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Biomedical subjects

J A Snyder

Publications and source records attributed to J A Snyder.

At least 19 recordsLinked to original sources

Survival of implanted fetal dopamine cells and neurologic improvement 12 to 46 months after transplantation for Parkinson's disease.

BACKGROUND AND METHODS: Patients with Parkinson's disease tend to have a reduced response to levodopa after 5 to 20 years of therapy, with "on-off" fluctuations consisting of dyskinesia alternating with immobility. In an effort to modify the motor disability of advanced Parkinson's disease, we implanted embryonic mesencephalic tissue containing dopamine cells into the caudate and putamen of seven patients. Two patients received unilateral grafts in the caudate and the putamen on the side opposite the side with worse symptoms. Five patients received bilateral grafts implanted in the putamen only. In six of the seven patients, the fetal tissue was obtained from a single embryo with a gestational age of seven to eight weeks. The tissue was injected by means of 10 to 14 needle passes. There were no surgical complications. Four of the seven patients underwent immunosuppression with cyclosporine and prednisone. RESULTS: All patients reported improvement according to the Activities of Daily Living Scale when in the on state 3 to 12 months after surgery (P < 0.01). Neurologic examination according to the Unified Disease Rating Scale showed that five of the seven patients improved when in the on state six months after surgery. The mean group Hoehn-Yahr score improved from 3.71 to 2.50 (P < 0.01). Computer and videotape testing in the home supported these findings. Fluctuations in clinical state were moderated, and periods of dyskinesia and off episodes were shorter and less severe than before implantation. Drug doses were reduced by an average of 39 percent (P < 0.01; maximum, 58 percent). The results of clinical evaluation and fluorodopa positron-emission tomography in one patient were compatible with transplant survival for as long as 46 months. Both immunosuppressed and nonimmunosuppressed patients improved. CONCLUSIONS: Fetal-tissue implants appear to offer long-term clinical benefit to some patients with advanced Parkinson's disease.

Activities of Daily Living

Specialized services for psychiatric patients in the emergency department.

The care of the psychiatric patient in the emergency department offers yet another opportunity for emergency nurses to draw on specialty nursing resources or to create expanded roles for emergency practitioners themselves. As our emergency departments continue to encounter increasing numbers of patients, the need for concise and expeditious psychiatric consultation protocols becomes even more clear.

Emergency Nursing

UV-microbeam irradiations of the mitotic spindle: spindle forces and structural analysis of lesions.

Mitotic PtK1 spindles were UV irradiated (285 nm) during metaphase and anaphase between the chromosomes and the pole. The irradiation, a rectangle measuring 1.4 x 5 microns parallel to the metaphase plate, severed between 90 and 100% of spindle microtubules (MTs) in the irradiated region. Changes in organization of MTs in the irradiated region were analyzed by EM serial section analysis coupled with 3-D computer reconstruction. Metaphase cells irradiated 2 to 4 microns below the spindle pole (imaged by polarization optics) lost birefringence in the irradiated region. Peripheral spindle fibers, previously curved to focus on the pole, immediately splayed outwards when severed. We demonstrate via serial section analysis that following irradiation the lesion was devoid of MTs. Within 30 s to 1 min, recovery in live cells commenced as the severed spindle pole moved toward the metaphase plate closing the lesion. This movement was concomitant with the recovery of spindle birefringence and some of the severed fibers becoming refocused at the pole. Ultrastructurally we confirmed that this movement coincided with bridging of the lesion by MTs presumably growing from the pole. The non-irradiated half spindle also lost some birefringence and shortened until it resembled the recovered half spindle. Anaphase cells similarly irradiated did not show recovery of birefringence, and the pole remained disconnected from the remaining mitotic apparatus. Reconstructions of spindle structure confirmed that there were no MTs in the lesion which bridged the severed spindle pole with the remaining mitotic apparatus. These results suggest the existence of chromosome-to-pole spindle forces are dependent upon the existence of a MT continuum, and to a lesser extent to the loss of MT initiation capacity of the centrosome at the metaphase/anaphase transition.

Anaphase

Evaluation of female urinary incontinence.

The use of urodynamic testing must be selective and based on the particular patient's complaints. In today's cost-conscious health care environment, a diagnosis based on one or two tests is preferable to exposing each patient to the full battery of available tests. For most patients, a cystometrogram and voiding cystourethrogram can confirm a variety of clinical suspicions. A cystometrogram best indicates how the bladder is behaving during filling. The voiding cystourethrogram allows the physician to observe the bladder and urethra during voiding and offers an excellent view of the anatomic relations of the urologic organs in the pelvis. The other important benefit of urodynamics is the objective data made available in hardcopy as a baseline study to be utilized for comparison in the future. The normal sequence of testing is a noninvasive uroflow study to determine the baseline flow rate. The postvoiding residual volume of urine is then determined. A cystometrogram and electromyography can then be done, the latter if there is a suggestion of neurologic disease or if otherwise indicated to determine bladder behavior on filling. Variations that are helpful when a patient fails to have a bladder contraction include having the patient in an upright or seated position during the test. A bethanechol supersensitivity test may be indicated as well. The urethral pressure profile may be done as the catheter is withdrawn and the bladder is already filled. The filled invasive flow rate can then be compared with the free flow rate. Sometimes, one of these rates is abnormal, and there is a question about whether the abnormality is real. The residual urine volume can be determined by subtracting the volume the patient voids from the filling volume. In the end, the key to urodynamic evaluation is the interpretation of the test, which should be made only by the individual actually performing the test. It truly is necessary for the physician to be there in person. Selective use of urodynamics can target an appropriate treatment for most patients. The female patient who complains of incontinence in whom the history suggests detrusor instability may benefit from a trial of cholinolytic therapy if no anatomic defect is present. In this type of patient, a surgical procedure may not be of benefit, whereas the cholinolytic therapy probably will work. This is a good reason for always choosing the appropriate urodynamic tests for evaluating and planning treatment for patients with urinary incontinence.

Female

Post-nephrolithotomy chyluria.

Percutaneous nephrolithotomy has proved to be a cost-effective, safe and expeditious means of renal calculus removal since its introduction in the late 1970s. The inherent risks and complications of this procedure have been well documented but less common complications continue to surface as case selection becomes increasingly more difficult. We report a case of chyluria after percutaneous nephrolithotomy. The patient recovered completely after treatment with total parenteral nutrition and required no further intervention. The etiology as well as the treatment of this previously unreported complication following percutaneous nephrolithotomy is addressed.

Chyle

UV microbeam irradiations of the mitotic spindle. II. Spindle fiber dynamics and force production.

Metaphase and anaphase spindles in cultured newt and PtK1 cells were irradiated with a UV microbeam (285 nM), creating areas of reduced birefringence (ARBs) in 3 s that selectively either severed a few fibers or cut across the half spindle. In either case, the birefringence at the polewards edge of the ARB rapidly faded polewards, while it remained fairly constant at the other, kinetochore edge. Shorter astral fibers, however, remained present in the enlarged ARB; presumably these had not been cut by the irradiation. After this enlargement of the ARB, metaphase spindles recovered rapidly as the detached pole moved back towards the chromosomes, reestablishing spindle fibers as the ARB closed; this happened when the ARB cut a few fibers or across the entire half spindle. We never detected elongation of the cut kinetochore fibers. Rather, astral fibers growing from the pole appeared to bridge and then close the ARB, just before the movement of the pole toward the chromosomes. When a second irradiation was directed into the closing ARB, the polewards movement again stopped before it restarted. In all metaphase cells, once the pole had reestablished connection with the chromosomes, the unirradiated half spindle then also shortened to create a smaller symmetrical spindle capable of normal anaphase later. Anaphase cells did not recover this way; the severed pole remained detached but the chromosomes continued a modified form of movement, clumping into a telophase-like group. The results are discussed in terms of controls operating on spindle microtubule stability and mechanisms of mitotic force generation.

Anaphase

The effect of air abrasive polishing on blood pH and electrolyte concentrations in healthy mongrel dogs.

The recent re-emergence of air abrasive polishing as an adjunct to professional tooth cleaning has been accompanied by a substantial amount of research. Most of this research has focused on the efficacy of the Prophy-Jet and similar devices in the removal of plaque and stain and on the effects of such devices on restorative materials and the various hard structures of the tooth. Little attention has been paid to the effects of mucosal absorption of the sodium bicarbonate in the polishing abrasive. The purpose of this study was to measure any changes in arterial blood chemistry resulting from the use of the Prophy-Jet. The values for pH, sodium, and bicarbonate, as well as other electrolytes, were measured in 10 dogs over a 2 hour period following a 5 minute timed use of the Prophy-Jet. Of all the parameters examined, only the potassium concentration showed a statistically significant change, and the magnitude of this change was not felt to be clinically significant. The pH and concentrations of sodium and bicarbonate remained essentially unchanged with the use of the Prophy-Jet.

Air

Selective reduction of anaphase B in quinacrine-treated PtK1 cells.

Quinacrine, an acridine derivative which competitively binds to ATP binding sites, has previously been shown to cause the reorganization of metaphase spindle microtubules (MTs) due to changes in interactions of non-kinetochore microtubules (nkMTs) of opposite polarity (Armstrong and Snyder: Cell Motil. Cytoskeleton 7:10-19, 1987). In the study presented here, mitotic PtK1 cells were treated in early anaphase with concentrations of quinacrine ranging from 2 to 12 microM to determine energy requirements for chromosome motion. The rate and extent of chromosome-to-pole movements (anaphase A) were not affected by these quinacrine treatments. The extent of anaphase B (kinetochore-kinetochore separation) was reduced with increasing concentrations of quinacrine. Five micromolar quinacrine reduced the extent of kinetochore-kinetochore separation by 20%, and addition of 12 microM quinacrine reduced the kinetochore-kinetochore separation by 40%. To determine the role of nkMTs in anaphase spindle elongation, quinacrine-treated metaphase cells were treated with hyperosmotic sucrose concentrations, and spindle elongation was measured (Snyder et al.: Eur J. Cell Biol. 39:373-379, 1985). Metaphase cells treated with 2-10 microM concentrations of quinacrine for 2-5 min reduced spindle lengths by 10-50% prior to 0.5 M sucrose treatment for 5 min. This treatment showed a significant reduction in the ability of sucrose to induce spindle elongation in cells pretreated with quinacrine. As spindle length and birefringence was reduced by quinacrine treatment, sucrose-induced elongation was concomitantly diminished. These data suggest that quinacrine-sensitive linkages are necessary for anaphase B motions. Reduction in these linkages and/or MT length in the nkMT continuum may reduce the ability of the nkMTs to hold compression at metaphase. This form of energy is thought to drive a significant proportion of normal anaphase B in PtK1 cells and sucrose-induced metaphase spindle elongation.

Anaphase

Vaginal wall sling.

We describe a new technique for the treatment of urinary incontinence due to intrinsic sphincteric damage in which a sling constructed from vaginal wall is used to provide compression and support of the urethra. A rectangular island of in situ anterior vaginal wall underlying the urethra and bladder neck is developed, the 4 corners are anchored with polypropylene sutures and a ligature carrier is used to transfer the sutures to a suprapubic location. An anterior vaginal wall flap proximal to the island is advanced to cover the island. When the sutures are tied the resulting sling will support the urethra and increase urethral resistance by compression, restoring continence. The advantages are its simplicity, need for only a small incision, short operative time and hospital stay, and reliance on healthy, well vascularized, in situ tissue. Continence has been achieved in 29 of 32 cases. All patients voided spontaneously except for those with neuropathic urethral incompetence who required self-catheterization.

Adult

Induction of random microtubule polymerization in cold and drug-treated PtK1 cells following hyperosmotic shock treatment.

The effects of hypertonic sucrose on spindle and interphase microtubule (MT) arrays of PtK1 cells were investigated by incubating cells in complete culture medium at 4 degrees or 37 degrees C, with or without hypertonic sucrose, nocodazole or vinblastine (VLB). Results from anti-tubulin immunofluorescence showed that sucrose-induced alterations of spindle morphology seen at 37 degrees C did not occur at cold temperatures, but cold-induced MT loss was diminished. Application of warm hypertonic sucrose following depolymerization of MTs by nocodazole or cold resulted in the formation of a "feltwork" of randomly oriented, short MTs throughout the cytoplasm. These results, and those obtained substituting VLB for nocodazole, suggest that the effects of sucrose depend on the cytoplasmic concentration of soluble tubulin and support the hypothesis that osmotic factors are involved in effects of hypertonic sucrose on MT organization.

Animals

Effect of metabolic inhibitors on sucrose-induced metaphase spindle elongation and spindle recovery.

Hyperosmotic sucrose treatment of metaphase PtK-1 cells has been shown to produce a reversible concentration-dependent effect on spindle elongation linked to a functional alteration in the connection of the chromosome to the spindle (Pover et al.: European Journal of Cell Biology 39:366-372, 1985). Spindle elongation, similar to that which occurs at anaphase B, is thought to be driven by the compression stored in the form of microtubule curvature in the nonkinetochore (nkMT) population of microtubules at metaphase (Snyder et al.: European Journal of Cell Biology 35:62-69, 1984 and 39:373-379, 1985). Addition of metabolic inhibitors to Ham's F-12 salts with deoxyglucose (D/F-12 medium) containing 0.4 M sucrose and 1 mM DNP does not within statistical error affect the rate and extent of sucrose-induced spindle elongation; rates and extents are 60-75% of normal anaphase B motions. Electron microscopic analysis of metaphase cells treated with D/F-12 medium and 0.4 M sucrose with 1 mM DNP demonstrates that spindle microtubules lose curvature and become straight in appearance, typical of microtubule organization in untreated anaphase cells. Sucrose-treated cells released into D/F-12 medium show a rapid reduction in spindle length; however, cells treated with either 0.4 M sucrose or 0.4 M sucrose and 1 mM DNP-containing D/F-12 medium and released into DNP-containing D/F-12 medium do not exhibit a significant reduction in spindle length. Electron microscopic analysis links changes in spindle length with microtubule/kinetochore associations. These data suggest that energy required for the initial phases of spindle elongation during anaphase is preloaded into the mitotic spindle by metaphase and does not require additional energy to be expressed as examined by sucrose-induced spindle elongation in the presence of metabolic inhibitors. Second, energy is required to make or maintain (or both) functional chromosome associations with the spindle as measured by reduction in spindle length following sucrose removal.

Animals

Mechanical extraction of stones with rigid ureteroscopes.

Ureteroscopy, once the province of experienced endourologists, is now being done routinely by nearly all urologists. Thorough preoperative evaluation, proper selection of instruments, and gentle manipulation will lead to stone retrieval with minimal sequelae.

Endoscopes

Quinacrine-induced changes in mitotic PtK1 spindle microtubule organization.

Quinacrine, an acridine derivative which competitively binds to ATP binding sites, has been used to study the role of ATP requiring molecules in microtubule organization in mitotic PtK1 cells. Brief treatments of metaphase cells with concentrations of quinacrine ranging from 2 to 10 microM decreased spindle length and birefringence in a concentration-dependent manner. With either increasing quinacrine concentrations or duration of treatment, metaphase cells demonstrated a specific reorganization of spindle microtubules. Both polarization and electron microscopy showed a substantial loss of non-kinetochore spindle microtubules with an increase in astral microtubules: this was particularly evident in the region adjacent to the spindle domain. Addition of millimolar concentrations of dinitrophenol to quinacrine-containing medium did not potentiate the response of metaphase cells to quinacrine treatment. Time-lapse video analysis demonstrated that the astral microtubules are the result of reorganization of spindle microtubules. These data suggest that functional ATP binding sites are required to maintain stable interactions between microtubules and that these interactions are responsible for maintaining the bowed configuration of non-kinetochore spindle microtubules which are under compression at metaphase.

Adenosine Triphosphate

Staghorn calculi: endourologic management in 120 patients.

Symptomatic staghorn renal calculi were removed from 106 of 124 kidneys (85%) with percutaneous ultrasonic lithotripsy. All remaining fragments were less than 5 mm in greatest diameter, small enough to pass spontaneously. Use of two or more access routes was necessary in 91 kidneys (73%), and 29 patients (24%) required multistage nephrolithotripsy for complete stone removal. The total operative time averaged 162 minutes per patient. The average hospitalization period was 12.5 days, and the average convalescence time after discharge was 15 days. The most common adverse effect was bleeding necessitating transfusion (57%). Infection occurred in 27% of patients and may be intrinsic to removal of these infected stones. There was one death in the study group: a patient with multiple medical problems died of myocardial infarction. Successful stone extraction requires a clear understanding of renal anatomic features, properly placed access routes, and radiologic-urologic expertise. It is concluded that staghorn calculi can be safely and effectively treated with the use of percutaneous techniques.

Adult