 5 and 7 d in vitro, and after 13 d in vitro had formed a cluster of undifferentiated cells that expressed nestin, an intermediate filament present in neuroepithelial stem cells. In the continued presence of EGF, cells migrated from the proliferating core and differentiated into neurons and astrocytes. The actions of EGF were mimicked by the homolog transforming growth factor alpha (TGF alpha), but not by NGF, basic fibroblast growth factor, platelet-derived growth factor, or TGF beta. In EGF-generated cultures, cells with neuronal morphology contained immunoreactivity for GABA, substance P, and methionine-enkephalin, three neurotransmitters of the adult striatum. Amplification of embryonic day 14 striatal mRNA by using reverse transcription/PCR revealed mRNAs for EGF, TGF alpha, and the EGF receptor. These findings suggest that EGF and/or TGF alpha may act on a multipotent progenitor cell in the striatum to generate both neurons and astrocytes.


Clinical semiology of common cervicobrachial neuralgia. Data from 50 hospital cases.

Common cervicobrachial neuralgia is less frequent than sciatica and its aetiological profile is more varied: men and women are equally affected, triggering factors or previous history are less often found and patients with anxiety or depression are relatively numerous. Clinically, signs of C7 lesion are present in half the patients. Acroparesthesias are frequent and may be the initial signs. Nocturnal pain is present in 50% of the cases. Signs of neurological deficit are rare, except for abolition of a reflex. The association of cervicobrachial neuralgia with tendinitis of the upper limb or algodystrophy of the shoulder is too frequent to be fortuitous. Left to itself, the syndrome usually lasts several months and sometimes one year. Recurrences are rare. The most frequent sequela is a painful neck.


Cervicobrachial neuralgia: diagnostic problems in neurology.

A population of 205 patients hospitalized for evaluation of cervicobrachial pain was retrospectively studied. Four aetiological groups were individualized: common cervicobrachial neuralgia (CBN) due to nucleus pulposus herniation or spondylarthrosis (119 cases); inflammatory radicular lesion (39 cases); CBN reflecting lesions of the cervicobrachial plexus or the spine (23 cases) and pain of undetermined origin (22 cases). The semiological characteristics of these four groups are discussed.


Neurophysiological explorations in cervicobrachial neuralgia.

The various electrophysiological techniques which can be used in cervicobrachial neuralgia and their respective advantages and limitations are described. Beside the conventional electromyography and electrostimulation techniques, the indications for radicular motor and somesthetic evoked potentials are discussed.


Plain radiography in the evaluation of cervicobrachial neuralgia.

Standard radiography is indispensable to the initial evaluation of cervicobrachial neuralgia. Its main purpose is not to detect a nucleus pulposus herniation or a spondylarthrosis responsible for the neuralgia, but to exclude a possible malignancy. In some cases standard radiography points out to a less frequent cause, such as constitutional stenosis of intervertebral foramina not necessarily associated with a narrow vertebral canal.


CT, myelography and CT-myelography in the evaluation of common cervicobrachial neuralgia.

The CT technique used to explore intervertebral discs and foramina is described, as are the CT signs of nucleus pulposus (NP) herniation and cervical degenerative lesions. CT with intravenous contrast injection is the most efficient and easiest method to diagnose a radicular compression of discal or degenerative origin. The advent of high-resolution contrast CT will probably make obsolete the use of contrast media. CT measures the width of the vertebral canal, but it does not evaluate the repercussions on the spinal cord of compression caused by NP herniation or osteophytosis: only CT-myelography or, better, MRI can make this evaluation. Conventional CT scans are sometimes inadequate when exploration is hampered by superimposition of the shoulders (C6-C7 and more often C7-T1), when the scanner is of poor quality or when it is misused. Myelography and CT-myelography can then be utilized to resolve the problem posed by C7 or C8 cervicobrachial neuralgia (CBN). CT makes it possible to exclude most of the causes of non-discal CBN in the extradural spaces (e.g. bone tumour, neurinoma, vertebral vascular malformation, paravertebral expansive process, apical lung tumour). The search for an intradural cause (extra- or intramedullary tumour) rests on myelography, CT-myelography and MRI.


MRI and cervicobrachial neuralgia.

Recent improvements in magnetic resonance imaging techniques have altered our choices in the exploration of cervicobrachial neuralgia (CBN). The use of high-field machines, new acquisition sequences and paramagnetic contrast media has increased the sensitivity and specificity of the MRI method in the detection of degenerative lesions responsible for CBN. These new techniques are essentially based on gradient-echo sequences can be acquired in two or three dimensions, and each of them has its own advantages and drawbacks, but their performance is sufficient for MRI to be now considered a reliable and non-traumatic exploratory method for CBN. Performed after standard radiography, MRI tends to be the first-choice examination in the preoperative evaluation of cervical radiculopathies and myelopathies.


Treatment of cervicobrachial neuralgia in orthopaedic medicine.

Orthopaedic and physiotherapeutic treatments must necessarily complete the medicinal treatment of common cervicobrachial neuralgia. Rest in a posture that suppresses or attenuates the disc-nerve root conflict is mandatory. The use of physical agents (ultrasounds, short waves), rehabilitation, local injections, vertebral tractions and manipulations depends on the results of clinical examination. Every anatomico-clinical lesion detected has indications that guide the therapeutic approach. Close supervision of these treatments is indispensable to modify their rhythm and intensity or to stop them.


Results of surgical treatment for cervicobrachial neuralgia. A retrospective study of 122 patients with long-term follow-up.

Surgical nerve root decompression is rarely needed in the treatment of cervicobrachial neuralgia. In patients with prolonged and resistant pain or neurological deficits, or when signs of associated spinal cord suffering have been found, various surgical procedures can be used, but is most cases the disco-arthro-radicular conflict can be solved by the anterior approach with or without bone graft. This review of long-term résults in a series of 122 patients operated upon and re-examined more than 3 years later shows that the radicular symptoms were relieved in 95% of the cases. Evaluation of anatomical results did not reveal any instability or aggravation of discarthrosis at the site of surgery. However, in 30% of the cases disc degeneration was increased in the over- and underlying levels but without recurrence of clinical symptoms; 4% of the patients in this series were reoperated upon for this aggravated or de novo disc disease. The authors underline the importance of a thorough radioanatomical examination not only to decide whether or not a "soft hernia" or an arthrotic hypertrophy should be operated, but also to evaluate the extent of the decompressive operation to be performed.


Automated percutaneous nucleotomy in the treatment of cervicobrachial neuralgia due to disc herniation.

Forty-five patients suffering from cervicobrachial neuralgia resistant to medical treatment were treated by automated percutaneous nucleotomy according to the technique used by Onik et al. in the lumbar segment of the spine. Good results were obtained with this technique in 85% of the patients. This figure is similar to that reported for nucleorthesis without the risk of calcification mentioned in the literature.


The radiologist and common cervicobrachial neuralgia.

The neuroradiological methods used for the diagnosis of common cervicobrachial neuralgia are not the same in all medical centres and hospitals, one of the main reasons for this lack of unanimity being differences in organization and availability of equipment. However, the modern diagnostic approach should include magnetic resonance as first examination. MRI is the most informative and the least hazardous of all exploratory methods, and it detects or excludes a much greater number of causes than any other radiological technique. False-negative results, as well as late, incomplete or wrong diagnosis are therefore reduced to the minimum. False-positive results can be avoided by a good knowledge of the physiological incidence of uncodiscarthrosis with age.


Linear accelerator radiosurgery for arteriovenous malformations.

Between May, 1988, and August, 1991, 80 patients with arteriovenous malformations (AVM's) were treated radiosurgically at the University of Florida. A mean dose of 1650 cGy was directed to the periphery of the lesion, which almost always corresponded to the 80% isodose line. The mean lesion diameter was 23 mm. Seventy-six patients were treated with one isocenter. Angiography, performed at 1 year after radiosurgery in 41 of the 48 eligible patients, revealed an overall complete thrombosis rate of 39%. The 1-year thrombosis rate was highest in those patients with relatively small AVM's. Angiography was performed at 2 years posttreatment in 21 of the 25 eligible patients, demonstrating an overall complete thrombosis rate of 81%. This incidence did not correlate with lesion size: that is, large lesions (up to 35 mm in diameter) seemed just as likely to thrombose. Two patients (2.5%) experienced hemorrhage at some time after radiosurgical treatment, and both recovered. Two patients (2.5%) have sustained mild, but permanent, radiation-induced neurological complications.


Superselective intra-arterial infusion of papaverine for the treatment of cerebral vasospasm after subarachnoid hemorrhage.

This report describes the successful treatment of cerebral vasospasm after subarachnoid hemorrhage with superselective intra-arterial infusion of papaverine hydrochloride. Thirty-seven vascular territories in 10 patients with symptomatic vasospasm were treated according to the following protocol. Percutaneous transluminal angioplasty was performed in two steps. First, a silicone balloon was used for dilation of the internal carotid artery and the proximal portions of the middle cerebral artery. A silicone leak balloon or Tracker-18 catheter was then introduced into or just proximal to the site of vasospasm not accessible to the angioplasty balloon catheter for superselective infusion of 0.2% papaverine. Thirty-four of 37 vascular territories were successfully dilated, and eight of 10 patients showed improvement in neurological function after the procedure. There were no serious side effects due to infusion of papaverine. It is essential to infuse the papaverine just proximal to the spastic vessels in order to deliver sufficient concentration of drug, and infusion should be carried out as early as possible before the artery loses its ability to return to a normal luminal size. Superselective intraarterial infusion of papaverine is an alternative method of treatment for symptomatic vasospasm.


Treatment of cerebral vasospasm with intra-arterial papaverine.

Cerebral vasospasm continues to be the leading treatable cause of morbidity and mortality following aneurysmal subarachnoid hemorrhage. In this preliminary anecdotal series of 12 patients who were candidates for balloon angioplasty, vasospasm was treated instead with intra-arterial papaverine. Eight patients had marked angiographic reversal of the arterial narrowing following papaverine infusion, four of whom showed dramatic reversal of profound neurological deficits. Two patients deteriorated clinically 5 days after the initially successful papaverine infusions. In both, repeat angiography demonstrated severe recurrent vasospasm, which was partially reversed with a second intra-arterial papaverine treatment. Two patients developed focal neurological deficits during papaverine infusion, which resolved spontaneously over several hours after cessation of the intra-arterial infusion. Arterial narrowing in the posterior circulation and middle cerebral artery distribution appeared to be more responsive to papaverine infusion than was spasm in the anterior cerebral arteries. The infusion of 300 mg of papaverine over 1 hour seemed to be an adequate and safe dose to effect these angiographic and clinical improvements.


The treatment of associated intracranial aneurysms and arteriovenous malformations.

Cerebral arterial aneurysm associated with arteriovenous malformation (AVM) has been described with a variable incidence, averaging 10% of AVM cases. The present series includes 39 patients with this association, derived from a total of 400 patients with AVM's evaluated and treated since 1970. The aneurysms are classified into four major groups, each carrying particular therapeutic implications. Optimum treatment of these lesions is based in part on a knowledge of the hemodynamic alterations associated with the AVM's. In most of these cases, the symptomatic lesion was treated first; occasionally, when feasible, both lesions were treated during the same operation. All patients had some form of treatment, either surgical or endovascular, directed to at least one of the two types of lesions. All symptomatic lesions were treated and all ruptured aneurysms were obliterated. There were no deaths in this series.


Transpedicular screw-rod fixation of the lumbar spine: operative technique and outcome in 104 cases.

A total of 104 patients underwent transpedicular spinal instrumentation using the Cotrel-Dubousset (71 cases) or the Texas Scottish Rite Hospital (33) screw-rod system. Surgery was performed for lumbar vertebral column instability secondary to fractures (28 cases), spondylolisthesis (29), tumors (four), vertebral osteomyelitis (two), or postoperative causes (41). Pseudoarthrodesis due to failure of a prior fusion was present in 37 cases. The 55 men and 49 women (mean age 47 years, range 18 to 87 years) all presented with severe back pain. Signs or symptoms of neural compression were noted in 96 patients. Surgery consisted of neural decompression, internal fixation, and autogenous iliac bone grafting. Spondylolistheses were fused in situ, without reduction; otherwise, major spinal deformities were corrected. A total of 516 pedicle screws were placed. The mean extent of fusion was 2.7 motion segments (range one to six motion segments). A 96% fusion rate was obtained with a mean follow-up period of 20 months. There were no operative deaths. Major complications included one spinal epidural hematoma, three isolated nerve root deficits (two transient, one permanent), and three wound infections (two deep, one superficial). Instrument failure eventually developed in 18 patients; nine were asymptomatic with a solid fusion and did not require further treatment and the other nine were symptomatic or had a pseudoarthrosis and required operative revision. Pedicle screw-rod fixation offers biomechanical advantages compared to other forms of internal fixation for the lumbar spine. It enables short-segment fixation with preservation of lumbar lordosis and adjacent normal motion segments. This technique provides a highly successful method to obtain arthrodesis, even with prior pseudoarthrosis.


Syrinx shunt to posterior fossa cisterns (syringocisternostomy) for bypassing obstructions of upper cervical theca.

Syrinx shunts to the spinal subarachnoid space are likely to fail if the cerebrospinal fluid pathways rostral to the syrinx are blocked. To bypass obstructions at or below the level of the foramen magnum, a technique was developed for shunting the syrinx to the posterior fossa cisterns, termed "syringocisternostomy." Syrinxes were shunted to the cisterna magna in two patients with spinal arachnoiditis and to the cerebellopontine angle cistern in four patients with Chiari I malformations. There was symptomatic improvement and collapse of the syrinx in each case, with no complications or recurrences over a follow-up interval of 14 to 27 months (average 20.3 months). The surgical technique and results of treatment are described.


Shunt implantation: reducing the incidence of shunt infection.

Shunt infection remains the foremost problem of shunt implantation after mechanical malfunctions. Diversionary cerebrospinal fluid shunt implantation has a high complication rate, with 5% to 15% of such shunts becoming infected. Of these infections, 70% are diagnosed within 1 month after surgery and more than 90% within 6 months. Shunt infection in the vast majority of cases is therefore a complication of shunt surgery. The authors review their experience with shunt implantation during two time periods. From January, 1978, to December, 1982, 302 children with hydrocephalus underwent 606 operations. Among these children, 47 (15.56%) developed a proven shunt infection, with an incidence of infection per procedure of 7.75%. As a result of this study, a new protocol for shunt procedures involving modifications in the immediate pre-, intra-, and postoperative management of children undergoing shunt implantation was initiated. With this new protocol, 600 children underwent a total of 1197 procedures between January, 1983, and December, 1990. The incidence of shunt infection decreased dramatically, with two infections (0.33%) in 600 patients and a per-procedure rate of 0.17%. The overall annual risk of a shunt infection in the pediatric neurosurgical unit is currently 1.04%.


Outcome following hindbrain decompression of symptomatic Chiari malformations in children previously treated with myelomeningocele closure and shunts.

Between 1975 and 1989, 25 children treated with myelomeningocele closure and shunting for hydrocephalus at the Children's Hospital of Pittsburgh developed progressive lower brain-stem dysfunction from their Chiari malformation. Retrospective univariate and multivariate analyses of these cases were undertaken to assess the relationship between preoperative clinical factors and postoperative outcome. Since earlier reports have suggested that neonates with symptomatic Chiari malformations show a less favorable response than older children to craniocervical decompression, particular attention was directed at examining the effect of age on preoperative symptoms and postoperative outcome. Patients were subdivided by age into two groups, namely: 13 patients who became symptomatic before 2 months of age (neonatal group) and 12 older infants and children who developed initial symptoms between 6 months and 10 years of age. Once symptoms developed, patients in both groups deteriorated progressively until brain-stem decompression was performed. The mode of presentation and the rate and extent of neurological deterioration differed substantially in the two groups. Whereas the neonates typically showed rapid neurological deterioration and often manifested profound brain-stem dysfunction within a period of several days, the older patients experienced a more insidious symptom progression and rarely demonstrated the severe degree of impairment seen in the neonates. All patients underwent suboccipital craniectomy, cervical laminectomy, and dural decompression. A shunt from the fourth ventricle and/or syrinx to the subarachnoid space was placed in those with significant syringomyelia. Following surgery, 17 patients had complete or nearly complete resolution of all signs of brain-stem compression, three had mild to moderate residual deficits, and five showed no improvement. Outcome correlated closely with the preoperative neurological status. In particular, the presence of bilateral vocal cord paralysis was associated with a poor response to surgery (p < 0.001 on both univariate and multivariate analyses). Of the six patients (all neonates) who progressed to complete bilateral vocal cord paralysis before surgery, only one improved. In contrast, all patients with less profound but nonetheless severe deficits recovered function postoperatively. Although the neonates as a group had a poorer outcome than did the older patients (p = 0.02 on univariate analysis), this in large part reflected their more severe preoperative impairments; neonates who still had some preservation of vocal cord function before surgery subsequently did as well as the older patients. Accordingly, age did not prove to be an independent prognostic factor on multivariate analysis. Taken together, these results indicate that, in most patients with symptomatic Chiari II malformations (including neonates), neurological deficits are potentially reversible if hindbrain decompression is performed expeditiously.


Cerebral hemicorticectomy for epilepsy.

Hemicorticectomy resulted in total or near-total control of seizures in 10 of 11 children with chronic epilepsy. During a median follow-up period of 5.5 years, there have been no deaths or delayed complications. The surgical outcome after hemicorticectomy compares favorably with that of more extensive surgical procedures, yet is associated with significantly less risk. The technique for hemicorticectomy is described and illustrated.


Surgical management of symptomatic pineal cysts.

The authors present a series of six patients with large symptomatic benign pineal cysts and review the 27 patients previously reported in the literature. Patients with symptomatic pineal cysts most often present with one of three syndromes: 1) paroxysmal headache with gaze paresis; 2) chronic headache, gaze paresis, papilledema, and hydrocephalus; or 3) pineal apoplexy with acute hydrocephalus. Surgical intervention with radical cyst removal is the treatment of choice for all symptomatic pineal cysts. Complete cyst removal is desirable; however, radical subtotal resection is appropriate if the cyst cannot be easily separated from the quadrigeminal plate. Ventricular shunting should be reserved for patients with persistent hydrocephalus after cyst resection.


Extracranial complications of severe head injury.

In order to define the role of intracranial and extracranial complications in determining outcome from severe head injury, 734 patients from the Traumatic Coma Data Bank were analyzed. Nine classes of intracranial and 13 classes of extracranial complications occurring within the first 14 days after admission were analyzed, while controlling for age, admission Glasgow Coma Scale motor score, early hypoxia or hypotension, and severe extracranial trauma. Outcome for survivors was based on the last recorded Glasgow Outcome Scale score, obtained a median of 521 days after injury. Intracranial complications did not significantly alter outcome for the study group. Of the extracranial complications, pulmonary, cardiovascular, coagulation, and electrolyte disorders occurred most frequently at 2 to 4 days. Infections developed later, peaking at 5 to 11 days. Gastrointestinal, renal, and hepatic complications followed no specific time course. Electrolyte abnormalities were the most frequent occurrence (59% of patients) but did not alter outcome. Pulmonary infections (41%), shock (29%, systemic blood pressure < or = 90 mm Hg for 30 minutes or more), coagulopathy (19%), and septicemia (10%) were significant independent predictors of an unfavorable outcome. Backward-elimination, stepwise logistic regression modeling indicated that the estimated reduction of unfavorable outcome was 2.9% for the elimination of pneumonia, 3.1% for coagulation disturbances, 1.5% for septicemia, and 9.3% for shock. These data suggest that extracranial complications are highly influential in determining the outcome from severe head injury and that significant improvements in outcome in a sizeable proportion of patients could be accomplished by improving the ability to prevent or reverse pneumonia, hypotension, coagulopathy, and sepsis.


Unruptured aneurysms and postoperative volume expansion.

After a ruptured aneurysm has been clipped in patients with multiple aneurysms, the question often arises whether to use volume expansion and/or hypertensive treatment to prevent delayed cerebral ischemia (vasospasm). There is understandable concern regarding the possible rupture of unprotected aneurysms under additional hemodynamic stress. In a series of 199 patients with aneurysmal subarachnoid hemorrhage who underwent early surgery, 31 were left with one or more unprotected aneurysms postoperatively. All patients were treated with prophylactic volume expansion based on a previously reported protocol. Mean central venous pressure during treatment was 10.3 cm H2O and mean arterial blood pressure 141/76 mm Hg; volume expansion was continued for 7 to 10 days. Eight patients developed symptoms of delayed cerebral ischemia and required additional volume expansion and induced hypertension. After institution of hypertension, four of these patients experienced a reversal of their symptoms, while four others developed cerebral infarcts. One patient died from massive cerebral infarction following vasospasm refractory to all measures. No patient suffered rupture of an unprotected aneurysm during hypervolemic treatment. It is concluded that the benefit of prophylactic hypervolemic hypertension in postoperative aneurysm patients warrants its use even in patients with unprotected aneurysms.


Effects of intermittent reperfusion during temporal focal ischemia.

There is controversy regarding the role of intermittent reperfusion employed as a cerebroprotective measure when temporary arterial occlusion is necessary during repair of difficult aneurysms. The intraluminal suture middle cerebral artery (MCA) occlusion technique was used in 23 Wistar rats under barbiturate anesthesia to induce 60, 90, or 120 minutes of uninterrupted MCA occlusion. The total infarcted areas obtained were compared to those occurring in 27 animals subjected to identical cumulative ischemic periods but with 5 minutes of reperfusion after every 10-minute ischemic period. The mean total infarcted areas in the groups with 60-minute (1.8 +/- 0.89 sq mm), 90-minute (1.08 +/- 1.02 sq mm), and 120-minute (8.72 +/- 5.89 sq mm) intermittent reperfusion were significantly smaller than those occurring in the 60-minute (12.02 +/- 3.10 sq mm), 90-minute (11.54 +/- 2.68 sq mm), or 120-minute (30.43 +/- 6.51 sq mm) control groups, respectively (p < 0.05). Furthermore, there was no difference in the occurrence of blood-brain barrier breakdown, intraparenchymal hemorrhage, hemispheric edema, or seizures between control and intermittent reperfusion groups. The results support the hypothesis that intermittent reperfusion is beneficial if vessel occlusion is required during aneurysm repair.


Regional metabolism in experimental brain tumors in cats: relationship with acid/base, water, and electrolyte homeostasis.

Experimental brain tumors were produced in cats by xenotransplantation of the rat glioma clone F98 into the white matter of the left hemisphere. One to 4 weeks after implantation, local adenosine triphosphate (ATP), glucose, lactate, and tissue pH were measured via imaging techniques in cryostat sections passing through the center of the tumor and correlated with changes in water and electrolyte content. The tumors exhibited a heterogeneous metabolic pattern, with a tendency for ATP to decrease and lactate to increase during tumor development. Tissue pH was above 7.5 in tumors with high ATP content but it sharply declined at low ATP levels. In peritumoral edema, ATP also decreased and lactate increased but, in contrast to tumor tissue, pH became more alkaline. Metabolic changes were associated with edema formation, as evidenced by the rise in water and sodium content. There was a distinct difference between tumor tissue and peritumoral edema: in tumor tissue, pH declined with increasing water content, whereas in peritumoral edema it increased. These observations are interpreted as follows: 1) in tumor tissue, "lactacidosis" and ATP depletion are attributed to disturbances in blood flow, resulting in metabolic failure and the intracellular "cytotoxic" accumulation of water; 2) in peritumoral edema, "lactalkalosis" is the result of an efflux of (alkaline) lactate salts from the tumor into the expanded extracellular compartment, and the decrease in ATP is the volumetric effect of extracellular "vasogenic" edema fluid and not the result of cellular energy failure. These findings are of importance for the interpretation of volume-selective magnetic resonance spectroscopy and may contribute to the establishment of spectroscopic criteria for the evaluation of therapeutical interventions.


Variability of the territories of the major cerebral arteries.

Recent morphological and functional studies on the circle of Willis suggest that the areas of supply of the six major cerebral arteries show a considerable variation in distribution, in contrast to the relatively consistent pattern generally accepted; therefore, the cortical and intracerebral distribution of the territories of these arteries was investigated in 25 unfixed human brains obtained at routine autopsy. The six major cerebral arteries were simultaneously injected under the same pressure with different-colored Araldite F mixtures under standardized conditions to obtain the most realistic territorial distribution. The cortical boundaries were examined and recorded in relation to the cerebral gyri and sulci, and the territories of the anterior, middle, and posterior cerebral arteries were analyzed and compared. The intracerebral distribution of these territories was investigated after the injected brains were cut in parallel slices. The variability of the territories of these arteries was much larger than generally described in the literature. Twenty-six variations in the territory of the anterior cerebral artery, 17 variations in the area of the middle cerebral artery, and 22 variations in the area of the posterior cerebral artery were found in the cortex of 50 hemispheres. Intracerebrally, the anterior, middle, and posterior cerebral arteries contributed in varying degrees to the blood supply of the lobar white matter, the internal capsule, the caudate nucleus, and the lentiform nucleus. The large variation in the area in which the cortical and intracerebral boundaries between these territories was located was demonstrated by illustrating the minimum and maximum extent of each. The results are compared with prior findings, and their implications for both experimental model studies and clinical practice are discussed.


Angioplasty for basilar artery atherosclerosis. Case report.

A case is presented of severe atherosclerosis of the basilar artery, successfully treated with percutaneous transluminal balloon angioplasty. Crescendo daily transient ischemic attacks consisted of alternating hemiplegia and were refractory to medical management, including anticoagulation therapy. The clinical course, endovascular treatment, and results are described. Prior published experiences with this condition are reviewed.


Acute cauda equina syndrome from a ruptured aneurysm in the sacral canal. Case report.

The case is presented of a young woman with acute cauda equina syndrome from a ruptured aneurysm in the sacral canal. The lesion was associated with pathological enlargement of the lateral sacral arteries bilaterally, which presumably occurred to provide cross-pelvic collateral flow in response to the diversion of the right internal iliac artery for renal transplantation. The patient presented with signs and symptoms of spontaneous spinal epidural hemorrhage. The radiographic features of this lesion are described. In addition to angiography and partial embolization of the vascular supply, contrast-enhanced high-resolution computerized tomography was essential in the diagnosis and treatment of this unique aneurysm.


Bilateral morning glory syndrome associated with sphenoid encephalocele. Case report.

Morning glory syndrome is a congenital anomaly of the optic disc in which the disc is enlarged and excavated, with white glial tissue in the center. A case is presented of morning glory syndrome associated with sphenoid encephalocele, median cleft lip, and agenesis of the corpus callosum. A 22-day-old boy was referred to the Wakayama Medical College Hospital for management of dyspnea due to a soft-tissue mass in the oral cavity. Magnetic resonance imaging revealed a mass extending through a bone defect in the sphenoid region and into the oral cavity. Surgical repair was attempted through a bifrontal craniotomy. A bone defect was identified in the sphenoid plate, through which the arachnoid membrane was connected to the oral cavity. Both optic nerves were elongated and adhered to the encephalocele. The wall of the meningocele was compressed digitally through the oral cavity and sutured to the dura mater of the bone defect. The operative findings suggest that a basal encephalocele protruding from a bone defect in the sphenoid plate may disturb the normal development of the optic nerve.


Transaqueductal migration of a neurocysticercus cyst. Case report.

The clearly documented transaqueductal migration of a solitary intraventricular neurocysticercus cyst is described. The cyst was fortuitously demonstrated on magnetic resonance imaging during migration through the aqueduct. The radiological appearance and clinical significance of this condition are discussed.


A two-step supraorbital approach to lesions of the orbital apex. Technical note.

A two-step supraorbital approach to lesions of the orbital apex is described. This technique is easy and allows a satisfactory exposure of the region. In addition, the reconstruction resulting from the procedure is anatomically perfect. The authors report the operative results obtained in 20 patients and compare this two-step supraorbital procedure with similar surgical techniques described previously.


Development of neurosurgery at the University of Michigan.

The University of Michigan Medical School was founded in 1847, 30 years after the university itself. The first hospital in Ann Arbor was a 20-bed unit converted from a private house, that admitted only charity patients. The second University Hospital was built in 1925. The Section of Neurosurgery was founded by Dr. Max Peet, who was followed by Drs. Kahn and Schneider as section heads.


The death of Henry II of France.

On June 30, 1559, King Henry II of France (1519-1559), against the advice of his court ministers, participated in a fateful joust. The wooden lance of his younger opponent pierced the King's headgear, shattered into fragments, and penetrated his right orbit and temple. The King survived for 11 days following the mortal wound and was treated by two of the most distinguished physicians of the Renaissance: Ambroise Paré (1510-1590), the master surgeon, and Andreas Vesalius (1514-1564), the great anatomist. The unfortunate event, the nature of the injury, and the medical consultation between these eminent physicians should all be of interest to neurosurgeons. The historical consequences of this event are briefly reviewed.


Dual-isotope brain SPECT imaging with technetium-99m and iodine-123: clinical validation using xenon-133 SPECT.

Our phantom studies indicate that the energy resolution (9.7% FWHM) of a new three-headed single-photon tomograph (PRISM-3000) separates the distribution of 99mTc from 123I for 10% asymmetric or 15% or 10% centered 99mTc windows when combined with a 10% asymmetric 123I window. This technique is now applied to the simultaneous measurement of resting rCBF and changes induced by vasodilation (1 g acetazolamide) in 10 subjects with cerebrovascular disease. Resting and vasodilated 133Xe SPECT images were obtained first. Within 48 hr, 99mTc HMPAO was given at rest, acetazolamide injected, and after 20 min either [123I] IMP or [123I] HIPDM was administered. Subjects were scanned for 99mTc and 123I simultaneously using 10% asymmetric windows. Regression analyses demonstrated a linear relationship between 133Xe SPECT and dual-isotope SPECT measurements of lesion-to-cerebellum ratios in baseline (r = 0.92), vasodilated (r = 0.86) and rest-minus-vasodilated data (r = 0.85). Technetium-99m and 123I images obtained through dual-isotope imaging are by definition in perfect anatomic registration.


The role of sestamibi scintigraphy in the radioisotopic assessment of myocardial viability.

The relationship between sestamibi uptake as a marker of myocardial viability and postrevascularization function recovery is still to be defined. We studied 14 patients (13 males, 1 female, mean age 55 +/- 7 yr, range 35 to 64 yr) with sestamibi scintigraphy, quantitative coronary angiography and two-dimensional echocardiography. Sestamibi uptake was quantified from planar images and expressed as percent of maximal activity in each projection using a 13-segment model. All defects were subgrouped on the basis of the severity of reduction in sestamibi uptake; the limit of viability was set at 2.5 s.d. below the normal uptake (55%). Echocardiography was analyzed using a score index ranging from 1 (normokinesis) to 4 (dyskinesis) and a corresponding regional model. Before revascularization, 42 segments were grouped as normal (coronary stenosis < 50% and normal function, Group 1); of the remaining 140 segments related to > 50% coronary stenosis, 67 had normal wall motion (Group 2) and 73 showed regional dyssynergies (Group 3). Sestamibi percent activity was high in Group 1 and significantly reduced in both Group 2 and 3 segments. Pre- and postrevascularization echocardiography was compared in all patients. Sestamibi sensitivity and specificity in the detection of postrevascularization recovery of function was 83% and 71%, respectively; positive predictive accuracy was 79%. The presence of a severe defect identified most of those segments with wall motion abnormalities that did not recover following coronary revascularization; however, sestamibi overestimated rest perfusion defects in 25% of territories supplied by stenotic coronary arteries that had normal wall motion at rest. Sestamibi appears to be primarily a perfusion agent that can provide limited information regarding viability.


PET-fluorodeoxyglucose of cranial and spinal neuromas.

Five patients with eighth nerve, one with ninth nerve and one with cervical neuromas were studied with PET and [18F] fluorodeoxyglucose (FDG). Four of the patients had had surgery prior to the PET study, and six patients had subsequent surgery. All tumors were well-visualized on the PET images. Only one patient with bilateral acoustic neuroma exhibited tumor recurrence or growth after the PET study; these two lesions showed the highest FDG uptakes in the PET studies (tumor-to-cerebellum ratio of 0.93-0.98). All other tumors were relatively hypometabolic (tumor-cerebellum ratios of 0.43-0.65) and showed no tumor growth or recurrence during follow-up periods ranging from 5 to 8 yr. These results suggest that PET-FDG may be of value in the evaluation of cranial and spinal schwannomas.


Can dynamic krypton-81m imaging separate regional ventilation and volume?

This study explores the assumption that 81mKr static images represent regional ventilation. Dynamic acquisition of 81mKr ventilation images permits creation of time-activity curves and the possible separation of the confounding influences of ventilation and volume. By using a two-compartment gas mixing lung phantom, the results demonstrate that both total and tidal 81mKr are closely related to regional ventilation. In 61 children and 15 adult volunteers, there was good agreement between fractional ventilation assessed by total and tidal 81mKr. The dynamic steady-state ventilation image can be analyzed to separate tidally exchanged and resident 81mKr. This may allow regional ventilation to be distinguished from regional volume.


Brain SPECT in neonates following extracorporeal membrane oxygenation: evaluation of technique and preliminary results.

Extracorporeal membrane oxygenation (ECMO) is a life-saving procedure in neonates with refractory respiratory failure that has been used at our institution since 1985. In an attempt to study its clinical value, regional cerebral blood flow (rCBF) alterations were measured using SPECT and 99mTc-HMPAO in 13 newborns following ECMO. Eight infants were studied after ECMO with reanastomosis of the right common carotid artery (RCCA), two with the permanent ligation of the RCCA, and three after veno-venous ECMO. Brain SPECT was technically satisfactory in all newborns using a triple-head SPECT system. Altered rCBF was found in 7 of 13 infants. In five newborns, there was a decrease in rCBF within the ipsilateral hemisphere, and in one infant, contralateral hemisphere was involved. In one infant, there was bilateral hemispheric involvement. The infant underwent cardiopulmonary resuscitation prior to ECMO and exhibited clinical features of hypoxicischemic encephalopathy at the time of SPECT. Only 2 of 13 newborns demonstrated morphologic changes on neuroimaging modalities such as cranial ultrasonography, computed tomography and magnetic resonance imaging. Our study demonstrates that: (1) functional brain imaging is feasible in neonates after ECMO; (2) SPECT has potential for demonstrating rCBF deficits not detectable by neuroanatomic imaging modalities; and (3) SPECT has potential clinical value in long-term follow-up of neurodevelopmental outcome after ECMO.


Human pharmacokinetics and radiopharmacological studies of the myocardial perfusion agent: technetium (2-carbomethoxy-2-isocyano-propane)6+.

The myocardial perfusion agent technetium (2-carbomethoxy-2-isocyano-propane)6+ (99mTc-CPI) is unique from other cationic technetium isonitrile complexes in that it exhibits moderate washout from the heart and rapid hepatobiliary clearance in animal models and human volunteers. Dynamic imaging and HPLC analysis were performed in humans and guinea pigs to outline the pharmacological basis of its pharmacokinetics. Enzymatic hydrolysis of the terminal ester groups in blood was found to occur at a moderate rate producing new species that have been shown not to accumulate in heart tissue. However, after extraction by the heart, liver or kidneys, the 99mTc-CPI complex undergoes metabolism at a much slower rate than observed in the blood. Differences in hydrolysis rate and products obtained indicate separate mechanisms of hydrolysis occurring in blood and other organs. It is proposed that the heart washout occurring after hydrolysis produces a neutral compound which is no longer retained by the negative cytosolic and mitochondrial membrane potentials in myocardial tissue.


Specific and nonspecific immunoassays to detect HAMA after administration of indium-111-labeled OV-TL 3 F(ab')2 monoclonal antibody to patients with ovarian cancer.

The development of human anti-mouse antibodies (HAMA) may cause problems in radioimmunotargeting studies, but may also improve survival of patients. To identify the presence of HAMA in blood samples from patients intravenously injected with 1 mg of 111In-labeled OV-TL3-F(ab')2, we developed three specific OV-TL 3-based HAMA assays and tested these along with two commercially available nonspecific HAMA assays (Sorin and Immunomedics). The specific assays were positive for HAMA with 10 postinjection serum samples from 7 patients. Eight of the 10 samples were also HAMA positive with one or both nonspecific HAMA assays. Conflicting results were observed with half the number of samples. The two nonspecific assays also reacted positively with another 11 serum samples from 5 patients including their preinjection samples. Despite some contradictory results, the nonspecific HAMA assays identify both pre-existent and Mab-induced HAMA, whereas the specific OV-TL3-based HAMA assays identify specific immune-responses occurring after the OV-TL 3 injection.


Dynamic SPECT imaging of dopamine D2 receptors in human subjects with iodine-123-IBZM.

We studied the uptake, distribution, metabolism and washout of the dopamine D2 receptor ligand [123I]IBZM in healthy subjects (n = 12) with dynamic brain SPECT. The highest radioactivity level was detected in the striatum. Operationally-defined striatal "specific" uptake peaked at 69 min postinjection of radioligand and showed a gradual decline of 15% per hour thereafter. "Specific" uptake at maximal counts represented 53% of the total striatal radioactivity. Two subjects received haloperidol (20 micrograms/kg i.v.) 80 min postinjection of radioligand. Haloperidol caused a 2.6-fold increase in the rate of washout of specific striatal activity in comparison to that in the 10 control subjects and was consistent with drug-induced displacement of radioligand from the dopamine D2 receptor. Two classes of metabolites were detected in plasma and urine: a polar fraction, not extracted by ethyl acetate, and a nonpolar, extractable fraction consisting of parent compound and two compounds having shorter retention times on reversed-phase HPLC. Greater than half the plasma parent was metabolized within 10-15 min after administration. The volume of distribution, estimated from the peak arterial plasma concentration at 50-75 sec, was 7.7-10.2 l; the free (nonprotein bound) fraction of [123I]IBZM after in vitro incubation with blood or plasma was 4.4% +/- 0.4%. These results suggest that [123I]IBZM exhibits uptake in brain regions with high D2 receptor density and shows a relatively stable washout during which drugs affecting dopaminergic transmission may be administered.


Intratumoral distribution of fluorine-18-fluorodeoxyglucose in vivo: high accumulation in macrophages and granulation tissues studied by microautoradiography.

While 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) is a useful tumor imaging agent, its intratumoral distribution has not been described well at the cellular level. In order to demonstrate cellular localization of [18F]FDG and 2-deoxy-D-[3H]glucose (3H-DG) uptake by the tumor in vivo, C3H/He mice transplanted subcutaneously with FM3A tumors were studied 1 hr after intravenous injection of [18F]FDG or 3H-DG using micro- and macro-autoradiography. Fluorine-18-FDG and 3H-DG showed the same distribution pattern in the tumor with both autoradiographic methods. The newly formed granulation tissue around the tumor and macrophages, which were massively infiltrating the marginal areas surrounding necrotic area of the tumor showed a higher uptake of [18F]FDG than the viable tumor cells. A maximum of 29% of the glucose utilization was derived from nontumor tissue in this tumor. The comparison of double-tracer autoradiographic distribution patterns of [18F]FDG and [6-3H]-thymidine showed the differences and the similarities between glucose utilization and the DNA synthesis. Whole proliferating tissue metabolizes [18F] FDG but not vice versa. High accumulation of [18F]FDG in the tumor is believed to represent high metabolic activity of the viable tumor cells. Our results showed that one should consider not only the tumor cells proper but also the non-neoplastic cellular elements, which appear in association with growth or necrosis of the tumor cells, for precise analysis of [18F]FDG uptake in tumor-bearing subjects, especially after anti-neoplastic treatment.


Metabolic design of combination therapy: use of enhanced fluorodeoxyglucose uptake caused by chemotherapy.

In order to quantify effects of an experimental chemotherapy, MCF7 cells were studied with 14C-fluorodeoxyglucose (FDG) and high-performance liquid chromatography (HPLC). Uptake measurements were performed 1 and 4 hr after the end of a therapy with hexadecylphosphocholine (HPC). A dose- and time-dependent increase of the FDG uptake after therapy was observed, with a maximum at 1 hr after therapy. These data were used to develop a new metabolic design of combination treatment. Several time-dose combinations of HPC and deoxyglucose (DOG) were analyzed for their effects on growth inhibition. The combinations using DOG in the period of pronounced enhancement of FDG uptake (1 hr after HPC treatment) were found to be the most effective with an improvement of up to 520% in growth inhibition. This metabolic design of combination treatment may also be applied in vivo, and PET can be used to optimize the time and dose schedule of the modified treatment protocol.


Comparison of technetium-99m-glucarate and thallium-201 for the identification of acute myocardial infarction in rats.

The scintigraphic identification of acute severe ischemic myocardial injury requires a marker that localizes rapidly and specifically in zones of damaged myocardium. Technetium-99m-glucarate, a six-carbon dicarboxylic acid, which behaves in vivo somewhat like fructose, was recently described as a marker of severe acute ischemic injury with necrosis. This study was performed to determine the interval between the onset of myocardial ischemia and initial uptake and the duration of a positive scan in experimental animals. Serial injections and images were recorded over 10 days following ligation of the left anterior descending coronary artery of the rat. The distribution of 99mTc-glucarate was compared to that of regional myocardial perfusion monitored with 201TI. The findings on radionuclide imaging were compared to histologic changes in the myocardium. Sequential pinhole images of both radionuclides were collected at 3 hr, 24 hr, 72 hr and 7-10 days following ligation. Ten rats had normal 201TI distributions, no uptake of glucarate and no evidence of infarction by TTC staining at autopsy. Twenty-one rats had either 201TI lesions or evidence of infarction at autopsy. In 17 of these rats, significant acute 99mTc-glucarate uptake was noted, decreasing at 24 hr, and was not seen at 72 hr or 7-10 days. The extent of perfusion abnormality was greatest at 3 hr in most animals; the lesion decreased in four (33%), increased in one (8%) and remained stable in the remainder. These data suggest that 99mTc-glucarate may be a useful marker of acute myocardial injury.


Imaging of cardiac transplantation rejection in primates using two new antimyosin agents.

Indium-111-labeled monoclonal antimyosin Fab has been used to image myocardial infarction, myocarditis and cardiac transplant rejection with localization in myocytes that have suffered irreversible loss of cell membrane integrity. Technical factors potentially limiting clinical usefulness of 111In antimyosin include dosimetry (72 hr half-life of 111In), slow blood clearance of antibody proteins delaying optimal imaging to 24 to 48 hr postinjection and nontarget organ uptake. Therefore, two new antimyosin imaging agents experimentally shown to potentially improve dosimetry, shorten time from injection to imaging or decrease nonspecific cell binding were evaluated in a primate cardiac transplant model. The two agents evaluated were polylysine 111In-antimyosin (0.023 mg Fab modified with a 3.3 kd polymer of polylysine and labeled with 111In) and 99mTc-antimyosin (0.5 mg Fab' antimyosin labeled using the RP-1 ligand technique). A total of eight baboons were studied: three with heterotopic (cervical) xenographs, three with orthotopic allographs and two control animals. Each animal was injected first with 12-23 mCi of 99mTc-RP-1 antimyosin and 5-16 hr after completion of imaging, was injected with 0.72-1.88 mCi of 111In-polylysine antimyosin (PIs) and reimaged 12-48 hr later. The imaging results were compared to the histology of the animals. Biexponential curves were fit to the blood sample data and rate constants were determined and expressed as T1/2 values. There were no significant differences between the two agents in either the early fast components or the late slow components. On planar imaging, there was blood-pool activity at 10-12 hr postinjection of both agents, but by 16-24 hr postinjection, blood pool was negligible on the 111In-PIs scans. Both agents were concentrated in the rejected cardiac tissue. The slow blood-pool clearance combined with the 6 hr half-life of 99mTc-RP-1 AMA make this agent less promising for detection of diffuse myocardial uptake than 111In Fab modified with polylysine.


Experimental and clinical analysis of the characteristics of a chimeric monoclonal antibody, MOv18, reactive with an ovarian cancer-associated antigen.

Monoclonal antibody (Mab) MOv18 preferentially reacts with gynecological carcinomas. We have analyzed the characteristics of murine MOv18 (m-MOv18) and chimeric MOv18 (c-MOv18). We found no differences in affinity and binding to IGROV1 cells between c-MOv18 as IgG and F(ab')2 fragments and m-MOv18. In nude mice bearing IGROV1 xenografts, maximum tumor uptake 6-15 hr after i.v. injection of radiolabeled m-MOv18 IgG, c-MOv18 IgG, c-MOv18 F(ab')2 and a control IgG, 2C7, was 10%, 11%, 3% and 4.5% of the injected dose/g (%ID/g), respectively. M- and c-MOv18 IgG retained this level for several days, while c-MOv18 F(ab')2 and 2C7 cleared rapidly from the tumor. Uptake in normal tissues was low, with the exception of high uptake in kidneys for c-MOv18 F(ab')2. Tumor/blood ratios for c-MOv18 F(ab')2 were sixfold higher than for IgG. Radiation absorbed doses to tumor tissue delivered by 10 microCi iodinated m-MOv18 IgG, c-MOv18 IgG and c-MOv18 F(ab')2 were 39 cGy, 49 cGy and 5 cGy, respectively. A cocktail of 125I-c-MOv18 IgG and 131I-c-MOv18 F(ab')2 injected i.v. into an ovarian cancer patient, localized specifically in the tumor. Ovarian cancer tissue samples obtained 2 days postinjection showed a mean uptake of 1.2 x 10(-3) and 2.7 x 10(-3) %ID/g for c-MOv18 IgG and c-MOv18 F(ab')2, respectively. Results from these in vitro and in vivo experiments indicate that c-MOv18 has promise as a Mab for clinical use.


Pretargeted immunoscintigraphy: effect of hapten valency on murine tumor uptake.

A method of radioimmunoscintigraphy using bivalent "Janus" haptens with an apparent enhanced affinity ("avidity") for the antibody is described. Janus with 50 micrograms pretargeted Mab WC3A11 resulted in significantly higher murine tumor concentrations (approximately 7%/g) compared to monovalent haptens (approximately 1.4%/g, p < 0.001), and the same high tumor-to-background ratios (approximately 3/1). Janus was synthesized by coupling two molecules of BABE together with a 1,4 butanedithiol linker. Janus itself was rapidly excreted (T1/2b = 42 min) by the kidneys and did not concentrate in any other organs or tissues. Three-step pretargeted immunoscintigraphy (binder, chaser, tracer) with 111In- or 67Ga-Co(III) Janus produced excellent mouse tumor images in 3 hr with high tumor-to-background ratios. The use of short-lived tracers, such as 99mTc and 68Ga, with a T1/2p of hours to image antibodies that localize slowly over several days in vivo is accessible with this new technology.


Abnormal intracerebral thallium localization in a bacterial brain abscess.

A 56-yr-old man with a prior history of renal cell carcinoma had moderately intense abnormal localization of 201Tl-chloride in a solitary brain lesion which was discovered to be a bacterial abscess. The organisms isolated by culture included Actinomycosis odontolyticus, Peptostreptococcus and Hemophilus aphrophilus. Because of the clinical presentation, MRI characteristics and thallium scintigraphic findings, the lesion had been felt to represent either a primary or a metastatic neoplasm. This case illustrates the need for caution in the interpretation of thallium brain scintigram.


PET scanning of iodine-124-3F9 as an approach to tumor dosimetry during treatment planning for radioimmunotherapy in a child with neuroblastoma.

A patient with advanced neuroblastoma who had failed chemotherapy presented with a large abdominal mass and virtually total bone marrow replacement by tumor on repeated marrow biopsies. She was considered a candidate for a Phase I 131I-3F8 radioimmunotherapy trial, (MSKCC 89-141A). As a potential aid to treatment planning, a test dose of 124I-3F8 was injected and the patient was imaged over the 72 hr postinjection using two BGO based PET scanners of different designs. Time activity curves were obtained, and the cumulated activity concentration of radiolabeled 3F8 in tumor was determined. Based on MIRD, an estimated radiation absorbed dose for 131I-3F8 was 7.55 rad/mCi, in the most antibody avid lesions. Because of low uptake and unfavorable dosimetry in some bulky tumor sites, it was decided not to treat the patient with radiolabeled antibody. Positron emission tomography of 124I-labeled antibodies can be used to measure cumulated activity or residence time in tumor for more accurate estimates of radiation absorbed tumor dose from radioiodinated antibodies and can help guide management decisions in patients who are candidates for radioimmunotherapy.


Indium-111-leukocyte and gallium-67 imaging in acute sarcoidosis: report of two patients.

Two young women with acute sarcoidosis underwent (111)In-labeled autologous leukocyte imaging because of persistent fevers. Images of one of the women demonstrated faint thoracic lymph node uptake of labeled cells, but no discrete focus suggestive of infection was seen. Images of the second woman were normal. Gallium-67 imaging, performed 48 hr after the leukocyte studies, revealed multiple areas of abnormal radiotracer accumulation corresponding to regions of active sarcoid in both women. These cases suggest that leukocyte imaging is not useful for assessing the extent of disease in patients with sarcoidosis. This technique may be valuable, however, in excluding superimposed infection in these individuals.


An autonomously functioning thyroid carcinoma associated with euthyroid Graves' disease.

A 39-yr-old man with an autonomously functioning thyroid carcinoma is presented. Only 17 similar cases have been reported in the literature. The patient had unilateral Graves' ophthalmopathy. He was euthyroid as reflected by normal TSH concentration, whereas the results of a T3 suppression test established the presence of autonomous thyroid function. A thyroid scan with (123)I revealed a hot nodule corresponding to the location of a papillary carcinoma and remained substantially unchanged after T3 administration. The hyperfunction of the carcinoma itself was clearly confirmed by the intense concentration of (131)I within the tumor on microautoradiograms. While a hot nodule on radioiodine scan is unlikely to be malignant, the possibility of carcinoma should not be overlooked.


Dual-isotope brain SPECT imaging with technetium-99m and iodine-123: validation by phantom studies.

Phantom studies were employed to determine whether the enhanced energy resolution (9.7% FWHM) of a new high-resolution, three-headed single-photon emission computed tomograph might permit the simultaneous acquisition of 99mTc and (123)I. Various window widths (15% and 10%) and positions (centered and asymmetric to the photopeak) were used to examine cross-contamination between these two isotopes. Brain phantom experiments using a 15% centered 99mTc window in conjunction with a 10% asymmetric (123)I window (upper half of the (123)I photopeak) demonstrated that approximately 95% of observed counts were derived from the isotope of interest. Shifting the (123)I window from asymmetric to centered resulted in a significant increase in contamination of the (123)I window. Shifting the 99mTc window from centered to asymmetric did not significantly alter image quality for 99mTc. Separate experiments employing vials with varying isotope concentrations demonstrated that quantitative recovery from mixed 99mTc and (123)I sources was equivalent to that from matched single-isotope sources (r2 > or = to 0.90).


Prognostic value of captopril renal scintigraphy in renovascular hypertension.

This study evaluates the prognostic value of captopril renal scintigraphy in hypertensive patients undergoing renal artery revascularization. Preoperative studies of 51 patients were correlated with blood pressure results at 6- and 12-mo follow-up. Captopril-renal scintigraphy was carried out 1 hr after oral administration of 50 mg of captopril, using either 220 MBq of 99mTc-DTPA or 74 MBq of 99mTc-MAG3, followed by a baseline study in case of abnormal results. Evidence of amelioration or normalization in relation to captopril study was considered predictive of blood pressure control following treatment. Blood pressure response was favorable in 37 patients, but failed to show any improvement in 14. The scintigraphic test was positive in 33 patients (15 cured, 17 improved, 1 failed) and negative in 18 (3 cured, 2 improved, 13 failed). Sensitivity and specificity for renovascular hypertension was 86.5% and 93%, respectively. For blood pressure cure and improvement, the test had positive and negative predictive values of 97% and 72%, respectively. A positive preoperative captopril renal scintigraphic result is a strong predictor of hypertension curability by renal artery revascularization.


The "well tempered" diuretic renogram: a standard method to examine the asymptomatic neonate with hydronephrosis or hydroureteronephrosis. A report from combined meetings of The Society for Fetal Urology and members of The Pediatric Nuclear Medicine Council--The Society of Nuclear Medicine.

Perinatal hydronephrosis (HN) and hydroureteronephrosis (HUN) are recognized more frequently as the routine use of prenatal ultrasonography increases. The decision-making process for those instances of urinary tract dilatation that require surgical correction and those that do not is based in part on the findings of diuresis renography. The methodology for performing this test has differed among nuclear medicine practitioners and the surgical findings are occasionally discrepant from the diuretic renogram interpretation. Consequently, the Society of Fetal Urology (SFU) and the Pediatric Nuclear Medicine Council (PNMC) of the Society of Nuclear Medicine met to develop by consensus a more uniform methodology. A standard method has been agreed upon for the following facets of diuretic renography: patient preparation (hydration and bladder catheterization), diuresis renography technique (radiopharmaceutical used, patient position during examination, data acquisition parameters, diuretic pharmaceutical and dosage, time of injection and regions of interest to monitor diuretic effect), and data analysis (percent differential renal function, curve pattern analysis and methods of measuring diuretic response). Pooled diuresis renogram data are being collected for analysis for correlation with surgical results and clinical outcomes to determine the most appropriate information to be derived from the diuretic renogram in neonates with HN and HUN.


Diffuse abdominal uptake of technetium-99m-methylene diphosphonate in a patient on continuous ambulatory dialysis during bone scintigraphy.

Extra-skeletal uptake of bone seeking radiopharmaceuticals has been documented by scintigraphy. We present a case of diffuse uptake of 99mTc-methylene diphosphonate (MDP) in the abdomen of a patient while undergoing continuous ambulatory peritoneal dialysis (CAPD) who had no symptoms or findings referable to the abdomen. We hypothesized that the 99mTc-MDP crossed the peritoneal membrane across a concentration gradient. An in-vitro simulation confirms that 99mTc-MDP will cross a semi-permeable membrane. Diffuse uptake of 99mTc-MDP may be a normal variant in patients on CAPD who have no signs or symptoms of peritonitis.


Assertiveness training: does it make a difference?

The impact of assertiveness training on job-related functioning has not been evaluated. This study, conducted in a tertiary care psychiatric facility, assessed whether assertiveness training changed nurses' perceptions of assertiveness, attitudes toward power, functioning within the nursing team, and functioning within the multidisciplinary team. This article describes a four-part assertiveness training course that was found to significantly affect feelings of assertiveness.


Teaching the nurse to teach with health information videos.

Using health information videos is a common way to teach hospitalized patients. This article describes a study of medical and surgical patients in an acute care hospital. In Phase I, patients' frequency of Patient Health Information Television use and their knowledge of programs and scheduling were evaluated. Phase 2 identified patients' learning after viewing selected programs. In Phase I, frequency of use, peak viewer time, and viewer encouragement strategies were revealed. In Phase II, the efficacy of televised patient education was documented. Results indicate that nursing staff development educators should teach nurses how to work with this educational medium.


Feeling refreshed: helping RNs return to the work force.

In light of the nursing shortage, many hospitals are turning to refresher courses to meet staffing needs. To be successful, the course must be designed to meet the needs of both the participant and the hospital. Although the exact structure of the course will vary by institution, this article details steps taken at one hospital to help registered nurses return to nursing.


Opioid analgesics: nurses' knowledge of doses and psychological dependence.

Lack of education of health professionals, including nurses, is frequently cited as a major reason for undertreatment of pain. Very recent surveys have revealed an urgent need for basic and continuing nursing education to address this problem. For example, little time is spent on the topic of pain in many baccalaureate nursing programs, nursing textbooks lack correct information about opioid addiction, and most practicing nurses currently do not possess knowledge about opioid analgesics that would enable them to administer opioids effectively. The authors report on a survey of 1,781 practicing nurses' specific knowledge deficits regarding opioid analgesics and propose some solutions.


A new clinical educator role: bridging the education-practice gap.

A new clinical educator role implemented at Georgetown University Hospital is described in this article. Nurses in this role assume dual responsibilities for nursing staff development and clinical supervision of baccalaureate nursing students. These clinical educators have joint appointments in the Department of Nursing and the School of Nursing. This role helps to bridge the education-practice gap and encourages a more efficient use of nursing resources.


Innovative staff development approaches for NCLEX-RN success.

NCLEX-RN Licensure success is achievable when the institution provides administrative support, has a committed staff development department, and allocates necessary resources and support services. This program was designed and delivered in a cost-effective manner. The candidates attended the on-site review course and tutoring sessions before their assigned work time. The tutoring sessions offered by the staff development instructors were held during their regularly scheduled hours. The consultant's fee for the on-site review course was $200 per eligible candidate, for a total of $7,600. Specifically, employers and staff development departments must take a strong role not only in acclimating newly graduated and foreign-educated nurses to the professional environment, but also in helping to prepare them for the NCLEX-RN Licensure Examination. Thus, staff development educators can effectively ensure that their institutions will not lose valuable registered nurses.


A hierarchical approach to unit-based nursing orientation.

Using a hierarchical approach to orientation is a means to address the needs of both the orientee and the institution. The Hierarchical Orientation Model, described in this article, focuses on the development of skills in patient assessment and management and on organization sensitivity and integration. The model is based on adult learning principles that include building on previous knowledge and self-paced learning. Although developed for a tertiary pediatric hospital, the Hierarchical Orientation Model can be applied to other settings.


Helping new graduates succeed at the NCLEX-RN experience: evaluation of an anxiety-reducing workshop.

A descriptive, longitudinal study was conducted to determine the effectiveness of a 2-day workshop designed to reduce the anxiety levels of new graduates participating in the NCLEX-RN examination. A hospital nurse administrator, in collaboration with nurse educators, provided a multimodal in-service program. "Test wiseness," or test-taking strategies, and exercises related to physical and emotional well-being, were included for three groups of new graduates. Using Zung's Self-rating Anxiety Scale to collect data, reduction in anxiety after the workshop and at the completion of the NCLEX-RN experience was identified. All participants in the program passed the NCLEX-RN examination.


Mouth-to-mask resuscitation in the hospital: perceived problems of staff and variations in technique.

Mouth-to-mask resuscitation is used by many hospitals to implement "Universal Infection Precautions" and is now mandatory for health care Basic Cardiac Life Support (BCLS) courses nationwide. In the past, mouth-to-mask resuscitation was not routinely performed in hospital settings, and was optional in health care BCLS courses. This study suggests needed changes in mouth-to-mask resuscitation training and use. These findings can be used by nurse educators who are frequently responsible for implementing and evaluating BCLS programs.


Effect of Orem's model on nurse attitudes and charting behavior.

This article describes a program evaluation that examines the effect of Orem's self-care nursing model on the attitudes of nurses and on charting behavior. Implementing Orem's model increased staff nurse satisfaction with nursing and enhanced nurses' perception of the value of patient teaching.


Planning a peer review program.

The purpose of this study was to provide a basis for the planning and subsequent implementation of a peer review program, concomitant to exploring the perceptions of registered nurses regarding initiating a peer review program in a small midwestern hospital. The study findings indicated that registered nurses liked the peer review process, perceived peer review as helping their professional growth, and indicated a strong desire for education and in-service. Based on the study results, planning and recommendations for further implementation are discussed.


Legal and ethical issues in HIV testing, Part 1.

HIV antibody testing presents multiple and complex legal and ethical issues. Nurse executives must be knowledgeable about these issues and their potential impact on administrative practice. In this two-part series, the author presents legal and ethical issues related to testing. Part 1 focuses on the AIDS epidemic, the ELISA test, informed consent, confidentiality, and mandatory vs. voluntary testing.


Characteristics of critical care nursing internship programs.

Development of programs to prepare new graduate nurses to work in critical care units has been a priority for nurse educators for many years. Despite the presence of many such internship programs, little data are available about the characteristics of such programs. Results of this study suggest that the development of internship programs designed to prepare new graduate nurses in critical care nursing continues to be a priority. The standards used by these programs are individualized and are often reflective of the unique needs of the institution. Costs of these programs are quite high. Recommendations for future directions based upon the results of the study are offered.


Team building for the staff development department.

Development of effective teamwork is a deliberate process. The leader assumes a major role in this process. The payoff for team building begins with the increased professional growth of members that may ultimately result in improved overall organizational effectiveness. This article describes the major roles a leader plays in helping groups become teams.


Contract management. Filling the void created by CNE vacancies.

Contract management can provide interim chief nurse executives (CNEs) during the search process for a permanent executive. Experienced and effective, interim nursing executives can communicate to all audiences, prepare the organization for the next permanent nursing executive, and their presence avoids problems that arise during a long recruitment period. Typically, interim nursing executives find that working through contract management is a rewarding and challenging experience.


Developing home care standards you can count on ... and cost on!

Cost management is a six-step process that begins with identifying important activities of patient care, identifying desired outcomes of patient care, and the most predictable and efficient process to be used to ensure outcome accomplishment. The more caregivers and managers understand the cost-benefit connection between patient care and resource costs, the easier it will be for them to manage (rather than be a victim of) quality, productivity, and profitability.


Designing roles for assistive personnel in a rural hospital.

The role development of assistive personnel has become more important in rural hospitals because of the limited professional nursing supply. St. Mary's Hospital has fostered interdepartmental collaboration to reallocate duties to personnel who are best qualified to perform them. The dyad model, uniquely tailored to this hospital's needs, has resulted in the more efficient and effective use of personnel.


Teleconferencing. Home health administrators and educators enhance graduate education.

In light of the current condition of university budgets, enhancing graduate education can be a challenge for nurse educators. One effective and inexpensive strategy is teleconferencing. This strategy allows graduate students to network with nurse leaders nationwide without the expense of travel. Teleconferencing could also be adapted in other areas to bring service and educational professionals together.


Operating room productivity. An evaluation format.

Operating room (OR) directors are frequently faced with the challenge of explaining or justifying OR productivity and the OR staffing budget. This justification may occur annually in conjunction with their budget submission or when consultants are employed to evaluate and improve OR productivity. Whatever the circumstance, a simple step-by-step format that helps physicians and administrators understand the impact of productivity on the nursing budget can be most useful. The authors present a format that was successfully used at a Boston teaching hospital.


A strategy for growth in home care. The clinical nurse specialist.

One of the most challenging problems that faces today's home healthcare providers is how to deliver quality care within the constraints imposed by changing population, limited resources, and regulations. This problem is particularly apparent to those who provide rural healthcare. Use of the clinical nurse specialist can promote quality care while facilitating the development and expansion of home health services.


Nursing research in the VA system. A consortium approach.

Five Veterans' Administration Medical Centers formed a consortium to promote nursing research. Consortium arrangements focusing on research are reviewed based on the literature, the consortium's experience, and a survey of 171 VA facilities. Consortiums are suggested for multisite facilities, such as city, state, proprietary, and religious hospital systems, to increase the quality and quantity of nursing research where institutional mechanisms for overcoming the difficulties of meeting and sharing information are already in place.


Optimizing nursing information systems.

Financial, billing, and admission/discharge/transfer software applications have been available for years. Many administrators are purchasing systems to obtain automation to support nursing needs. However, administrators cannot rely on internal experience or software vendors to design their systems because not many have been operational long enough to have been sufficiently tested. In this article, the author provides a background of current functionality available, how clinical applications can interface for efficient documentation, and a strategy for developing the design of a new system.


The handwriting on the wall. Warning signs of impending job loss.

Can nurse executives read the handwriting on the wall when they or another nurse executive are facing a forced resignation or termination? What are the warning signs of an eroding job position, including the relationship between the chief nurse executive and the chief executive officer? How much time does a nurse executive typically have in the job once the warning signs begin to show? The authors discuss these questions and specific tactics and strategies suggested by warning signs.


A new look for quality in home care.

The management of quality is being transformed in healthcare. Continuous improvement is a cornerstone to this new look at quality. However, no continuous quality program will succeed without incorporating the values and wants of the consumer of care and the end point they want to reach. This article presents an overview of the values to consider and the way to define outcomes.


Community-hospital partnerships. The Quick Response Team.

The Quick Response Team project was an intervention designed and implemented by the Capital Regional District Care Program in partnership with the Greater Victoria Hospital Society. The aim was to address the health needs of frail elderly with multiple social, emotional, physical, and medical problems who were at risk for a custodial admission to acute care. The result was an innovation in organizational and program development that required human, material, and financial resource management to maintain client safety, well being and satisfaction, avert admissions to acute care, and identify new and relevant directions for community healthcare.


Implementation of a national nursing standards program.

At an annual nursing management conference of a multisystem hospital management firm, nursing executives expressed a need for developing nursing care standards. Because many of the hospitals were small or rural, they lacked some of the resources needed to develop such a program individually. Pooling resources so that all could benefit was an innovative and sensible approach. The authors describe the project that resulted in the development of a nation-wide standards program involving nearly 50 hospitals.


The Omaha System. A research-based model for decision making.

This article describes the value, diversity, and potential benefits of the Omaha System in generalizing and manipulating client, clinical, and financial data. The authors provide examples of its utility for day-to-day and long-range clinical and financial decision making in home and public health agencies, colleges of nursing, and ambulatory care centers throughout the United States and Canada.


Milestone Action Plans. Empowering nurses to manage care.

Confronted by continuing financial losses that could not be simply staunched by further reductions in the operations budget, a medical center implemented an innovative cost-cutting program that offered quick results and simplicity of design while assuring quality patient care. The authors describe the initiative known as Clinical Resource Management (CRM), which unites the expertise of physicians, nurses, and other care providers in a collaborative approach.


Characteristics of nursing practice models.

Are there differences among the nursing practice dimensions of the three major nursing practice models--team nursing, case management, and total patient care? The author, whose study found few differences, discusses reasons for the similarity among models and suggests approaches to designing future nursing practice models.


Collaboration in labor relations. A model for success.

Proliferation of bargaining units in currently unionized organizations will create new challenges and complexities for nurse executives. Although the literature abounds with strategies to prevent unionization, little had been presented on establishing and maintaining effective relations with bargaining units. The authors focus on currently unionized nursing practice environments and present a model for facilitating positive, cooperative relations between unions, the nursing profession, and the healthcare organization.


Fiscal and clinical evaluation of patient care. A case management model for the future.

The cost of healthcare within the United States continues to climb as does the number of individuals who have limited access to the healthcare system. By the year 2000, healthcare costs are predicted to comprise 15% of the gross national product. Over the last 10 years, the number of Americans who do not have financial protection from medical costs has risen dramatically. Presently, an estimated 35 million individuals have no insurance or other coverage.


Effects of policy manual reorganization on user proficiency.

This study compared the proficiency of nurses who located policies in a traditional, alphabetically arranged policy manual vs. a reorganized, indexed manual. Nurses were asked to locate policy statements that would resolve issues presented in three vignettes that were typical of the decisions nurses must regularly make. Answers were scored as correct or incorrect; time to respond and search strategies were also recorded. Data analyses show the overall superiority of the reorganized, indexed manual.


Demonstrating excellence in home care through Joint Commission accreditation.

Nurse administrators responsible for developing and managing home care delivery systems need to understand the eligibility criteria for accreditation, key components of the standards, survey, and accreditation decision process, and directions for the future including external recognition of accreditation and the use of an indicator monitoring system. The authors highlight the major components and benefits of the home care accreditation program of the Joint Commission on Accreditation of Healthcare Organizations, as well as how the nurse administrator may use accreditation as a valuable management tool.


Female nurse executives. Finally, at an advantage?

Discrimination, subtle and overt, from socialization and institutional forces, continues to keep nurse executives, most of whom are women, out of chief executive officer (CEO) positions. However, because of the women's movement, changing organizational forces, and shifting demographics, more nurse executives are likely to move into the ranks of CEOs. The authors explore the issues of managerial discrimination and indicate strategies that are beginning to open doors to female nurse executives who desire CEO positions.


Inner-city safety for home care providers.

For home health agencies to continue serving the elderly and the chronically ill in urban areas, providers must be protected from drugs, weapons, and violence--no easy task in today's environment. What recourse do agencies have short of refusing service? The author discusses what is required to assure safety for providers in the community and for agencies to meet their values, fulfill their missions, and keep healthcare affordable.


Obtaining services for HIV-positive patients.

Services needed for HIV-positive persons and the availability of these services were reported in the July/August 1990 issue of JONA. This article includes further information from the original study--an analysis of the factors in each reporting hospital and community that enabled or barred the development of services for HIV-positive persons. This information offers strategies to nurse executives for obtaining services in their own settings.


Recognizing excellence. Giving your AWE.

Nursing and hospital administrators have several methods of recognizing individual achievements. We developed an awards program to recognize excellence for an entire nursing unit. Our Award of Excellence uses rating factors to measure one unit against another. In a much heralded quarterly reception, strongly supported, funded, and attended by senior executives, the staff on the winning unit are complimented for their accomplishment. This program has reduced overtime, while improving productivity and quality of care.


Nurse-managed primary care. Tapping the rural community power base.

Involving community members into plans and projects is especially salient in initiating and maintaining nurse-managed centers. Nowhere is community involvement more crucial than in establishing a nursing practice in an isolated rural setting. The authors share their first-hand experiences in community interaction in establishing the state-funded health center.


Establishing an alternate level of care unit.

Timely discharge of patients is a major concern of hospitals due to the significant impact of reimbursement constraints. This presents special challenges for hospitals and their staff, who care for an increasing number of elderly patients who do not require acute care, but are waiting for placement in extended-care facilities. The authors describe development and economic impact of an alternate level of care unit, that provides an integrated program of services to address the needs of this patient population.


Energy expenditure and requirements in aging humans.

Although physical activity is frequently recommended for the elderly individual, its influence on energy intake and energy expenditure is unclear. The use of indirect calorimetry techniques and stable isotopes make it possible to examine the effects of physical activity on total daily energy expenditure and its components. In this review, the influence of physical activity on adaptive changes in energy intake, daily energy expenditure, resting metabolic rate and the energy expenditure of physical activity during nonexercising time was examined. Recent findings show that moderate physical activity can increase resting metabolic rate and energy intake in the elderly. Vigorous exercise, however, did not increase total daily energy expenditure because of a compensatory decline in physical activity during nonexercising time. These findings should prompt investigators to re-examine the influence of different levels of endurance exercise on total daily energy expenditure in an attempt to maximize the energy expending properties of physical exercise in older persons. A second objective was to examine the current status of methodology to predict energy requirements in older persons. Current recommendations for energy lack specificity and have not considered the influence of physical activity and body composition. Energy needs of older persons need to be re-examined based on the measurement of total daily energy expenditure. It will then be important to identify biological markers of total daily energy expenditure that take into account the variation in physical activity and body composition.


Protective effect of ascorbic acid on the breakdown of proteins exposed to hydrogen peroxide in chicken skeletal muscle.

Ascorbic acid is believed to protect cells from oxidative damage by reacting with oxygen-derived free radicals. We investigated whether ascorbic acid would affect the rate of breakdown of skeletal muscle proteins in extracts exposed to hydrogen peroxide. Ascorbic acid (20 mmol/L) alone had little or no effect on the rate of ATP-independent or ATP-dependent breakdown of proteins in chicken skeletal muscle. Pretreatment of chicken skeletal muscle extracts with 10 mmol/L H2O2 resulted in a complete loss of ATP-dependent proteolysis and a significant increase (14- to 15-fold) in the rate of ATP-independent protein breakdown. Ascorbic acid (20 mmol/L) did not prevent H2O2 (10 mmol/L) from inactivating the ATP-dependent proteolytic pathway in skeletal muscle. However, ascorbic acid (20 mmol/L) prevented the H2O2-induced increase in the ATP-independent proteolysis of endogenous muscle proteins. Ascorbic acid also slowed the rate of hydrolysis of exogenously added [3H]superoxide dismutase exposed to H2O2 and inhibited the enhanced degradation of [3H]lysozyme and H2O2-treated [3H]superoxide dismutase by the proteolytic systems exposed to H2O2. Thus ascorbic acid seems to inhibit the H2O2-induced increase in ATP-independent proteolysis 1) by preventing damage to proteins by H2O2 resulting in a decreased supply of substrates for the ATP-independent degradative system and 2) by preventing activation of the proteolytic enzymes that participate in the energy-independent degradation of H2O2-treated proteins.


Rat hepatic coenzyme A is redistributed in response to mitochondrial acyl-coenzyme A accumulation.

Coenzyme A without an acyl-thioester (CoASH) is required for numerous cellular reactions, and sequestration of CoASH as acyl-CoAs may impair metabolic function. Increased total CoA protects the cell from acyl-CoA accumulation, and enhanced CoA biosynthesis may represent a compensatory response in metabolic disease. To test the hypothesis that cellular CoA is redistributed from the cytosol to the mitochondria in response to mitochondrial acyl-CoA accretion, the subcellular distribution of hepatic CoA was determined by differential centrifugation and measurement of the mitochondrial marker enzyme citrate synthase. Liver from control, clofibrate-treated and hydroxycobalamin[c-lactam] (HCCL)-treated rats were used. Clofibrate increased total hepatic CoA concentration 2.2-fold, whereas HCCL (which causes inhibition of L-methylmalonyl-CoA mutase and consequent propionyl- and methylmalonyl-CoA accumulation) increased it threefold. However, clofibrate did not affect the percentage of total CoA in the mitochondria (control: 44 +/- 3%, clofibrate: 49 +/- 5%), and HCCL-treatment induced a marked redistribution of CoA into the mitochondria (HCCL: 78 +/- 8%). Redistribution of total CoA was also induced acutely by incubation of hepatocytes from control rats with 10 mmol/L propionate. Thus, redistribution of the cellular CoA pool can help maintain CoASH availability as mitochondrial acyl-CoA accumulation occurs and may be an important compensatory response to metabolic injury.


Copper-marginal and copper-deficient diets decrease aortic prostacyclin production and copper-dependent superoxide dismutase activity, and increase aortic lipid peroxidation in rats.

Agonist challenged aortic prostacyclin production was examined in copper-adequate, -marginal and -deficient rats fed AIN-based diets providing 6.7, 1.7 and 0.8 micrograms Cu/g, respectively. Aortic rings were incubated in Krebs-Henseleit salts, 10 mmol/L HEPES buffer, pH 7.4, 95%:5% O2:CO2, 37 degrees C, and equilibrated for 1 h. Equilibrated rings were challenged with buffer (basal), 273.0 nmol/L thrombin and angiotensin II at 84.6 pmol/L and 846.0 pmol/L. Prostacyclin production, determined at 10 minutes by RIA as 6-keto prostaglandin F1 alpha, in basal and 84.6 pmol/L angiotensin II ring incubations was significantly reduced by 28 to 48% in copper-deficient rats. With thrombin or 846.0 pmol/L angiotensin II prostacyclin production was significantly reduced by 18 to 55% in copper-marginal and copper-deficient rats. Copper-dependent superoxide dismutase activity was significantly depressed by 30 and 57% in aortae of copper-marginal and copper-deficient rats. Lipid peroxidation, estimated by the thiobarbituric acid test, was significantly increased by 85% in copper-deficient rats, with a nonsignificant 40% increase in aortae from copper-marginal rats. The results suggest that the decreases in aortic prostacyclin production in aortae from both copper-deficient and copper-marginal rats are associated, in a dose-dependent manner, with copper-dependent superoxide dismutase depression and increases in aortic lipid peroxidation.


Plasma esterase-1 (ES-1) activity in rats is influenced by the amount and type of dietary fat, and butyryl cholinesterase activity by the type of dietary fat.

In previous work, we studied, under conditions of ad libitum food consumption, the effect of amount and type of dietary fat on plasma esterase-1 (ES-1) and butyryl cholinesterase activity in rats. This was done by the isoenergetic replacement of dietary fat by carbohydrates or by another fat source. The observed change in enzyme activity could theoretically be determined by either the dietary omission or the addition or by the combination. In the present work, we studied under restricted feeding conditions the effect of supplemental energy in various forms to determine the effect of the supplement alone. Supplemental coconut fat, but not isoenergetic amounts of either glucose or casein, raised plasma ES-1 activity. None of these supplements influenced butyryl cholinesterase activity. In a second experiment, we demonstrated that the ES-1 enhancing effect of supplemental coconut fat also occurred with fish oil, whereas the stimulatory effects of olive oil and corn oil were less pronounced. Supplemental fish oil, but not the three other fats, significantly reduced the depression in butyryl cholinesterase activity. Plasma cholesterol concentration was negatively associated with butyryl cholinesterase activity, but was not related to ES-1 activity. The two esterases were not correlated with plasma triglyceride concentration. We conclude that both the amount and type of fat in the diet of rats have specific influences on plasma ES-1 activity and that butyryl cholinesterase activity is affected by the type of fat.


Copper and selenium deficiencies do not enhance the cardiotoxicity in rats due to chronic doxorubicin treatment.

This study tests the hypothesis that Cu and Se deficiencies enhance doxorubicin-induced cardiotoxicity and anemia. Male Sprague-Dawley rats (n = 48) were fed Cu and Se-adequate (+Cu+Se), Cu-deficient (-Cu), Se-deficient (-Se) or Cu and Se-deficient (-Cu-Se) diets for 5.5 wk. Doxorubicin (4 mg/kg body wt) or saline was administered once weekly for the last 4 wk of the study. Copper deficiency was confirmed by 79% lower liver Cu, 67% lower liver Cu,Zn superoxide dismutase (Cu,Zn SOD) activity and 76% lower erythrocyte Cu,Zn SOD activity. Selenium deficiency was confirmed by 90% lower liver glutathione peroxidase activity. Rats fed the -Cu diet had greater reductions in hematocrit than did those fed the +Cu diet after administration of doxorubicin. Doxorubicin, Cu deficiency and Se deficiency all produced electrocardiographic abnormalities and ultrastructural anatomical lesions. However, the dietary deficiencies did not enhance doxorubicin-induced cardiotoxicity. Doxorubicin, but not Cu or Se deficiency, raised lipid peroxidation 16% in liver (P < 0.01) and 18% in heart (not significant). These data suggest that the cardiomyopathies caused by doxorubicin and Cu and Se deficiencies have some similarities, but cardiac changes may be related to mechanisms other than lipid peroxidation.