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Biomedical subjects

M L Schwartz

Publications and source records attributed to M L Schwartz.

At least 19 recordsLinked to original sources
PubMed1992

Actinomycin prevents the destabilization of neurofilament mRNA in primary sensory neurons.

The levels of light, mid-sized, and heavy neurofilament (NF) mRNAs were compared to that of beta-actin mRNA in primary dissociated cultures of adult rat dorsal root ganglia (DRG). Decreases in the levels of all three NF mRNAs occur after 24 h in culture, mimicking the down-regulation of NF mRNAs in axotomized DRG neurons. The loss of NF mRNAs in DRG cultures is prevented by actinomycin and, to a lesser extent, by cycloheximide. Based on decay curves in actinomycin-treated cultures, the half-lives of NF mRNAs are at least 4 days in DRG neurons, but < 24 h in PC12 cells. Our data support the view that NF mRNAs are stabilized in DRG neurons and that stabilization prevents destabilization by a transcription-dependent process. We further propose that putative stabilizing factor(s) are able to prevent degradation of NF transcripts in intact neurons, but not in axotomized or cultured neurons.

Amanitins↗
PubMed1992

The safety of awake tracheal intubation in cervical spine injury.

As a referral centre for cervical spine injuries, we have routinely performed awake tracheal intubation when intubation was indicated. A retrospective case control study was undertaken to review the frequency of neurological deterioration and aspiration associated with our approach. Neurological deterioration was assessed by a change in level of injury or neurological grade at admission and discharge. Four hundred and fifty-four patients with critical cervical spine and/or cord injuries were reviewed over an eight-year period. A case group of 165 patients underwent tracheal intubation awake within two months of injury. A control group of 289 remained unintubated during the same period. A comparison of spinal neurological status between admission and discharge revealed no statistically significant difference in neurological deterioration between the two groups. This occurred despite a greater injury severity score in the case group. No evidence of aspiration during intubation was documented. We conclude that awake tracheal intubation is a safe method of airway management in patients with cervical spine injuries.

Adult↗
PubMed1992

Negative regulatory regions are present upstream in the three mouse neurofilament genes.

We have cloned and examined the 5' flanking regions of the heavy (NF-H), light (NF-L) and mid-sized (NF-M) mouse neurofilament (NF) genes in order to begin to characterize the regions of each gene that regulate NF transcription. Chimeric plasmids bearing the CAT reporter gene and deletion mutants of the upstream NF genes were transiently transfected into neuronal (PC12 and Neuro 2A) and non-neuronal (HeLa) cell lines. Constructs bearing upstream regions to -4000 in NF-H, to -5600 in NF-L and to -4500 in NF-M were expressed at low levels in neuronal and in non-neuronal cells. Progressive deletion of 5' flanking sequence to -385 in NF-H, to -325 in NF-L and to -505 in NF-M caused a several-fold increase of transcription from the transfected plasmids. Increases of transcription by deletion mutants followed a similar pattern in neuronal and in non-neuronal cell lines. Negative upstream regions are located between -1314 and -385 in NF-H, between -936 and -325 in NF-L and between -874 and -505 in NF-M. Additional negative regions are present further upstream in NF-L and in NF-H. The negative regions of NF-H and of NF-L suppress transcription when placed in either orientation in front of the SV40 or a heterologous NF promoter. These studies demonstrate that the three mouse NF genes possess similar functional features, namely, that of a relatively strong and promiscuous promoter with negative upstream elements. The role of the negative elements in regulating NF expression remains unclear.

Animals↗
PubMed1992

Management of infected lower extremity autologous vein grafts by selective graft preservation.

Between 1975 and 1991, we treated 16 patients with infected lower extremity autologous vein grafts performed for limb salvage by complete graft preservation. Traditional treatment of these infections includes immediate graft excision and complex revascularization procedures to prevent limb loss. The infection involved an intact anastomosis in 12 patients or the body of a patent graft in 4 patients. None of the patients was systemically septic. All patients were treated with appropriate intravenous antibiotics. Six patients were treated by placement of autologous tissue on the exposed graft (4 rotational muscle flaps, 2 skin grafts), and 10 were treated with antibiotic-soaked dressing changes and repeated operative débridements to achieve delayed secondary wound healing. This treatment resulted in a 19% (3 of 16) mortality rate and an 8% (1 of 13) amputation rate in survivors. Of the six patients managed by autologous tissue placement onto the infected graft, five patients had wounds that healed without complications, and one died of a myocardial infarction. Of the 10 patients treated by delayed secondary wound healing, 2 developed anastomotic hemorrhage, which resulted in death in 1 patient and above-knee amputation in the other, 1 died of a myocardial infarction, 1 developed graft thrombosis, and 6 had wounds that healed. Placement of autologous tissue to cover an exposed, infected patent vein graft with intact anastomoses may prevent graft dessication, disruption, and thrombosis, which renders graft preservation an easier, safer method of treatment compared with routine graft excision.

Aged↗
PubMed1992

Are gram-negative bacteria a contraindication to selective preservation of infected prosthetic arterial grafts?

Management of infected prosthetic arterial grafts has traditionally included total graft excision especially when gram-negative bacteria were cultured. Between 1973 and 1991 we treated 42 patients with infected prosthetic grafts (33 polytetrafluoroethylene (PTFE), 9 Dacron) by complete graft preservation when the graft was patent, the anastomoses were intact, and the patient did not have sepsis. The infection involved the anastomosis (36 cases) or the body (6 cases) of 33 peripheral grafts and the distal segment of five aortofemoral and four iliac-distal grafts. Cultures of the 42 infected grafts grew gram-positive bacteria in 33 cases and gram-negative bacteria in 22 cases. Treatment adjuncts included repeated, radical operative wound debridement and rarely (7 of 42) rotational muscle flaps. This management resulted in a 10% (4 of 42) hospital mortality rate and an amputation rate in survivors of 3% (1 of 38 threatened limbs). All four deaths were due to sepsis: gram-positive bacteria were cultured in all cases and gram-negative bacteria in two cases. Of the 38 survivors, 29 (76%) wounds healed and remained healed after average follow-up of 3 years (range, 1 to 18 years). Nine other patients required total graft excision for nonhealing wounds (7 cases) or delayed anastomotic hemorrhage (2 cases). Gram-negative bacteria were cultured in four, and gram-positive bacteria were cultured in six of these nine wounds. Four of nine (44%) graft infections that cultured Pseudomonas organisms healed without complications versus 23 of 33 (70%) wounds that cultured gram-positive bacteria, and 12 of 13 (92%) wounds that cultured gram-negative bacteria other than Pseudomonas organisms.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Vessel Prosthesis↗
PubMed1992

Natural history, duplex characteristics, and histopathologic correlation of arterial injuries in a canine model.

The treatment of patients with penetrating extremity trauma in proximity to major arteries as well as the nonoperative treatment of clinically occult arterial injuries remain controversial. Duplex ultrasonography (DUS) has recently been advocated in this setting. We therefore studied experimentally induced arterial injuries in dogs to correlate the natural history, duplex findings, and histopathologic condition of different injuries and to help define criteria for operation. Fifty-two canine femoral and carotid arteries were randomized to have surgically created intimal flaps (n = 15), crush injuries (n = 15), or lacerations (n = 15) or to be controls (n = 7). An experienced sonographer, blinded to the presence or type of injury, evaluated the vessels every 10 days for 1 month. Histopathologic study was performed 1 month after injury when the arteries were retrieved. The sensitivity (96.5%), specificity (86.4%), and accuracy (95.1%) of DUS in evaluating arterial injuries at 1 month correlated well with histopathologic evaluation. All arteries subjected to crush injuries showed abnormal duplex findings. These findings correlated well with the histologic picture of severe injury (arterial wall thickness = 2.72 x +/- 0.23 x control; intramural hemorrhage, 93%; mural thrombus, 60%). DUS and histologic study revealed healing of intimal flaps in 27% of the arteries. Other intimal flaps deteriorated (stenoses, 47%; dilation, 13%; occlusion, 13%). Most lacerations (86%) revealed duplex evidence of healing within 10 days of injury. This was confirmed by histologic study at 1 month in 73% of lacerated arteries. This study confirms the accuracy of DUS in diagnosing various arterial injuries and shows that the natural history of these injuries varies with the mechanism of injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Injury severity score, head injury, and patient wait days: contributions to extended trauma patient length of stay.

The ability of level I trauma units to operate efficiently may be hampered by the presence of a number of patients with an excessive length of stay (LOS). In an attempt to determine causes for and suggest potential solutions to the long-term occupation of beds in an acute care trauma facility, the cases of patients with extended LOSs in a level I trauma unit were examined. Study patients were survivors admitted between January 1, 1986, and December 31, 1989. Patients with a LOS greater than one standard deviation above the mean (n = 221) were assigned to the Long LOS group, and the remaining 1250 patients to the Short LOS group. Long and Short LOS patient groups were compared on a number of variables including injury Severity Score, number of body systems injured, surgical procedures required, blood products used, AIS scores per body region, and patient wait days. Both an increased severity of injury and a lack of available chronic and rehabilitation beds for the head-injured patients contributed to excessive patient LOS in this acute care setting. Additional rehabilitation and chronic care beds are required to free acute care beds for the efficient operation of a level I trauma unit.

Craniocerebral Trauma↗
PubMed1992

Neurophysiologic diagnosis in uncooperative trauma patients: confounding factors.

Median, ulnar, and posterior tibial nerve somatosensory evoked potential (SSEP) studies were performed on a total of 239 comatose or uncooperative trauma patients with head injuries. Twenty-six of those patients were suspected of having an additional spinal cord injury. One patient had more than one suspected spinal cord injury and two patients had a suspected spinal cord injury and a suspected peripheral nerve injury. Eleven of the suspected spinal cord injuries were confirmed and 13 were not confirmed by the SSEP studies. In three patients the SSEP study proved inadequate to add further information on the suspected spinal cord injury. Sixteen patients with suspected spinal cord injuries were able to cooperate with a neurologic examination approximately 6 months after injury and the SSEP findings were clinically verified in all 16 patients. Eleven patients were suspected of having an additional peripheral nerve injury. Four injuries were confirmed and seven not confirmed by the SSEP studies. Eight of those patients were able to cooperate with the follow-up neurologic examination, and the SSEP findings were clinically verified in all eight. Two patients suspected of having an additional spinal cord injury had unsuspected peripheral nerve injuries discovered by the SSEP studies. One patient was cooperative at follow-up and the SSEP findings were clinically verified. In our experience, SSEP studies have been an important diagnostic tool in the study of uncooperative trauma patients.

Adolescent↗
PubMed1992

Unsuspected preexisting saphenous vein disease: an unrecognized cause of vein bypass failure.

Our prior anecdotal experience with unsuspected preexisting saphenous vein disease prompted us to study its incidence, its relation to graft failure, and to identify techniques for its detection. Thick-walled, postphlebitic sclerotic occluded, postphlebitic sclerotic recanalized, calcified, and varicose vein lesions were detected in 63 (12%) of 513 infrainguinal vein bypasses. In 13 (2% to 5%) cases, severe saphenous vein disease precluded use of the vein. In the remaining 50 cases, the entire vein or a portion thereof, with minimal or unsuspected disease, was used for bypass. Early graft failures occurred in 10 (20%) of the 50 cases. The cumulative primary patency rate at 30 months for bypasses performed with diseased veins was 32%. This was significantly less than the 73% cumulative primary patency rate for bypasses with veins without detectable disease (p less than or equal to 0.001). Retrospective evaluation of preoperative duplex ultrasonography (n = 21) originally used to evaluate saphenous vein length and diameter correctly identified thick-walled, occluded, calcified, and varicose veins in 62% of cases. Intraoperative methods of vein evaluation included inspection, palpation, irrigation, catheter or valvulotome insertion to identify obstruction, and intraoperative arteriography. Histologic examination of diseased veins demonstrated a spectrum of disease with thickening of the intima and media, vein wall calcification, and luminal recanalization. We conclude that (1) unsuspected preexisting saphenous vein disease occurs in approximately 12% of cases and results in both early and late graft failures; (2) detection, in some cases, is possible with duplex ultrasonography and intraoperative techniques; and (3) diseased veins that are recanalized, calcified, or thick-walled should not be used if an alternative vein is available.

Chi-Square Distribution↗
PubMed1991

Dual mode of corticothalamic synaptic termination in the mediodorsal nucleus of the rhesus monkey.

Electron microscopic autoradiography (EM-ARG) was used to assess the synaptic organization of corticothalamic terminals in the parvicellular division of the mediodorsal thalamic nucleus. Examination of the synaptic organization in unreacted tissue revealed several distinct synaptic types distributed among glomerular and nonglomerular regions of the neuropil. Within glomeruli, three presynaptic terminal classes were found. The majority of profiles (as many as eight to ten per glomerulus) were presynaptic dendrites (PSDs) forming symmetric synaptic contacts with a central dendrite, and occasionally with other PSDs. One or two large terminals densely packed with round vesicles (LR terminals) were also present in each glomerulus. This terminal class made multiple asymmetric contacts with the central dendrite, as well as with many PSDs within the glomerulus. Finally, small terminals with round vesicles (SR terminals) formed asymmetric synaptic junctions with PSDs in some glomeruli. PSDs and SR terminals were also found in the extraglomerular neuropil, although in different proportions than in the glomeruli. In the extraglomerular neuropil SR terminals were the most abundant terminal class and these terminals made synaptic contacts with dendrites of all sizes. PSDs were seen in considerably smaller numbers than in the glomeruli. Finally, the extraglomerular neuropil contained a moderate number of small to medium terminals that formed symmetric synaptic junctions (SF terminals) with cell bodies and dendrites of all sizes. Synaptic profiles related to corticothalamic inputs were identified by injecting the prefrontal cortex of two rhesus monkeys with 3H-leucine and -proline and analyzing the distribution and morphology of radiolabeled terminals. Quantitative analysis of the density of silver grains over different tissue compartments revealed a positive labeling index for two terminal classes: SR and LR terminals. Labeled SR terminals were concentrated in the extraglomerular neuropil and labeled LR terminals were found within glomeruli where they formed synaptic contact with the central dendrite, as well as with presynaptic dendrites of the glomerulus. In contrast to many other thalamic nuclei, cortical input to the mediodorsal nucleus arrives via two distinctive synaptic pathways, one terminating extraglomerularly and the other terminating within the synaptic glomeruli. The dual mode of corticothalamic terminations in the mediodorsal nucleus suggests a more potent and possibly different role for cortical input in the regulation of neuronal activity in this association nucleus than in sensory nuclei of the thalamus.

Animals↗
PubMed1991

Prenatal specification of callosal connections in rhesus monkey.

Anatomical tracing and quantitative techniques were used to examine the tempo and pattern of maturation for callosal projection neurons in the monkey prefrontal cortex (PFC) during fetal and postnatal development. Nineteen monkeys were injected with retrograde tracers (fluorescent dyes, horseradish peroxidase conjugated to wheat germ agglutinin [WGA-HRP] or HRP crystals) at various ages between embryonic day 82 (E82) and adulthood. The size of injection sites was varied in fetal, newborn, and adult cases. In adults, labeled neurons were found in greatest density in the homotopic cortex of the opposite hemisphere and considerable numbers were also observed in a constellation of heterotopic areas including the medial and lateral orbital cortex, the dorsomedial convexity, and the pregenual cortex. The majority of labeled neurons were consistently concentrated in the lower half of layer III in all areas. In cases with large injection sites, callosal neurons of layer III formed a continuous and uninterrupted band that extended over the entire lateral surface of the prefrontal cortex spanning both homotopic and heterotopic areas. In contrast, in cases with small injection sites, the labeling of layer III neurons exhibited discontinuities. Between embryonic ages E82 and E89, injections limited to the cortical layers labeled only a small number of neurons in the opposite hemisphere, indicating that few callosal axons have invaded the cortex by this age. However, by E111 comparable injections labeled a large number of callosal neurons and many features of their distribution were adult-like. The number and constellation of cytoarchitectonic areas that were labeled in the frontal cortex of the opposite hemisphere were the same as in adults and the majority of callosal neurons were found in supragranular layer III. Finally, in fetal animals beyond E111, labeled neurons extended as a nearly unbroken band over a wide expanse of the dorsolateral PFC, resembling the pattern seen in adult monkeys with large injections. The conclusion we draw from these results, together with our earlier findings (Schwartz and Goldman-Rakic: Nature 299:154, 1982), is that callosal neurons whose axons enter the cortical layers of the primate prefrontal cortex achieve their mature laminar and areal distribution prior to birth and do so largely by cumulative processes.

Aging↗
PubMed1991

Early phenotype expression of cortical neurons: evidence that a subclass of migrating neurons have callosal axons.

The use of [3H]thymidine labeling in combination with various axonal transport tracers has revealed that a subset of migrating neurons in the fetal monkey cerebrum issue axons to the opposite cerebral hemisphere while still migrating to their final positions in the cortical plate. Other cortical neurons with the same "birthdate" (i.e., that underwent their last round of DNA synthesis on the same day) are not retrogradely labeled by tracer injections of the opposite hemisphere. These findings suggest that the cardinal distinction between projection and local circuit neurons may be specified in postmitotic neurons before they acquire their final positions in the cortex.

Animals↗
PubMed1991

Quality assurance for patients with head injuries admitted to a regional trauma unit.

The efficacy of trauma systems in reducing preventable deaths has been established but the methods of auditing care are still evolving. Various "audit filters" to identify which patients' charts should be reviewed have been proposed. An analysis of all patients admitted to the Regional Trauma Unit (RTU) over a 19-month period was conducted. Of 729 patients, 135 were identified as having suffered a traumatic intracranial hemorrhage (TICH). On review, neither delay in transfer from the emergency room to the operating room nor increasing time from the incident to the operating room correlated with increasing mortality. In contrast to delay, the Glasgow Coma Scale (GCS) score on admission correlated well with outcome. The charts of patients with anomalous outcomes based on admission GCS score were reviewed, and two possibly preventable deaths were identified. There were 48 patients with TICH who had no operations but there were no deaths attributable to a missed operation. There were 76 patients for whom the GCS score at the referring hospital and the GCS score on admission to the RTU were available. Seven of 19 patients who worsened on transfer declined because of significant pulmonary injuries. Anomalous outcomes based on admission GCS score and declining GCS scores are recommended as quality assurance filters.

Adult↗
PubMed1990

Searching for and predicting the activity of sites for DNA binding proteins: compilation and analysis of the binding sites for Escherichia coli integration host factor (IHF).

An analysis of the sequence information contained in a compilation of published binding sites for E. coli integration host factor (IHF) was performed. The sequences of twenty-seven IHF sites were aligned; the base occurrences at each position, the information content, and an extended consensus sequence were obtained for the IHF site. The base occurrences at each position of the IHF site were used with a program written for the Apple Macintosh computers in order to determine the similarity scores for published IHF sites. A linear correlation was found to exist between the logarithm of IHF binding and functional data (relative free energies) and similarity scores for two groups of IHF sites. The MacTargsearch program and its potential usefulness in searching for other sites and predicting their relative activities is discussed.

Bacterial Proteins↗
PubMed1990

Axonal dependency of the postnatal upregulation in neurofilament expression.

A coordinated up-regulation in the expression of all three neurofilament (NF) proteins occurs during postnatal development in the rat (Schlaepfer and Bruce, J Neurosci Res [in press], 1990a). In the present study, sciatic nerves were transected in neonatal rats in order to determine the effects of axotomy on the postnatal upregulation of NF expression in neurons of rat dorsal root ganglia (DRG). Left sciatic nerves were transected at postnatal day 3 (P3), 6 (P6), 8 (P8), or 10 (P10). mRNA and protein levels of the light (NF-L), mid-sized (NF-M), and heavy (NF-H) NF proteins were compared in L4 and L5 DRGs from the transected (left) vs. control (right) sides of the same animals at varying intervals after transection. When nerves were transected at P10, mRNA levels of all three NF proteins declined markedly in the parent DRG neurons, thereby completely interrupting the postnatal upregulation of NF expression. P10 transections also led to widespread chromatolytic changes in axotomized neurons, indistinguishable from those that occur in adult DRG following sciatic nerve transection (Goldstein et al., J Neurosci 7:1586-1594, 1987). Nerve transections at earlier (e.g., P3) neonatal timepoints also led to a decrease of NF expression, but to a lesser extent than that which resulted from a P10 transection. Also, P3 transections caused only minimal chromatolytic changes in the axotomized neurons. Thus, the postnatal upregulation of NF expression is dependent upon axonal continuity and the extent of axonal dependency increases during early postnatal development. These findings support the hypothesis that the postnatal upregulation of NF expression, the axotomy-induced downregulation of NF expression and the chromatolytic reaction to nerve transection are all dependent upon or responsive to axonal- or target cell-derived signals that are acquired during postnatal maturation.

Animals↗
PubMed1990

Median nerve somatosensory evoked potentials and the Glasgow Coma Scale as predictors of outcome in comatose patients with head injuries.

Median nerve somatosensory evoked potential (SSEP) grades and Glasgow Coma Scale (GSC) scores were obtained from 51 patients with head injuries within 1 week after the injury to determine the relationship of these scores, both individually and combined, to outcome scores obtained more than 6 months after the injury. SSEP grading was based on the presence or absence of the cortical evoked potential, the amplitude of the early cortically generated P22 wave form, and the conduction time through the brain (P/N13-N20 interpeak latency). SSEP responses from both sides of the brain were combined and graded from 1 to 6. The GCS was graded without the verbal component (maximum score, 10), because all patients were intubated. All patients were unresponsive to commands. Median SSEP grades correlated better with Glasgow Outcome Scale and Barthel Index scores (R = 0.57 and 0.64, respectively; P less than 0.00001) than GCS scores did (R = 0.35 and 0.37, respectively, P less than 0.00001), and combining SSEP grades and GCS scores did not improve the predictive power of the model (R = 0.57 and 0.64, respectively; P less than 0.00001). All SSEP Grade 1 patients (n = 13) either died or remained in a vegetative state. In contrast, all SSEP Grade 6 patients (n = 7) had a moderate disability or good recovery. This study demonstrates the prognostic value of early quantitative median nerve SSEP grading for patients with head injuries who are unresponsive to commands within 1 week after the injury.

Analysis of Variance↗