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Background: Cardiomyopathy (CM) remains one of the leading cardiac causes of death in children, although in the majority of cases, the cause is unknown. To have an impact on morbidity and mortality, attention must shift to etiology-specific treatments. The diagnostic evaluation of children with CM of genetic origin is complicated by the large number of rare genetic causes, the broad range of clinical presentations, and the array of specialized diagnostic tests and biochemical assays., Methods and Results: We present a multidisciplinary diagnostic approach to pediatric CM of genetic etiology. We specify criteria for abnormal left ventricular systolic performance and structure that suggest CM based on established normal echocardiographic measurements and list other indications to consider an evaluation for CM. We provide a differential diagnosis of genetic conditions associated with CM, classified as inborn errors of metabolism, malformation syndromes, neuromuscular diseases, and familial isolated CM disorders. A diagnostic strategy is offered that is based on the clinical presentation: biochemical abnormalities, encephalopathy, dysmorphic features or multiple malformations, neuromuscular disease, apparently isolated CM, and pathological specimen findings. Adjunctive treatment measures are recommended for severely ill patients in whom a metabolic cause of CM is suspected. A protocol is provided for the evaluation of moribund patients., Conclusions: In summary, we hope to assist pediatric cardiologists and other subspecialists in the evaluation of children with CM for a possible genetic cause using a presentation-based approach. This should increase the percentage of children with CM for whom a diagnosis can be established, with important implications for treatment, prognosis, and genetic counseling.

We performed bilateral femoral artery dissections in a single 50 kg mongrel dog. Digital fluoroscopic arteriograms documented the luminal diameter of the left iliac and right superficial femoral arteries. Balloon thrombectomy catheter passage was performed through hemostatic sheaths by 12 surgeons. Embolectomy balloons were filled with radiographic contrast material and the balloon catheter diameter was compared with the underlying vessel diameter. The percentage of overdistention of the embolectomy balloon relative to the arterial wall was 23% +/- 5% in the iliac artery and 40% +/- 13% in the femoral artery. Over a 25-month period, we used fluoroscopically assisted thromboembolectomy to treat 21 patients with acute arterial or graft occlusions. As the balloon was gently withdrawn to extract intravascular thrombus, deformities of the compliant balloon profile caused by underlying arterial lesions were identified fluoroscopically and their locations recorded to facilitate further treatment. After initial clot removal in these 21 patients, 15 residual lesions were documented. Repeat thrombectomy (n = 8), balloon angioplasty (n = 3), and placement of intravascular stents (n = 4) eliminated all 15 lesions. Luminal continuity was successfully restored in all 21 of these patients, 10 of whom required distal open vascular reconstruction to correct existing outflow artery disease. Fluoroscopically assisted thromboembolectomy is a simple and safe method for treating acute arterial or graft occlusions in patients with diffuse arteriosclerosis. It minimizes arterial damage and blood loss during balloon thrombectomy and reduces the need for intravascular contrast agents. It also has the potential to facilitate accurate identification, localization, and treatment of significant underlying arterial lesions.

Controversy exists over the value of intraoperative monitoring and shunting in patients undergoing carotid endarterectomy. Although it is widely believed that contralateral carotid occlusion and previous stroke mandate intraoperative shunting, the susceptibility of these two groups of patients to cerebral ischemia during carotid artery endarterectomy is not well defined. Somatosensory evoked potentials (SSEPs) were monitored in 113 carotid artery endarterectomy patients. Of these, 32 (28.3%) had a previous stroke, 24 (21.2%) had a contralateral carotid occlusion and 33 (29.2%) were diabetic. There were no deaths and only one perioperative stroke (0.9%). Cerebral ischemia occurred in 14 patients (12.4%). Six of these patients had a contralateral carotid occlusion. Some 29 patients (25.7%) were shunted, including 10 with contralateral carotid occlusions that did not have major SSEP changes. In the latter half of the study, 14 patients with contralateral carotid occlusions were selectively shunted (six shunted, eight not shunted) with no neurological complications. Thirty-two patients with prior strokes were selectively shunted (nine shunted, 23 not shunted); of these, one shunted patient undergoing combined carotid artery endarterectomy and coronary artery bypass grafting had a perioperative stroke. Intraoperative monitoring with SSEPs accurately identifies cerebral ischemia secondary to carotid clamping as well as patients requiring shunts. With use of intraoperative SSEP monitoring, selective shunting may be safely performed in patients with a contralateral carotid occlusion or a previous stroke.

Purpose: This study was undertaken to evaluate our results of polytetrafluoroethylene (PTFE) tibial and peroneal artery bypasses done for limb salvage., Methods: Within a group of patients undergoing infrainguinal limb salvage bypasses at our institution between January 1986 and May 1995, 63 patients faced an immediate amputation, had no autologous vein on duplex examination and operative exploration, and had only a tibial or peroneal artery as an outflow vessel for bypass. Most of these patients (82%) had two or more prior ipsilateral infrainguinal bypasses. These 63 patients underwent 66 PTFE bypasses to a tibial or peroneal artery without a distal anastomotic vein cuff or an adjunctive arteriovenous fistula. Our results were then compared with those reported from infrapopliteal (crural) bypasses performed with alternate autologous vein sources or PTFE in conjunction with various recommended adjuncts., Results: The 3- and 5-year cumulative primary graft patency rates for our PTFE infrapopliteal bypasses were 39%+/-7% and 28%+/-9%, respectively. Secondary graft patency rates were 55%+/-8% and 43%+/-10% at 3 and 5 years, respectively. Limb salvage rates were 71%+/-7% at 3 years and 66%+/-8% at 5 years. Two-year actuarial patient survival rate was only 67%+/-7%., Conclusions: These results indicate that a PTFE bypass to an infrapopliteal artery remains a worthwhile option in patients without usable autologous vein. The secondary patency and limb salvage rates were acceptable in this setting and were not significantly different from the best results reported with prosthetic tibial/peroneal bypasses with distal vein cuffs or patches (74% at 1 year; 58% at 3 years), arteriovenous fistulas (71% at 1 year) or composite arm vein grafts (39% and 29% at 3 and 5 years, respectively).

Purpose: The purpose of this report was to determine differences in presentation, bacteriology, management, and outcome of early (EGIs) versus late extracavitary arterial graft infections (LGIs)., Methods: Between July 1, 1979, and June 30, 1994, we treated 141 patients with infected extracavitary arterial grafts (112 prosthetic, 29 vein) with selective partial or complete graft preservation., Results: A total of 99 (70%) EGIs (< 2 months) and 42 (30%) LGIs (4 to 96 months) were involved. The hospital mortality rate was 14% (20 of 141), and the amputation rate in survivors was 13% (16 of 121). No significant difference in mortality (16% [16 of 99] vs 10% (4 of 42]) or limb loss (16% [13 of 83] vs 8% [3 of 38]) was seen between EGIs and LGIs, respectively (p > 0.05). Patients with EGIs were as likely to have a disrupted anastomosis (17% [17 of 99] vs 21% [9 of 42]) or systemic sepsis (4% [4 of 99] vs 4% [2 of 42]) as patients with LGIs, respectively (p > 0.05). Patients with EGIs were more likely to have patent, intact grafts and to be treated by complete graft preservation (61% [61 of 99] vs 26% [11 of 42]) (p = 0.0001). In comparison, patients with LGIs were more likely to have occluded grafts and to require subtotal graft excision (48% [20 of 42] vs 18% [18 of 99]) (p = 0.0001). Surviving patients with EGIs treated by complete graft preservation were more likely to have successful healing of their wounds after long-term follow-up (average 3 years) than patients with LGIs (79% [41 of 52] vs 40% [4 of 10], respectively) (p = 0.03). The pathogens cultured from wounds of EGIs versus LGIs were pure gram-positive bacteria in 49 (49%) versus 19 (46%), pure gram-negatives in 18 (18%) versus 11 (26%), and both types in 33 (33%) versus 12 (28%) (p > 0.05)., Conclusion: Complete graft preservation can be attempted more frequently and is more likely to be successful in EGIs than in LGIs. No difference in bacteriology was seen between the two groups. Graft-preserving treatment can be successful but should only be cautiously attempted in patients with late extracavitary arterial graft infections.

High levels of neurofilament (NF) mRNA expression are attained during early postnatal development and are a major determinant of axonal size. High level NF expression is also dependent upon axonal continuity since NF mRNA levels are down-regulated after nerve transection. This study shows that both postnatal up-regulation and axotomy-induced down-regulation are altered by deletion of 3'-UTR from the mouse light NF subunit (NF-L). Transgenes with (NF-L+) or without (NF-L-) 3'-UTR display similar patterns of neuron-specific expression but differ in their respective levels of expression. Whereas changes in the level of NF-L+ mRNA parallel those of the endogenous mouse NF-L mRNA, changes in the level of NF-L- mRNA differ from the pattern of endogenous NF-L expression during postnatal up-regulation and axotomy-induced down-regulation. Specifically, the NF-L- transgene undergoes a 3-fold aberrant up-regulation between embryonic days 15 (E15) and 18 (E18) and has lost its susceptibility to axotomy-induced down-regulation. Studies of transfected P19 cells show that 3'-UTR deletion leads to a severalfold stabilization of NF-L mRNA and an increase in steady-state mRNA level. The findings support the working hypothesis that the 3'-UTR contains determinants that alter stability and that stabilization of NF-L mRNA regulates the levels of NF-L mRNA in neuronal tissues and cells.

Purpose: To determine whether magnetic resonance (MR) arthrography of the elbow can demonstrate precisely an ulnar collateral ligament (UCL) abnormality in the throwing athlete., Materials and Methods: Forty college-level and professional throwing athletes (age range, 18-40 years) underwent saline-enhanced MR arthrography of their injured elbows. MR findings were compared with the surgical findings., Results: Saline-enhanced MR arthrography was positive in 24 of 26 individuals with UCL tear confirmed at the time of surgery. Eighteen (95%) of 19 complete UCL tears and six (86%) of seven partial UCL tears were diagnosed with MR arthrography. Two false-negative findings and no false-positive findings were obtained., Conclusion: Saline-enhanced MR arthrography of the elbow is a new application of a previously described technique used in the shoulder. It is useful for demonstration of subtle and gross UCL abnormalities in the throwing athlete.

Purpose: Occlusive disease of the aortoiliac segment may lead to limb-threatening ischemia, if coexisting disease is present in the femoral, popliteal, or tibial arteries. The combined treatment of severe aortoiliac and infrainguinal disease with standard techniques may be hazardous or contraindicated in patients with multiple previous reconstructions, severe comorbid medical illnesses, or both. This report summarizes the technical feasibility and early results of aortoiliac endovascular stented grafts (ESGs) in combination with conventional surgical reconstructions for the treatment of multilevel arterial occlusive disease., Methods: Seventeen patients with multilevel aortoiliofemoral limb-threatening occlusive disease had an ESG inserted to treat long-segment occlusive disease followed by a conventional surgical bypass. ESGs originated from the aortoiliac junction (seven) or the common iliac artery (10) and were inserted into the common femoral (nine), superficial femoral (four), or deep femoral (four) artery. ESG lengths ranged from 16 to 30 cm (mean, 21 cm). Conventional surgical bypasses were constructed from polytetrafluoroethylene (15) or saphenous vein (two) and extended to the popliteal (12), tibial (two), or contralateral femoral (three) arteries., Results: Technical success in graft insertion was achieved in 17 (94%) of 18 attempted ESG procedures. The 1-year primary and secondary cumulative patency rates for ESGs were 94% +/- 10% and 100%, respectively, whereas the 1- and 2-year patency rates for the extravascular grafts were 92% +/- 10% and 100%, respectively. Four patients had minor postprocedure complications (23%), and no deaths occurred. One patient lost his limb at 16 months because of severe pedal sepsis., Conclusions: Transluminally placed stented grafts in combination with conventional surgical infrainguinal bypasses are a technically feasible and potentially safe option for the treatment of limb-threatening aortoiliofemoral occlusive disease and have demonstrated encouraging early patency. Long-term follow-up will be necessary before widespread application of this technique is advocated.

A spherical acrylic phantom was designed for quality assurance measurements of dynamic radiosurgery. The phantom consists of two mating hemispheres mounted on a base plate. The interhemispheric plane may be oriented at any angle to the base, the angle being identified by visible marks on the base plate of the phantom. The phantom has a set of replaceable, radiologically identifiable markers, suitable for Computed Tomography (CT), Magnetic Resonance (MR), and Digital Subtraction Angiography (DSA) imaging. The frame coordinates of each marker are calculated from its known positions with respect to the center of the sphere. The measured errors of these positions using CT and MR images, were within the voxel size of the displayed image, while for DSA images the error was greater than 2.5 mm at the periphery of the image. The calculated depths from the planning software, for various beam intersection points to the isocenter, agreed within 0.6 mm with the known depths. A variation of 3.6 +/- 2.6 mm in the calculated depths was observed between using MR and CT image data. This difference results in a 1% variation in Tissue Maximum ratio (TMR) calculations. Comparisons of measured and known volumes resulted in differences of 8%-10%.

Background: Initial antibiotic treatment of extracavitary arterial graft infections is usually empiric or based on Gram's stain findings. Increasing virulence of bacteria causing extracavitary arterial graft infections may render previous choices of antibiotics obsolete. The purposes of this study were to correlate Gram's stain findings of gram-positive bacteria and gram-negative bacteria with wound cultures and provide a microbiologic basis for appropriate initial antibiotic therapy., Methods: Between July 1, 1979 and June 30, 1994, specimens obtained on the day of admission from purulent wounds involving 113 extracavitary arterial graft infections were retrospectively reviewed for Gram's stain and culture and sensitivity results., Results: Gram's stain findings correlated with final cultures on only 28 of 113 cases (25%), including 20 of 48 pure gram-positive, 2 of 24 pure gram-negative, and 6 of 41 mixed bacterial cultures. Staphylococcus aureus was the most common gram-positive bacteria cultured (43 isolates) and Pseudomonas species was the most common gram-negative bacteria (25 isolates). Bacteria were sensitive to a first-generation cephalosporin in only 32% (36 of 113) of infections. A combination of vancomycin and either ticarcillin-clavulanic acid or ceftazidime, which have minimal toxicity and provide excellent coverage against staphylococci, Pseudomonas, and other gram-negative bacteria, would have covered 96% (109) and 95% (107) of cultured organisms, respectively., Conclusions: Regardless of Gram's stain findings, current recommendations for initial treatment of extracavitary arterial graft infections should include vancomycin and ceftazidime or ticarcillin-clavulanic acid until final culture and sensitivity results dictate the use of more selective antibiotics.

Radiosurgery using the dynamic rotation technique with a single isocentre was introduced at the Toronto-Bayview Regional Cancer Centre (T-BRCC) in 1988. Since then, over 100 patients have been treated. It was soon recognized that 25-30% of patients were referred with either non-spherical lesions or multiple lesions located sufficiently close together that consideration had to be given to the overlapping dose distributions throughout the treated volume. To treat these more complex targets a multiple isocentre technique was developed which also took account of these effects and the resulting normalization problem. This technique was implemented in September 1992. Comparisons between calculated doses and actual doses delivered have been undertaken using a spherical phantom containing radiochromic film. Measured dose distributions agreed with the planned distributions to within +/- 1 mm. The effect of multiple isocentres on the penumbra of dose distributions has been examined. The methods adopted for the normalization of treatment plans and clinical examples illustrating the application of the multiple isocentre technique are presented.

Purpose: The purpose of this study was to perform a preliminary histopathologic analysis of explanted human endovascular stented grafts from patients treated for occlusive disease., Methods: Over a 16-month period, 26 endovascular stented grafts were placed in 21 patients with limb-threatening ischemia caused by aortoiliac or femoral artery occlusive disease. All grafts were inserted through open arteriotomies remote from the region of primary disease. During the follow-up period, two patients died of preexisting heart disease 2 weeks and 7 months after grafting, and a portion of their endovascular grafts were the surrounding artery was explanted. Specimens from five other endovascular grafts were obtained during surgical revision for graft stenosis after 3 and 6 weeks and for outflow artery stenosis after 3, 5, and 6 months. All specimens were formalin fixed and studied with hematoxylin and eosin and trichrome staining and immunohistochemically for factor VIII-related antigen, alpha actin smooth muscle, macrophage antigen (MAC-387) and PC-10 (a mouse monoclonal antibody which specifically recognizes proliferating cell nuclear antigen in paraffin sections)., Results: Three weeks after placement of the stented grafts, organizing thrombus was present on both surfaces of the expanded polytetrafluoroethylene (PTFE) grafts. At 6 weeks, evidence of a neointima with overlying endothelium was seen in the perianastomotic region, and 3 months after grafting it was seen 1 to 3 cm from the anastomosis. The specimen explanted at 5 months demonstrated factor VIII-positive cells 8 cm from the anastomosis. The histopathologic condition of the external capsule appeared to vary, depending on the presence or absence of an external wrap on the PTFE graft and on which layer in the arterial wall the graft was inserted. A foreign body reaction characterized by multinucleated giant cells was seen adjacent to wrapped grafts or around those placed in an intraadventitial plane. Grafts inserted within the media were surrounded by orderly, arranged, smooth muscle cells and few mononuclear cells. Extensive smooth muscle cell proliferation (PC-10 activity) was not seen within native artery atherosclerotic plaques peripherally displaced and external to prosthetic endovascular grafts., Conclusions: These preliminary observations on the healing of PTFE endovascular stented grafts in human beings demonstrate limited plaque hyperplasia and the presence of endothelial cells on the luminal surface remote from the graft-artery anastomosis. It is unclear whether this is a unique manifestation of healing in prosthetic grafts inserted within the walls of arteries.

Since July 1989, 66 patients have received stereotactic radiosurgery for arteriovenous malformations of the brain. All cases were reviewed by our multidisciplinary group. As result of our treatment algorithms these patients underwent stereotactic radiosurgery, either as the sole therapy or as part of combined modality treatment. Using a 6 MV linear accelerator, we have usually employed doses of either 15 or 20 Gy to the edge of the lesion, ensuring that critical normal structures do not receive a dose in excess of 15 Gy. Of the initial 24 patients followed for a minimum of 2 years, 12 have complete obliteration documented by angiography; 8 have > 90% obliteration (several have deferred further angiographic follow-up which may show progression to complete obliteration); 3 have had the nidus diminish; and one has had no change. Within this cohort, one patient experienced a transient acute effect; one patient has developed a minor late effect; one suffered a fatal hemorrhage despite ongoing response to radiosurgery; one has recently undergone retreatment.

In our centre, 111 patients have been treated with linear accelerator stereotactic radiosurgery. Angiographic, CT and MRI images are generated and the target coordinates calculated in 3 dimensions. For CT scanning, cross sections of perpendicular and oblique fiducial markers are seen. For follow-up CT scans done without the frame, a virtual frame is generated by means of a computer program that places fiducial markers on each CT scan cut, as if the patient had been wearing the OBT frame and the scan produced with the gantry parallel to the base of the frame. The position of the oblique marker may be calculated by knowing the thickness and position of each CT cut. Various natural fiducial markers (bony landmarks) are identified by coordinates in the scan with the patient wearing the real frame and in the scan with the virtual frame applied. A transformation matrix is utilized to establish the equivalence between the original CT scan with the real frame applied and subsequent scans without the real frame but with the virtual frame applied. In effect, the virtual frame is re-applied in exactly the same position as the real frame. Lesion measurements may then be duplicated and growth or regression accurately established. The uncertainty in this system of re-application resides in possible patient movement, CT scan slice thickness and inter-observer error in the identification of natural fiducial markers.

Endovascular grafting is a technique that combines the use of intravascular stents and prosthetic grafts to fabricate devices with unique properties. The purpose of this study is to describe the use of endovascular graft technology in the treatment of failed or failing standard aortoiliofemoral reconstructions. Over a 15-month period five patients with limb-threatening ischemia and failed aortofemoral or iliofemoral reconstructions underwent successful placement of six endovascular grafts to revascularize seven severely ischemic lower extremities. Standard thin-walled 6 mm polytetrafluoroethylene grafts and Palmaz balloon-expandable stents were used to fashion each reconstruction. In addition to the primary endovascular grafts, three patients underwent immediate femoropopliteal bypasses to improve distal outflow and one patient had a femorofemoral bypass graft to restore circulation to the contralateral ischemic extremity. The ankle/brachial indices of all patients significantly improved after the procedure (from a mean of 0.32 to a mean of 0.75) and all grafts are patent to date (mean follow-up 10 months). There were no deaths or limb loss in this group of patients. These favorable results indicate that this minimally invasive approach, which permits a new arterial graft to be inserted through a remote access site, is a valuable method for providing unobstructed arterial inflow after aortoiliofemoral graft failure. This procedure may be particularly valuable when there are contraindications to the use of axillary arteries or the thoracic aorta as alternatives to complex reoperative abdominal aortic surgery.

Stem cells isolated from the ventricular zone of embryonic day 12.5 rat telencephalon progressively proliferate and differentiate in vitro into three major classes of amino acid-containing neurons, glutamate, aspartate, and GABA. We quantitatively examined the effect of basic fibroblast growth factor (bFGF) and nerve growth factor (NGF) on amino acid-containing neurons. bFGF caused a threefold increase in glutamate-containing neurons, while the number of GABA- and aspartate-containing neurons was not significantly changed. In contrast, NGF did not alter the number of amino acid-containing neurons. The ratio of glutamate- to GABA-containing neurons in untreated or NGF-treated cultures was 0.6:1. In the bFGF-treated cultures, this ratio was 1.4:1, which closely approximates the ratio in the cerebral cortex in vivo. Treatment with antisense oligonucleotides targeted to bFGF mRNA provoked a 50% decrease in the number of glutamate-containing neurons but had no significant effect on the GABA-containing neurons. Thus, diffusible factors such as bFGF may play an important role in determining the relative proportion of excitatory versus inhibitory neurons in the cerebral cortex by selectively regulating the proliferation of stem cells committed to different neurotransmitter phenotypes.

Neurofilament (NF) mRNAs in primary sensory neurons are long-lived transcripts that undergo transcription-dependent destabilization when placed in primary culture [32]. Destabilization of NF transcripts implies that the transcripts are stabilized in high-expressing neurons and that stabilization may coordinate and increase levels of NF expression. The present study examines the stabilities of the three NF subunit mRNAs in postnatal cultures of dorsal root ganglia (DRG) to determine whether increased stability of NF mRNAs could be responsible for the coordinate postnatal upregulation of the three NF subunits [29]. The studies show that the light (NF-L), mid-sized (NF-M) and heavy (NF-H) NF mRNAs are lost at 8 and 16 h in primary cultures from postnatal day 2 (P2) rats, but much less so in cultures from postnatal day 16 (P16) and day 30 (P30) rats. Losses of each NF mRNAs in P2 cultures occurs simultaneously in the presence or absence of actinomycin. The findings support the view that stabilization of NF transcripts contribute to the high and coordinate level NF expression and that components of the stabilizing process are acquired during postnatal development.

In our centre, 111 patients have been treated with linear accelerator stereotactic radiosurgery. Angiographic, CT and MRI images are generated and the target coordinates calculated in 3 dimensions. For CT scanning, cross sections of perpendicular and oblique fiducial markers are seen. For follow-up CT scans done without the frame, a virtual frame is generated by means of a computer program that places fiducial markers on each CT scan cut, as if the patient had been wearing the OBT frame and the scan produced with the gantry parallel to the base of the frame. The position of the oblique marker may be calculated by knowing the thickness and position of each CT cut. Various natural fiducial markers (bony landmarks) are identified by coordinates in the scan with the patient wearing the real frame and in the scan with the virtual frame applied. A transformation matrix is utilized to establish the equivalence between the original CT scan with the real frame applied and subsequent scans without the real frame but with the virtual frame applied. In effect, the virtual frame is re-applied in exactly the same position as the real frame. Lesion measurements may then be duplicated and growth or regression accurately established. The uncertainty in this system of re-application residues in possible patient movement, CT scan slice thickness and inter-observer error in the identification of natural fiducial markers.

Objective: The authors report on their 20-year experience with 120 patients with infected extracavitary prosthetic arterial grafts (95 polytetraflouroethylene, 25 Dacron). Throughout this experience, an effort was made, when appropriate, to salvage all or a portion of these infected grafts., Methods: When patients had arterial bleeding (20 cases) or systemic sepsis (6 cases), immediate graft excision was performed. When the infected graft was occluded (43 cases), subtotal graft excision was performed, leaving an oversewn 2- to 3-mm graft remnant to maintain patency of the artery. Complete graft preservation was attempted in 51 cases in which the graft was patent, the patient was not septic, and the anastomoses were intact. Aggressive operative wound debridement was repeated, as necessary, to achieve wound healing. The preferred method of revascularization, when necessary, included secondary bypasses tunneled through uninfected (often lateral) routes. Follow-up averaged 3 years (range, 1 month-20 years)., Results: This strategy resulted in a hospital mortality of 12% (14/120) and a hospital amputation rate in survivors of 13% (14/106 threatened limbs). Of the surviving patients treated by complete graft preservation, the hospital amputation rate was only 4% (2/45) and long-term complete graft preservation was successful in 71% (32/45) of cases. Partial graft preservation also proved successful in 85% (35/41) of surviving patients who had occluded grafts. Successful complete graft preservation was as likely when gram-negative or gram-positive bacteria were cultured from the wound, with the exception of Pseudomonas (successful graft preservation in only 40% [4/10] of cases)., Conclusion: Based on this 20-year experience, the authors conclude that selective partial or complete graft preservation represents a simpler and better method of managing infected extracavitary prosthetic grafts than routine total graft excision.

Purpose: Intravascular stents have become important tools for the management of vascular lesions; however, stents in combination with vascular grafts have only recently reached clinical application. This report describes an experience with stented grafts for the treatment of penetrating arterial trauma., Methods: Seven transluminally placed stented grafts were used to treat one arteriovenous fistula and six pseudoaneurysms. These grafts were successfully inserted percutaneously or through open arteriotomies that were remote from the site of vascular trauma. The devices were composed of balloon-expandable stainless steel stents covered with polytetrafluoroethylene grafts., Results: Patency up to 14 months was achieved (mean follow-up 6.5 months) with these stented grafts. The use of stented grafts appears to be associated with decreased blood loss, a less invasive insertion procedure, reduced requirements for anesthesia, and a limited need for an extensive dissection in the traumatized field. These advantages are particularly important in patients with central arteriovenous fistulas or false aneurysms who are critically ill from other coexisting injuries or medical comorbidities., Conclusions: The use of stented grafts already appears justified to treat traumatic arterial lesions in critically ill patients. Although the early results with the seven cases in this report are encouraging, documentation of long-term effectiveness must be obtained before these devices can be recommended for widespread or generalized use in the treatment of major arterial injuries.

Background: Endovascular stented grafts employ a new technique that blends intravascular stent and prosthetic graft technologies. These devices may be used to treat arterial aneurysms, occlusive disease, and vascular injuries. This report describes the application of stented grafts to the treatment of limb-threatening ischemia secondary to occlusive disease of the aorta, iliac, and femoral arteries., Methods: Three patients with limb-threatening ischemia and severe comorbid medical illnesses were treated with transvascular stented grafts that were composed of 6-mm thin-walled polytetrafluoroethylene grafts and Palmaz balloon expandable stents. The grafts were inserted through a cutdown in an artery remote from the site of occlusion and introduced into the vascular system within 14-Fr introducer sheaths., Results: Technical success was documented in all three patients with restoration of arterial continuity following stent graft deployment. Patency and limb salvage has been achieved to 1 year. One patient required further dilatation of the proximal stent at 6 weeks. Complications were limited to an iliofemoral deep vein thrombosis in one patient., Conclusions: Endovascular stented grafts can be inserted to treat limb-threatening ischemia. Although these initial results are encouraging, greater experience in more patients observed for longer periods of time is necessary before this technique can be advocated for widespread use.

We have investigated the DNA elements responsible for transcription from the proximal portion of the mouse neurofilament heavy gene (NF-H) promoter by in vitro transcription using extracts from expressing (brain) and non-expressing (liver) tissues. We have found that constructs containing 5' region from -1314 to -115 exhibit a 3-5-fold higher level of NF-H promoter activity, relative to the adenovirus major late promoter (pML), in brain versus liver extracts. Deletion to -85 lowers the level of brain transcription by 2-fold, while deletion from -65 through -31 reduces transcription by 5-fold to a relatively strong (10% of pML) basal level. Basal level expression is observed in all deletions transcribed with liver extract. Deletion to -24 (TATA-less) abolishes promoter activity with both extracts. Deletion of the -115 to -65 region from a larger construct reduces transcription in brain extracts to basal levels, suggesting that this region contains the elements necessary for the brain-specific enhancement of promoter function. Mutation of a palindromic sequence within this region abolishes brain-specific enhanced promoter activity. This loss of enhanced transcriptional activity is correlated with the loss of a shifted band in gel shift assays. Our studies suggest that the sequence (-106)GGGGAGGAGG-(15 bp)-CCTCCTCCCC(-72) (where bp = base pairs) is important in brain-specific enhancement of transcription from the mouse NF-H promoter.

Radiosurgery has been advocated as a salvage treatment for relapsed patients with brain metastases. This report describes a phase I/II study of salvage radiosurgery for patients previously treated with whole brain irradiation. The study was opened in March 1989 and the last patient was treated in July 1992. All patients have been followed to recurrence at the radiosurgically treated site or to death. Twenty progressing metastases in 12 patients were treated using 14 radiosurgical procedures. The radiation dose was always 25 Gy with the 90% isodose volume encompassing all enhancing tumour. Nineteen metastases were evaluable at +4 weeks. There were no instances of progressive disease; there were three complete responses, six partial responses, and 10 metastases remained unchanged. Median survival from the date of radiosurgery was 6 months. Nine of 12 patients eventually failed at the radiosurgically treated site (two remain alive). Radiosurgery at the time of relapse provides temporary control of recurrent brain metastases with acceptable toxicity.

Hypocholesterolemic drug therapy has become a major focus of cardiovascular medicine because recent evidence has demonstrated that optimization of serum lipid levels results in decreased atherosclerotic cardiovascular risk. Niacin, a B-complex vitamin, is capable of lowering total serum cholesterol and triglyceride levels while simultaneously raising serum high-density lipoprotein cholesterol levels. However, the use of niacin can be complicated by the development of hepatotoxicity, hyperuricemia, and modest hyperglycemia. A patient is described who had an excellent lipid response to niacin therapy but developed the previously undescribed complication of severe, life-threatening hyperglycemia. Therefore, despite its low cost and demonstrated efficacy, because of potential very toxic side effects, niacin therapy needs to be carefully monitored.

A 29-year-old woman experienced overwhelming rubeola pneumonia requiring endotracheal intubation and mechanical ventilation. Treatment with high-dose corticosteroids and vitamin A was accompanied by a prompt clinical response. Further investigation of this novel therapy is needed.

The light (NF-L), mid-sized (NF-M) and heavy (NF-H) neurofilament (NF) genes were probed with methylation-sensitive restriction enzymes and patterns of methylation and expression of the NF genes were compared in tissues and cell lines of the mouse. The 5' regions of all three NF genes are identified as CpG islands that remain unmethylated in expressing and non-expressing tissues, although partial methylation occurs at -795 in NF-H and at -525 in NF-M. Methylation of the NF CpG islands is associated with the inactivation of NF genes in L cells and with the selective inactivation of NF-L and NF-M in Neuro 2a cells. We also show that methylation diminishes the ability of the NF promoters to drive transcription of a CAT reporter gene. Hence, the presence of CpG islands may be important in determining patterns of NF transcription in vitro. Moreover, the preservation of CpG islands may be an evolutionary link that bears upon the nature of the NF genes and the mechanisms that have evolved to limit NF expression.

The ultrastructural organization of association nuclei in the primate thalamus is largely unexplored. In the present study we have combined electron microscopy with immunocytochemistry for the acetylcholine synthesizing enzyme choline acetyltransferase (ChAT) to assess the cholinergic synaptic organization of the mediodorsal (MD) nucleus in macaque monkeys. The cholinergic innervation of the MD nucleus showed striking regional variations with the greatest density of immunoreactive axons and varicosities found within the parvicellular division. Electron microscopic examination revealed that these ChAT immunoreactive (ChAT-IR) axons were primarily small and unmyelinated. The majority of immunoreactive synaptic profiles were found within the extraglomerular neuropil (80.5%), with the remainder present in glomerular regions. Within the glomerular and extra-glomerular neuropil ChAT-IR profiles made contact with both conventional, presumably relay cell dendrites (CD), as well as with synaptic vesicle containing dendrites (SVCD) of local circuit neurons. In the glomeruli the frequency of synapses was approximately equal for CDs and SVCDs while in the extraglomerular areas 75% of the synaptic contacts were with CDs. ChAT-IR synaptic profiles had a diversity of junctional complex morphologies. Within glomeruli they made symmetric synapses with CDs and predominantly asymmetric with SVCDs. The majority of extraglomerular contacts (60%) were classified as asymmetric and these as well as the smaller number of symmetric synapses contacted both CDs and SVCDs. In accord with results of physiological studies, these anatomical data indicate that cholinergic input to thalamic nuclei influences relay cell activity both directly and indirectly via local circuit 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.

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)

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)

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.

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.

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.

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.

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.

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.

Light and electron microscopic immunohistochemistry was used to examine the time of emergence and distribution of GABA-containing cells in an association (prefrontal) and primary sensory (visual) region of the telencephalon at progressive fetal and postnatal stages of cortical maturation in the rhesus monkey. Thirty fetuses and six postnatal monkeys were examined beginning at embryonic day 41 (E41), the start of cortical neurogenesis, to birth (E165) and proceeding to maturity (greater than 5 years of age). The emergence and major developmental modifications in the distribution of immunoreactive neurons in both areas examined were nearly identical. GABA-immunolabeled neurons were present throughout the full thickness of the cerebral wall, including the cortical plate and the developmentally transient marginal, subplate, and ventricular zones, as early as E41. An important and surprising result was that a subset of bipolar migrating neurons in the subplate zone also contained GABA at these early stages. GABA-containing neurons in the ventricular and subventricular zones disappeared after E100, when neurogenesis is completed. In contrast, the number of immunoreactive multipolar and bipolar neurons within the subplate zone diminished between E100 and E131. By the first postnatal week, the distribution and density of GABA-containing neurons in the cortex appeared qualitatively similar to that observed in mature monkeys. The early appearance of GABA in cortical neurons and its expression by a population of migrating neurons suggest that a subset of cortical neurons may be committed to a transmitter phenotype independent of synaptic interactions and prior to attaining their adult positions in the maturing cerebral cortex.

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.

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.

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.

A patient with a neurenteric cyst located dorsal to the cervical spine and associated with occult cervical spinal dysraphism is described. The embryological theories that might explain the occurrence of such a lesion are discussed.

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.

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.

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.

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.

As delay in diagnosing unstable cervical spine injuries unnecessarily exposes patients to risk of neurologic injury, it is often recommended that complex radiologic investigations be performed on alert patients with neck pain, tenderness, or neurologic deficit despite normal plain radiographs. The optimal investigation of patients unable to reliably provide such information is less clear. How many X-rays are enough to clear the cervical spine? In order to answer this question, a retrospective review of 775 motor vehicle crash (MVC) victims was conducted. Ninety-two (12%) sustained cervical spine injury. Sixteen of these injuries were missed initially and, in a further 18 cases, the lateral cervical spine X-ray was wrongly interpreted as positive. Fifty-five per cent of patients with cervical injury had a Glasgow Coma Score (GCS) of less than 15 on admission. Lateral radiographic visualization of the complete cervical spine (including a swimmer's view as required) had a sensitivity of 83% and a specificity of 97%. The addition of open mouth (OM) and anteroposterior (AP) views detected all patients with unstable fractures except one man with a head injury who was unable to provide clinical clues to the diagnosis, but who suffered no additional harm as a result. A single lateral X-ray of the cervical spine is inadequate to exclude cervical spine injury in severely traumatized patients and the addition of OM and AP views still failed to identify unstable fractures in one of 385 patients in this series of MVC victims with GCS less than 15.(ABSTRACT TRUNCATED AT 250 WORDS)