Tardive dyskinesia as a result of long-term prochlorperazine use.

Prochlorperazine is a centrally acting dopamine receptor antagonist that is most commonly used for the treatment of nausea and vomiting. Like many dopamine antagonists, prochlorperazine has the ability to induce extrapyramidal reactions in susceptible patients. Rarely, however, have cases of tardive dyskinesia been caused by the long-term use of this agent. We report the case of a patient who used prochlorperazine for a prolonged period and, during hospital admission, was found to have a new movement disorder. Alternative antiemetics that do not pose a risk of movement disorders, such as ondansetron and granisetron, are readily available and are efficacious.

Electron beam intraoperative radiation therapy for pediatric neoplasms.

BACKGROUND: Intraoperative radiation therapy (IORT) has potential advantages over conventional external beam radiation in that a single large dose is delivered to the tumor and its regional bed at the time of surgical exploration. The therapeutic ratio is enhanced by direct tumor visualization, precise treatment volume, and exclusion of normal organs. In childhood, local tumor control is critical for lesions that cannot be totally excised or residual disease not ablated by systemic therapy. METHODS: During the past decade, the authors evaluated IORT in pediatric patients with unresectable or recurrent tumors. Fifty-nine patients were treated, 48 for advanced malignant disease and 11 for histologically benign but locally aggressive tumors. Sixty-four operations were performed, during which 84 separate radiation fields were used. High energy electrons at 5-11 MeV were delivered at a dose of 1000-1700 cGy to a tissue depth of 0.5-3 cm. RESULTS: Of 25 children with advanced neuroblastoma, 15 were alive 14-104 months (mean, 51 months) after treatment. The survival of all patients with solid malignancies was 63%. Local tumor control was achieved in 75% of children with cancer and 91% of those with benign tumors. Complications of IORT at the doses used were trivial. CONCLUSIONS: Electron beam therapy can be safely and efficiently delivered to young patients during operations intended to treat the primary tumor. The outcome achieved for overall survival and local control of the primary tumor is encouraging, and an acceptable complication rate during intermediate to long-term follow-up has been noted.

Right atrial catheters in pediatric oncology: a patient/parent questionnaire study.

Venous access devices are an option offered to pediatric oncology patients to make their frequent blood sampling and intravenous therapy more tolerable. To determine the advantages and disadvantages of using these devices, a study comparing Mediport and Broviac catheters was conducted from August 1985 to August 1987 at The Children's Hospital, Denver, Colorado. This report will analyze results of the patient-parent acceptance questionnaire employed in that study. Overall, both the patients and their parents were very positive about the devices. Daily care of the Broviac and pain associated with accessing the Mediport were the only uniformly negative factors we encountered. These problems became unimportant when compared to the advantage of eliminating peripheral venipuncture.

Comparison of totally implanted reservoirs with external catheters as venous access devices in pediatric oncologic patients.

Long term venous access devices have become an important part of the standard care for children with malignant diseases requiring chemotherapy. A prospective nonrandomized study was conducted between January 1985 and January 1987 examining complications, child and parental acceptance and costs between totally implantable venous access devices (ports) and externally exiting catheters. Fifty ports were placed in 49 patients who had a median age of ten years; median implant time was 350 days. Forty-one catheters were placed in 39 patients who had a median age of eight years; median implant time was 365 days. Both devices provided equivalent venous access. Although catheters were initially less expensive, the cost for both devices was comparable by the six month point. Beyond this time, an increasing savings was realized when the port was used. Catheter device complications occurred 14 times compared with seven with ports (p less than 0.02). There were 15 infectious complications with catheters compared with seven with ports (p less than 0.01). Child and parental acceptance questionnaires indicated that the ports were easier to care for and more readily accepted in children older than 11 years than were catheters (p less than 0.001). Totally implanted reservoirs are effective alternatives to external catheters for venous access in children with cancer.

The effect of contralateral disease on carotid Doppler frequency.

Continuous-wave Doppler frequency analysis is one standard of noninvasive evaluation for stenotic carotid disease. Interpretation is most commonly based on frequency recorded at the site of stenosis. If flow velocity is increased because of contralateral disease, this criterion may overstate the degree of stenosis. To investigate this, three centers contributed 167 patients to a study of carotid Doppler frequency analysis. Each patient underwent bilateral carotid studies by a standard protocol with use of continuous-wave 5 MHz Doppler probe. There were 309 patent and 25 occluded internal carotids seen on subsequent angiographs. Each patient side was categorized by the severity of ipsilateral disease (less than 45%, 45% to 70%, 71% to 99%, occlusion) and then subgrouped by contralateral disease. For all carotid arteries, the optimal peak frequency to detect 45% or more stenosis was 5500 Hz, with an overall accuracy of 92.2%. Within the three classifications of ipsilateral stenosis, a trend was noted that related increasing peak frequency to greater degrees of contralateral disease. This was most apparent when the contralateral internal carotid artery was occluded. Of all false-positive errors, 43% were accounted for by this subset that represented 15% of the total population. For the 25 patients with occlusion opposite a stenosis, the 5500 Hz cutoff of Doppler peak frequency yielded only 76% accuracy; an ROC curve showed that a cutoff value of 8500 Hz improved overall accuracy to 92% for these patients. By applying two cutoff criteria--5500 Hz for those with patent contralateral internal carotids and 8500 Hz for those in whom a contralateral Doppler signal was not detected--the overall accuracy for all patients improved to 93.3%. It is concluded that contralateral occlusion affects Doppler peak frequency by increasing the velocity in the companion carotid artery, whereas severe contralateral stenosis did not result in a consistent pattern of increased velocity.

Effect of growth phase on phospholipid biosynthesis in Saccharomyces cerevisiae.

The effect of growth phase on the membrane-associated phospholipid biosynthetic enzymes CDP-diacylglycerol synthase, phosphatidylserine synthase, phosphatidylinositol synthase, and the phospholipid N-methyltransferases in wild-type Saccharomyces cerevisiae was examined. Maximum activities were found in the exponential phase of cells grown in complete synthetic medium. As cells entered the stationary phase of growth, the activities of the CDP-diacylglycerol synthase, phosphatidylserine synthase, and the phospholipid N-methyltransferases decreased 2.5- to 5-fold. The subunit levels of phosphatidylserine synthase and the cytoplasmic-associated enzyme inositol-1-phosphate synthase were not significantly affected by the growth phase. When grown in medium supplemented with inositol-choline, cells in the exponential phase of growth had reduced CDP-diacylglycerol synthase, phosphatidylserine synthase, and phospholipid N-methyltransferase activities, with repressed subunit levels of phosphatidylserine synthase and inositol-1-phosphate synthase compared with cells grown without inositol-choline. Enzyme activity levels remained reduced in the stationary phase of growth of cells supplemented with inositol-choline. The phosphatidylserine synthase and inositol-1-phosphate synthase subunit levels, however, were depressed. Phosphatidylinositol synthase (activity and subunit) was not affected by growth in medium supplemented with or without inositol-choline or the growth phase of the culture. The phospholipid composition of cells in the exponential and stationary phase of growth was also examined. The phosphatidylinositol to phosphatidylserine ratio doubled in stationary-phase cells. The phosphatidylcholine to phosphatidylethanolamine ratio was not significantly affected by the growth phase of cells.

The membrane-associated enzyme phosphatidylserine synthase is regulated at the level of mRNA abundance.

To precisely define the functional sequence of the CHO1 gene from Saccharomyces cerevisiae, encoding the regulated membrane-associated enzyme phosphatidylserine synthase (PSS), we subcloned the original 4.5-kilobase (kb) CHO1 clone. In this report a 2.8-kb subclone was shown to complement the ethanolamine-choline auxotrophy and to repair the defect in the synthesis of phosphatidylserine, both of which are characteristic of cho1 mutants. When this subclone was used as a hybridization probe of Northern and slot blots of RNA from wild-type cells, the abundance of a 1.2-kb RNA changed in response to alterations in the levels of the soluble phospholipid precursors inositol and choline. The addition of inositol led to a 40% repression of the 1.2-kb RNA level, while the addition of choline and inositol led to an 85% repression. Choline alone had little repressive effect. The level of 1.2-kb RNA closely paralleled the level of PSS activity found in the same cells as determined by enzyme assays. Disruption of the CHO1 gene resulted in the simultaneous disappearance of 1.2-kb RNA and PSS activity. Cells bearing the ino2 or ino4 regulatory mutations, which exhibit constitutively repressed levels of a number of phospholipid biosynthetic enzymes, had constitutively repressed levels of 1.2-kb RNA and PSS activity. Another regulatory mutation, opi1, which causes the constitutive derepression of PSS and other phospholipid biosynthetic enzymes, caused the constitutive derepression of the 1.2-kb RNA. When cho1 mutant cells were transformed with the 2.8-kb subclone on a single-copy plasmid, the 1.2-kb RNA and PSS activity levels were regulated in a wild-type fashion. The presence of the 2.8-kb subclone on a multicopy plasmid, however, led to the constitutive overproduction of 1.2-kb RNA and PSS in cho1 cells.

Quantitative analysis of continuous-wave Doppler spectral broadening for the diagnosis of carotid disease: results of a multicenter study.

This article reports the results of a multicenter study that compares 333 frequency analysis studies with the continuous-wave Doppler method with angiography. With receiver operating characteristic curves, the study documents the accuracy of the Doppler technique for the diagnosis of extracranial carotid arterial stenosis greater than 45% diameter reduction. It confirms the accuracy of the measurement of the maximal peak Doppler frequency and, in addition, shows that quantitative analysis of the instantaneous Doppler spectrum at peak systole by the measurement of the spectral broadening index is of diagnostic value. Likelihood ratios have been calculated with the use of curve-fitting techniques and it has been demonstrated how both the peak frequency and the spectral broadening index can be used together to improve the certainty of diagnosis. It is concluded that the probability that an individual patient has significant carotid arterial disease can be determined with the measurements of peak frequency and spectral broadening index from the continuous-wave Doppler spectral waveform.

Regulation of phosphatidylserine synthase from Saccharomyces cerevisiae by phospholipid precursors.

The addition of ethanolamine or choline to inositol-containing growth medium of Saccharomyces cerevisiae wild-type cells resulted in a reduction of membrane-associated phosphatidylserine synthase (CDPdiacylglycerol:L-serine O-phosphatidyltransferase, EC 2.7.8.8) activity in cell extracts. The reduction of activity did not occur when inositol was absent from the growth medium. Under the growth conditions where a reduction of enzyme activity occurred, there was a corresponding qualitative reduction of enzyme subunit as determined by immunoblotting with antiserum raised against purified phosphatidylserine synthase. Water-soluble phospholipid precursors did not effect purified phosphatidylserine synthase activity. Phosphatidylserine synthase (activity and enzyme subunit) was not regulated by the availability of water-soluble phospholipid precursors in S. cerevisiae VAL2C(YEp CHO1) and the opi1 mutant. VAL2C(YEp CHO1) is a plasmid-bearing strain that over produces phosphatidylserine synthase activity, and the opi1 mutant is an inositol biosynthesis regulatory mutant. The results of this study suggest that the regulation of phosphatidylserine synthase by the availability of phospholipid precursors occurs at the level of enzyme formation and not at the enzyme activity level. Furthermore, the regulation of phosphatidylserine synthase is coupled to inositol synthesis.

Phosphatidylinositol synthase from Saccharomyces cerevisiae. Reconstitution, characterization, and regulation of activity.

Purified membrane-associated phosphatidylinositol synthase (CDP diacylglycerol:myo-inositol 3-phosphatidyltransferase, EC 2.7.8.11) from Saccharomyces cerevisiae was reconstituted into unilamellar phospholipid vesicles. Reconstitution of the enzyme was performed by removing detergent from an octylglucoside/phospholipid/Triton X-100/enzyme mixed micelle mixture by Sephadex G-50 superfine column chromatography. The average diameter of the vesicles was 40 nm and chymotrypsin treatment of intact vesicles indicated that over 90% of the reconstituted enzyme had its active site facing outward. The enzymological properties and reaction mechanism of reconstituted phosphatidylinositol synthase were determined in the absence of detergent. The reconstituted enzyme was used as a model system to study the regulation of activity. Phosphatidylinositol synthase was constitutive in wild type cells grown in the presence of water-soluble phospholipid precursors as determined by enzyme activity and immunoblotting. Reconstituted enzyme was not effected by water-soluble phospholipid precursors or nucleotides. Maximum activity was found when the enzyme was reconstituted into phosphatidylcholine: phosphatidylethanolamine: phosphatidylinositol: phosphatidylserine vesicles. Phosphatidylserine stimulated reconstituted activity, suggesting that the local phospholipid environment may regulate phosphatidylinositol synthase activity.

Frequency, severity, and physiologic importance of carotid siphon lesions.

Atherosclerotic stenosis of the intracranial portion of the internal carotid artery (SIPHON) may be the cause of neurologic symptoms. The frequency and severity of these lesions were studied in 226 vessels subjected to conventional two-plane carotid angiography, and the impact of sequential or tandem lesions on cerebral flow was assessed in the 167 arteries from this group that also underwent Gee oculoplethysmography (OPG-Gee), a commonly accepted indicator of the physiologic importance of internal carotid stenosis. Atherosclerotic involvement of the SIPHON was present in 46% (103/226) of the vessels studied, including six total occlusions, 11 severe stenoses (severe, 80% to 99% area reduction [AR]), 27 moderate stenoses (moderate, 50% to 79% AR), 40 mild stenoses (mild, 10% to 49% AR), and 19 instances of mural disease (MUR). This was compared with a 73% rate (166 of 226) of proximal internal carotid artery (PICA) stenosis in the neck, including six to 43 severe, 29 moderate, 50 mild, and 38 MUR. There was little correlation (r = 0.33) between the degree of angiographic stenosis in the PICA and the SIPHON. All of the totally occluded arteries had a positive OPG-Gee, whereas a positive study was noted in only 6% (7 of 109) of the arteries with less than moderate stenosis in the PICA. Twenty-one vessels had moderate stenosis of the PICA. Eight of these arteries had an associated moderate or severe lesion in the SIPHON, and seven of eight (88%) had a positive OPG-Gee. The remaining 13 of this subset had had a normal or mildly diseased SIPHON, and 12 of 13 (92%) had a normal OPG-Gee.(ABSTRACT TRUNCATED AT 250 WORDS)

Cysteine proteinase procoagulant from amnion-chorion.

Various coagulation abnormalities are associated with pregnancy. Several investigators have suggested that there may be a unique procoagulant associated with amniotic tissue and fluid. We identified a cysteine proteinase from malignant tissue, cancer procoagulant, and had reason to believe a similar proteinase may be present in amniotic tissue. Amniotic fluid and extracts of amnion-chorion were purified by immunoaffinity chromatography with an antibody that was developed to cancer procoagulant antigen. The purified amnion-chorion procoagulant initiated clotting in normal and factor VII-deficient citrated human plasma and directly activated pure human factor X in a two-stage clotting assay. It was inhibited by 1 mmol/L of iodoacetamide and 0.1 mmol/L of HgCl2, and the procoagulant activity was activated by 10 mmol/L of KCN; these are classic properties of cysteine proteinases. The pure amnion-chorion procoagulant had the same mol wt and immunologic determinants as cancer procoagulant from rabbit V2 carcinoma, as determined by crossed immunodiffusion, suggesting that the same or very similar proteins were associated with both tissues. Thus, this procoagulant may be derived from both undifferentiated and dedifferentiated cells.

Incidence of recurrent or residual stenosis after carotid endarterectomy.

The incidences of recurrent and residual stenosis after carotid endarterectomy have been controversial. Duplex scanning has recently provided an accurate noninvasive method of quantifying areas of arterial narrowing, and this technique was used in 122 postendarterectomy vessels from 71 men and 35 women with a mean age of 65.2 years. The average time interval between operation and scanning was 26.3 months (range 1 month to 11.76 years). Postoperative examination of the internal carotid artery revealed no stenosis in 78 vessels, less than 50 percent area reduction in 17 vessels, 50 to 75 percent stenosis in 11 vessels, more than 75 percent area reduction in 9 vessels, and total occlusion in 7 vessels. Thus, 22 percent of the vessels (27 of 122) had total occlusion or more than 50 percent area reduction after carotid endarterectomy. This is a higher rate of recurrent stenosis than was diagnosed by oculoplethysmography, where 7 of 52 vessels (13 percent) had a positive oculoplethysmogram after operation. These data show that the reported incidence of residual or recurrent stenosis after carotid endarterectomy is heavily dependent on the testing method used. Duplex scanning documents a 22 percent frequency of residual or recurrent stenosis, a figure higher than has been reported with less sensitive tests.

Enzymatic detection of phospholipid biosynthetic enzymes after electroblotting.

The membrane-associated enzymes phosphatidylinositol synthase (CDPdiacylglycerol:myo-inositol 3-phosphatidyltransferase; EC 2.7.8.11) and phosphatidylserine synthase (CDPdiacylglycerol:L-serine O-phosphatidyltransferase; EC 2.7.8.8) from Saccharomyces cerevisiae were detected enzymatically after sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electroblotting. Enzyme activities were measured on nitrocellulose blots by using pure enzyme preparations as well as Triton X-100-solubilized membranes. Phosphatidylinositol synthase activity migrated to Mr 34,000, and phosphatidylserine synthase activity migrated to Mr 23,000.

Training apartment in community for spinal cord injured patients: a model.

This paper describes the setting of a spinal cord injury (SCI) training apartment in the community. The purposes of its location in the community as a predischarge strategy are to regain confidence in the skills relearned to live independently, to initiate positive interpersonal relationships between individuals and family or other significant caretaker persons after the separation due to long hospitalization, to aid the patient and the rehabilitation team in determining the need for further rehabilitation, and to reduce length of hospitalization. The management and accountability, physical design and layout of the apartment, and patient assignments are described. All of the 32 patients were discharged to noninstitutional settings, 30 to homes and 2 to residential schools. After 15 months none required readmission for preventable complications.