Accuracy of CT-Derived Patient-Specific Instrumentation for Total Ankle Arthroplasty: The Impact of the Severity of Preoperative Varus Ankle Deformity.

BACKGROUND: Significant preoperative varus tibiotalar deformity was once believed to be a contraindication for total ankle arthroplasty (TAA). Our primary goal was to evaluate the influence of increasing preoperative varus tibiotalar deformity on the accuracy of final implant positioning using computed tomography (CT)-derived patient-specific guides for TAA. METHODS: Thirty-two patients with varus ankle arthritis underwent TAA using CT-derived patient-specific guides. Patients were subcategorized into varying degrees of deformity based on preoperative tibiotalar angles (0°-5° neutral, 6°-10° mild, 11°-15° moderate, and >15° severe). Postoperative weightbearing radiographs were used to measure coronal plane alignment of the tibial implant relative to the target axis determined by the preoperative CT template. Average follow-up at the time of data collection was 36.8 months. RESULTS: Average preoperative varus deformity was 6.06° (range: 0.66°-16.3°). Postoperatively, 96.9% (30/31) of patients demonstrated neutral implant alignment. Average postoperative tibial implant deviation was 1.54° (range: 0.17°-5.7°). Average coronal deviation relative to the target axis was 1.61° for the neutral group, 1.78° for the mild group, 0.94° for the moderate group, and 1.41° for the severe group (P = .256). Preoperative plans predicted 100% of tibial and talar implant sizes correctly within 1 size of actual implant size. Conclusion. Our study supports the claim that neutral postoperative TAA alignment can be obtained using CT-derived patient-specific instrumentation (PSI). Furthermore, final implant alignment accuracy with PSI does not appear to be impacted by worsening preoperative varus deformity. All but one patient (96.9%) achieved neutral postoperative alignment relative to the predicted target axis. LEVEL OF EVIDENCE: Level IV, Clinical Case Series.

Intramedullary Fixation of Distal Fibula Fractures.

BACKGROUND: Ankle fractures pose a unique challenge to the treating orthopedic surgeon. Intramedullary (IM) distal fibula fixation is a relatively newer entity offering a viable option to minimize wound complications while providing similar outcomes. Our study utilizes an IM nail featuring proximal fixation via IM talons ensuring maintenance of fracture reduction this is the largest case series utilizing this novel device assessing time to weight-bearing (WB) and fracture union in addition to the safety and reproducibility of percutaneous reduction. METHODS: A retrospective case series was conducted on 51 ankle fractures treated with a single IM device for lateral malleolar fixation. Postoperative radiographs were assessed, qualifying reductions as good, fair, or poor based on a reduction classification. Patient charts were reviewed for fracture characteristics, reduction method, fracture union, time to WB, and complications. RESULTS: Mean follow-up time was 32.2 weeks; 47 fracture reductions (92%) were classified as good, and 4 (8%) were fair. All but 1 fracture (98%) went onto union. Average time to union was 10.3 weeks. Average time to WB with and without a walking boot was 6.8 and 11.2 weeks, respectively. Two patients experienced painful hardware. One patient had a superficial wound infection. CONCLUSION: When evaluating this novel IM device, fracture union and time to union were found to be acceptable, with minimal wound or other complications. Percutaneous reduction permitted good fracture reduction quality. Consistent time to WB for a variety of fractures was reliably demonstrated following operative fixation with this device, including those in the elderly population. LEVELS OF EVIDENCE: Level IV: Clinical case series.

Early Results of a Novel Intramedullary Fixation Device for Proximal Fifth Metatarsal Fractures.

BACKGROUND: Proximal fifth metatarsal fractures are commonly treated surgically due to their poor healing capacity. While intramedullary screws may be the most popular operative treatment choice, newer fixation methods continue to develop. We present a case series utilizing a novel intramedullary fixation device for proximal fifth metatarsal fractures. To our knowledge, no other study in the literature has assessed the safety and efficacy of this fixation method. METHODS: A retrospective analysis was performed for 16 patients with proximal fifth metatarsal fractures who underwent fixation with the same novel intramedullary device. Patient charts were reviewed for fracture union, plantar fracture gapping, time to weight-bearing, refracture, perioperative complications, and secondary surgeries. RESULTS: Sixteen patients with an average age of 43.3 years underwent fixation with this novel device from 2015 to 2020. Mean follow-up was 32.4 weeks. Fifteen of the 16 patients achieved radiographic union at a mean of 8.9 weeks. One patient suffered a nonunion. Mean time to full weight-bearing in, and out of, a walking boot was 6.4 and 9.8 weeks, respectively, for healed fractures. Mean plantar fracture gap improved from 1.22 mm to 0.88 mm following surgery. There were zero infections, refractures, or hardware complications. Three patients suffered iatrogenic fracture during implant insertion. CONCLUSION: To our knowledge, this is the first report of early results for this novel intramedullary device. Excellent union rates, acceptable time to weight-bearing, and a low complication profile can be achieved. Based on our findings, we propose a safe and effective treatment option for proximal fifth metatarsal fractures. LEVELS OF EVIDENCE: Level IV: Clinical case series.

Direct Plantar Approach to Plantar Plate Repair and Associated Wound Complications.

BACKGROUND: Lesser toe metatarsophalangeal joint (MTPJ) instability, secondary to plantar plate tear, has been the focus of numerous recent publications, the majority reporting on repair through a dorsal approach. A plantar approach has been described with the advantage of direct ligamentous repair or repair to bone, which follows conventional techniques employed throughout the body. Previous clinical studies have shown success in deformity correction and the longevity of both approaches. The proponents of the dorsal approach advocate that indirect repair of the plantar plate avoids perceived risks of complications with a plantar incision without evidence of superior outcomes. The purpose of this study was to investigate the safety and efficacy of the direct plantar approach to plantar plate repairs (PPRs) by reporting the rate of specific complications in a large clinical series. METHODS: This was the institutional review board (IRB) approved retrospective study of 204 PPRs in 185 patients (194 lesser MTP, 10 hallux MTP) with an average age of 56 and a mean body mass index (BMI) of 28. Surgical technique involved repair with absorbable braided suture (88%) versus suture anchor (12%) with or without MTPJ pinning (80%). Mean follow up was 53 weeks (range 5-170). Patients were screened for associated risk factors, including diabetes mellitus (8%), tobacco use (5%), neuropathy (1%), and additional concurrent procedures (96%). Complications were defined as superficial or deep infection, painful scars, and reoperation. Analysis was conducted using the Wilcoxon-Mann-Whitney test or Fisher's exact tests for continuous and categorical variables, respectively. Risk factors were analyzed using univariate logistic analysis to produce odds ratios (OR) with a 95% confidence interval (CI) and an inclusion criterion of a P-value, P > .2 for multivariate analysis as determined by Wald tests (significance at P < .05 for final modeling). RESULTS: Overall, there were 31 total complications (15%) demonstrated by 14 superficial infections (6.8%) and 17 painful scars (8.3%) along with three reoperations (1.4%). All reoperations were performed for deformity or instability, not scar revision. There were no deep infections. No increased odds of complications were found with suture anchor repair, MTPJ pinning, neuropathy, or diabetes. Patients that used tobacco had 7.5 (CI 1.66, 34.06) the odds of developing any wound complication compared with nonsmokers. Tobacco use was also found to significantly increase the odds of superficial infection by 9.8 (CI 2.08, 46.15). There was no increase in painful scars or reoperation in tobacco users. This study did not find an increased complication rate with additional ipsilateral procedures performed at the time of surgery. CONCLUSION: To our knowledge, this is the largest study evaluating the direct plantar approach to PPR as well as the evaluation of associated complications with the plantar incision. With low complication and minimal reoperation rates, the results of this study have demonstrated the clinical viability of plantar-based incisions. Previous studies have demonstrated the success of PPR and correction of deformity with a direct approach. This case series further demonstrates the safety and efficacy of plantar-based incisions, particularly for direct PPRs. LEVEL OF EVIDENCE: IV Retrospective Case Series. CATEGORY: Lesser Toes.

A model for evaluating the biomechanics of rib fracture fixation.

INTRODUCTION: High rates of morbidity and mortality following flail chest rib fractures are well publicized. Standard of care has been supportive mechanical ventilation, but serious complications have been reported. Internal rib fixation has shown improvements in pulmonary function, clinical outcomes, and decreased mortality. The goal of this study was to provide a model defining the biomechanical benefits of internal rib fixation. METHODS: One human cadaver was prepared with an actuator providing anteroposterior forces to the thorax and rib motion sensors to define interfragmentary motion. Cadaveric model was validated using a prior study which defined costovertebral motion to create a protocol using similar technology and procedure. Ribs 4-6 were fixed with motion sensors anteriorly, laterally and posteriorly. Motion was recorded with ribs intact before osteotomizing each rib anteriorly and laterally. Flail chest motion was record with fractures subsequently plated and analyzed. Motion was recorded in the sagittal, coronal and transverse axes. FINDINGS: Compared to the intact rib model, the flail chest model demonstrated an 11.3 times increase in sagittal plane motion, which was reduced to 2.1 times the intact model with rib plating. Coronal and sagittal plane models also saw increases of 9.7 and 5.1 times, respectively, with regards to flail chest motion. Both were reduced to 1.2 times the intact model after rib plating. INTERPRETATION: This study allows quantification of altered ribcage biomechanics after flail chest injuries and suggests rib plating is useful in restoring biomechanics as well as contributing to improving pulmonary function and clinical outcomes.

Viability and development of Ascaridia galli eggs recovered in artificial media followed by storage under different conditions.

Eggs oviposited by Ascaridia galli females in artificial media are commonly used as a source of infective material. We investigated the rate of egg production by cultured mature females (n = 223), and changes in egg viability under different storage and incubation conditions. Eggs recovered after 1, 2 or 3 days of culture were subjected to either (1) storage in water at 4°C (1, 4 or 8 weeks) followed by incubation in 0.1 N H2SO4 at 26°C (2, 4 or 6 weeks); or (2) prolonged storage at 4°C (up to 14 weeks). Egg development and viability was assessed by morphology coupled with a viability dye exclusion test of hatched larvae. Of the 6,044 eggs recovered per mature female 49.2, 38.5 and 12.3% were recovered on days 1, 2 and 3 of worm incubation respectively with similar initial viability (≥99%) between days. Eggs recovered on different days had only minor differences in viability after storage. The prolonged storage period at 4°C significantly affected both viability and embryonation ability resulting in decline in viability of 5.7-6.2% per week. A smaller but significant decline in egg (2.0%) and hatched larval (1.4%) viability per week of incubation at 26°C was also observed. We conclude that storage and incubation conditions, not the day of egg recovery, are the main factors affecting A. galli egg viability. Our findings indicate that under aerobic conditions storage at 26°C may be preferable to 4°C whereas other studies indicate that under anaerobic conditions storage at 4°C is preferable.

Posterior Ankle Impingement and Flexor Hallucis Longus Pathology.

Posterior ankle pain is a common complaint, and the potential causative pathologic processes are diverse. The constellation of these numerous etiologies has been collectively referred to as posterior ankle impingement syndrome. The pain associated with posterior ankle impingement is caused by bony or soft tissue impingement of the posterior ankle while in terminal plantar flexion. This condition is most frequently encountered in athletes who participate in sports that involve forceful, or repetitive, ankle plantar flexion. This article discusses the associated pathology, diagnosis, conservative treatment, and surgical techniques associated with flexor hallucis longus and posterior ankle impingement syndrome.

Topical wound anaesthesia: efficacy to mitigate piglet castration pain.

OBJECTIVE: There is a critical need for safe and effective analgesic treatments to address pain resulting from surgical husbandry procedures in livestock. Piglet castration results in acute pain and stress to the animal; however, it is performed globally on millions of piglets annually, often without any analgesia what-so-ever. Tri-Solfen® (Animal Ethics Pty Ltd, Yarra Glen, Victoria, Australia) is a combination local anaesthetic and antiseptic formulation which, applied topically to wounds, has proven effective, and is registered for use to alleviate pain associated with castration (and other wounds) in lambs and calves in Australia and New Zealand. It is also reported to be effective to reduce pain in piglets following castration. DESIGN: This randomised, blinded, placebo-controlled study examined the safety and efficacy of the formulation, administered via an adapted wound instillation method, to control pain both during and following piglet castration. METHOD: Piglets received Tri-Solfen or placebo, instilled to the wound immediately following skin incision. A 30 s wait period was then observed prior to completing castration. Pain mitigation was assessed by grading nociceptive resistance movements and piglet vocal response during castration, as well as by grading response to mechanical sensory stimulation of the wound (von Frey and needlestick) following castration. RESULTS: There was a significant reduction in nociceptive motor and vocal response during castration and in response to mechanical sensory wound stimulation up to and including 2 h following castration. There were no adverse events. CONCLUSION: Administered via this method, Tri-Solfen is effective to mitigate acute peri-operative castration pain in piglets.

Using repeated exposure through hands-on cooking to increase children's preferences for fruits and vegetables.

Few children in the United States meet national fruit and vegetable intake recommendations, highlighting a need for interventions. Children's food preferences act as a barrier to fruit and vegetable consumption, but prior research has demonstrated that repeated taste exposures can increase children's acceptance of these foods. Prior research in this area has typically utilized controlled procedures in which children sample small tastes of target foods over repeated occasions. The primary aim of the present pilot study was to test whether children's preferences for target fruits and vegetables increased following repeated taste exposures to them through hands-on cooking in a community setting. Seventeen 6-to-8-year-old children participated in biweekly study sessions during six weeks of a summer camp serving lower-income families. Liking of (yummy, just OK, yucky) and rank-ordered preferences for nine fruits and vegetables were measured before and after exposure sessions (pre-test and post-test). Based on pre-test assessments, four relatively less liked foods (two fruits, two vegetables) were chosen to become target foods. Children were then exposed to target foods during nine hands-on cooking sessions; liking of target foods was also measured at a midpoint assessment. At each exposure session, children assisted with preparation of a different snack using a recipe involving target foods and then ate the prepared snack together. Preferences for target foods increased from pre-test (Median = 5.8) to post-test (Median = 5.5; p < 0.05). On average, the majority of children rated the prepared snacks favorably. Results from this pilot study demonstrate the potential of applying repeated exposure techniques via hands-on cooking in a community setting.

Experience of prehospital emergency care among general practitioners in Ireland.

BACKGROUND: Although widely acknowledged, few data exist on the scope of general practice involvement in the management of prehospital emergencies. A study was undertaken to explore the frequency and types of emergencies dealt with and the interventions undertaken by GPs who had completed Immediate Care training. METHODS: All participants in Immediate Care courses in Ireland in 2002, 2003 and 2004 were invited to complete an anonymised questionnaire in which they estimated their experience of emergencies since completing a course. Sections dealt with personal/practice information, types of emergencies, interventions used and follow-up training. RESULTS: 448 participants completed courses, 408 were available to participate in the study and 259 (63.5%) responded; 66.6% of GPs responded. The mean reporting period was 29.4 months (range 18-53). Participants included many younger female GPs at the start of their general practice careers. Although most emergencies dealt with were medical, few other patterns emerged in the timing or setting of emergencies. 88% of GPs had called an ambulance in an emergency at least once in the preceding year. 84% of GPs had managed a suspected acute myocardial infarction at least once during the reporting period; seizures, serious injuries, paediatric emergencies and hypoglycaemia were dealt with by up to half of all GPs. Interventions used included intravenous access in a medical emergency (69%), intravenous fluid administration (51%), intravenous morphine (54%), cardiopulmonary resuscitation (37%), defibrillation (21%), use of airway adjuncts (28%) and use of advanced life support drugs in cardiac arrest (24%). CONCLUSIONS: GPs make frequent use of a wide range of interventions in prehospital emergencies. Issues relating to tailored training, adequate equipment, collaboration with the emergency services and skills maintenance are highlighted by these data.

Solution structures of two CCHC zinc fingers from the FOG family protein U-shaped that mediate protein-protein interactions.

BACKGROUND: Zinc finger domains have traditionally been regarded as sequence-specific DNA binding motifs. However, recent evidence indicates that many zinc fingers mediate specific protein-protein interactions. For instance, several zinc fingers from FOG family proteins have been shown to interact with the N-terminal zinc finger of GATA-1. RESULTS: We have used NMR spectroscopy to determine the first structures of two FOG family zinc fingers that are involved in protein-protein interactions: fingers 1 and 9 from U-shaped. These fingers resemble classical TFIIIA-like zinc fingers, with the exception of an unusual extended portion of the polypeptide backbone prior to the fourth zinc ligand. [15N,(1)H]-HSQC titrations have been used to define the GATA binding surface of USH-F1, and comparison with other FOG family proteins indicates that the recognition mechanism is conserved across species. The surface of FOG-type fingers that interacts with GATA-1 overlaps substantially with the surface through which classical fingers typically recognize DNA. This suggests that these fingers could not contact both GATA and DNA simultaneously. In addition, results from NMR, gel filtration, and sedimentation equilibrium experiments suggest that the interactions are of moderate affinity. CONCLUSIONS: Our results demonstrate unequivocally that zinc fingers comprising the classical betabetaalpha fold are capable of mediating specific contacts between proteins. The existence of this alternative function has implications for the prediction of protein function from sequence data and for the evolution of protein function.

Long-term clinical and angiographic outcomes in symptomatic patients with 70% to 99% carotid artery stenosis.

BACKGROUND AND PURPOSE: In 1991, the North American Symptomatic Carotid Endarterectomy Trial (NASCET) reported the benefit of carotid endarterectomy for 659 patients with 70% to 99% stenosis. Follow-up continued until 1997. METHODS: The present study examined the risks and causes of ipsilateral stroke in the randomized groups and in those who had delayed endarterectomy or continued on medical therapy and also examined the evolution of carotid disease on follow-up imaging. RESULTS: By on-treatment (efficacy) analysis, the risk of any ipsilateral stroke at 3 years was 28.3% for medically randomized and 8.9% for surgically randomized patients (19.4% absolute risk reduction, P:<0.001). For combined disabling or fatal ipsilateral stroke, the risks were 14.0% and 3.4%, respectively (10. 6% absolute risk reduction). In medical patients, >80% of the first strokes at 3 years were of large-artery origin. After February 1991, 116 suitable medical patients underwent endarterectomy within 6 months, and 115 continued on medical therapy. The 3-year risk of any ipsilateral stroke in the groups of 116 and 115 patients was 7.9% and 15.0%, respectively (7.1% absolute risk reduction). During follow-up, 81 patients had angiograms comparable to the baseline images. Progression by >/=10% occurred in 7 patients; regression, in 8; no change, in 39; and occlusion, in 27. By use of both angiography and ultrasound, 63 (25.5%) of the 247 medically treated patients progressed to occlusion, of whom 31.7% had an ipsilateral stroke before or on the day of occlusion. CONCLUSIONS: Endarterectomy for patients with 70% to 99% stenosis and recent symptoms was efficacious in the long term. Compared with patients who continued on medical therapy, medical patients with delayed endarterectomy experienced a moderate benefit. Medically treated patients experienced a high risk of occlusion.

The causes and risk of stroke in patients with asymptomatic internal-carotid-artery stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators.

BACKGROUND: The causes of stroke in patients with asymptomatic carotid-artery stenosis have not been carefully studied. Information about causes might influence decisions about the use of carotid endarterectomy in such patients. METHODS: We studied patients with unilateral symptomatic carotid-artery stenosis and asymptomatic contralateral stenosis from 1988 to 1997. The causes, severity, risk, and predictors of stroke in the territory of the asymptomatic artery were examined and quantified. RESULTS: The risk of stroke at five years after study entry in a total of 1820 patients increased with the severity of stenosis. Among 1604 patients with stenosis of less than 60 percent of the luminal diameter, the risk of a first stroke was 8.0 percent (1.6 percent annually), as compared with 16.2 percent (3.2 percent annually) among 216 patients with 60 to 99 percent stenosis. In the group with 60 to 99 percent stenosis, the five-year risk of stroke in the territory of a large artery was 9.9 percent, that of lacunar stroke was 6.0 percent, and that of cardioembolic stroke 2.1 percent. Some patients had more than one stroke of more than one cause. In the territory of an asymptomatic occluded artery (as was identified in 86 patients), the annualized risk of stroke was 1.9 percent. Strokes with different causes had different risk factors. The risk factors for large-artery stroke were silent brain infarction, a history of diabetes, and a higher degree of stenosis; for cardioembolic stroke, a history of myocardial infarction or angina and hypertension; for lacunar stroke, age of 75 years or older, hypertension, diabetes, and a higher degree of stenosis. CONCLUSIONS: The risk of stroke among patients with asymptomatic carotid-artery stenosis is relatively low. Forty-five percent of strokes in patients with asymptomatic stenosis of 60 to 99 percent are attributable to lacunes or cardioembolism. These observations have implications for the use of endarterectomy in asymptomatic patients. Without analysis of the risk of stroke according to cause, the absolute benefit associated with endarterectomy may be overestimated.

The transactivation domain within cysteine/histidine-rich region 1 of CBP comprises two novel zinc-binding modules.

cAMP-response element-binding protein-binding protein (CBP) is a transcriptional coactivator that interacts with a number of DNA-binding proteins and cofactor proteins involved in the regulation of transcription. Relatively little is known about the structure of CBP, but it has been noted that it contains three domains that are rich in cysteine and histidine (CH1, CH2, and CH3). The sequence of CH2 conforms to that of a leukemia-associated protein domain (PHD finger), and it has been postulated that this and both CH1 and CH3 may be zinc finger domains. This has not, however, been demonstrated experimentally. We have studied CH1 and show that it is composed of two novel zinc-binding modules, which we term "zinc bundles." Each bundle contains the sequence Cys-X(4)-Cys-X(8)-His-X(3)-Cys, and we show that a synthetic peptide comprising one zinc bundle from CH1 can fold in a zinc-dependent manner. CH3 also appears to contain two zinc bundles, one with the variant sequence Cys-X(2)-Cys-X(9)-His-X(3)-Cys, and we demonstrate that this variant motif also undergoes Zn(II)-induced folding. CH1 acts as a transcriptional activation domain in cellular assays. We show that mutations in any of the four zinc-chelating residues in either zinc bundle of CH1 significantly impair this activity and that these mutations also interfere with certain protein-protein interactions mediated by CH1. Our results indicate that CBP is a genuine zinc-binding protein and introduce zinc bundles as novel protein interaction domains.

Causes and severity of ischemic stroke in patients with internal carotid artery stenosis.

CONTEXT: Therapeutic trials generally have not distinguished outcomes of stroke according to cause. OBJECTIVE: To determine whether stroke and subsequent disability was of large-artery, lacunar, or cardioembolic origin in patients with different degrees of symptomatic and asymptomatic carotid stenosis. DESIGN: Observational study of prospective data collected from the North American Symptomatic Carotid Endarterectomy Trial between 1987 and 1997. SETTING AND PATIENTS: A total of 2885 patients from 106 sites in the United States and abroad (median age, 67 years; 70% male) who had symptomatic internal carotid artery stenosis. MAIN OUTCOME MEASURE: Risk of stroke from each of the 3 causes at 5 years by territory and degree of stenosis. RESULTS: During an average follow-up of 5 years, 749 patients had 1039 strokes, including 112 of cardioembolic, 211 of lacunar, 698 of large-artery, 17 of primary intracerebral hemorrhage, and 1 of subarachnoid hemorrhage origin. The 5-year risk of first stroke after entry into the trial in any territory was 2.6% of cardioembolic cause, 6.9% of lacunar cause, and 19.7% of large-artery cause. The proportion of cardioembolic strokes in the territory of the symptomatic artery was 12.0% and 6.9% in 60% to 69% and 70% to 99% arterial stenosis, respectively; large-artery strokes predominated (78.4%) at 70% to 99% arterial stenosis. With 70% to 99% arterial stenosis, the proportion of strokes of cardioembolic and lacunar origin was 43.5% and 21.6% in asymptomatic and symptomatic arteries, respectively. A total of 67.6% of cardioembolic, 16.7% of lacunar, and 33.0% of large-artery strokes in the territory of the asymptomatic artery were disabling or fatal. CONCLUSIONS: Our data suggest that approximately 20% and 45% of strokes in the territory of symptomatic and asymptomatic carotid arteries with 70% to 99% stenosis, respectively, are unrelated to carotid stenosis. The cause of subsequent strokes in similar types of patients should be considered when making treatment decisions involving carotid endarterectomy for patients with asymptomatic carotid stenosis, since lacunar and cardioembolic strokes cannot be prevented by endarterectomy.

A class of zinc fingers involved in protein-protein interactions biophysical characterization of CCHC fingers from fog and U-shaped.

Zinc fingers (ZnFs) are extremely common protein domains. Several classes of ZnFs are distinguished by the nature and spacing of their zinc-coordinating residues. While the structure and function of some ZnFs are well characterized, many others have been identified only through their amino acid sequence. A number of proteins contain a conserved C-X2-C-X12-H-X1-5-C sequence, which is similar to the spacing observed for the 'classic' CCHH ZnFs. Although these domains have been implicated in protein-protein (and not protein-nucleic acid) interactions, nothing is known about their structure or function at a molecular level. Here, we address this problem through the expression and biophysical characterization of several CCHC-type zinc fingers from the erythroid transcription factor FOG and the related Drosophila protein U-shaped. Each of these domains does indeed fold in a zinc-dependent fashion, coordinating the metal in a tetrahedral manner through the sidechains of one histidine and three cysteine residues, and forming extremely thermostable structures. Analysis of CD spectra suggests an overall fold similar to that of the CCHH fingers, and indeed a point mutant of FOG-F1 in which the final cysteine residue is replaced by histidine remains capable of folding. However, the CCHC (as opposed to CCHH) motif is a prerequisite for GATA-1 binding activity, demonstrating that CCHC and CCHH topologies are not interchangeable. This demonstration that members of a structurally distinct subclass of genuine zinc finger domains are involved in the mediation of protein-protein interactions has implications for the prediction of protein function from nucleotide sequences.

Risk factors and outcome of patients with carotid artery stenosis presenting with lacunar stroke. North American Symptomatic Carotid Endarterectomy Trial Group.

OBJECTIVE: To examine the relationship between carotid artery stenosis, other risk factors, and lacunar stroke. BACKGROUND: Carotid artery stenosis in patients presenting with lacune stroke may be coincidental or causal. The distinction by risk factor profile is uncertain. The risk and cause of subsequent stroke, and benefit of carotid endarterectomy (CE) is unknown. METHODS: Stroke in patients entering the North American Symptomatic Carotid Endarterectomy Trial were classified as nonlacunar, possible lacune (symptoms without CT lacunae), or probable lacune (symptoms with CT lacunae). RESULTS: Of 1,158 patients with hemispheric stroke, 493 had features of lacunar stroke (283 possible and 210 probable). Lacunar stroke presented more commonly in patients with milder (<50%) degrees of internal carotid artery (ICA) stenosis (p = 0.003). History of diabetes and hyperlipidemia, not hypertension, were associated independently even after accounting for the degree of stenosis. Medically treated patients presenting with nonlacunar stroke had a low risk of subsequent lacunar events of 2.9% at 3 years in comparison with 9.2% for probable lacunar presentation (p = 0.03). For patients with 50 to 99% ICA stenosis, the relative risk reductions (RRRs) in stroke from CE were 35% when the presenting stroke was probable lacunar versus 61% when the stroke was nonlacunar. Patients presenting with a possible lacunar stroke had a 53% RRR. CONCLUSIONS: History of diabetes and hyperlipidemia were more important than arterial hypertension as risk factors for patients with lacunar stroke. Patients presenting with lacunar stroke more often had milder ICA stenosis. Although CE reduced the risk of stroke in all patients with 50 to 99% ICA stenosis, lesser benefits were observed in patients presenting with lacunar stroke.

Importance of intracranial atherosclerotic disease in patients with symptomatic stenosis of the internal carotid artery. The North American Symptomatic Carotid Endarterectomy Trail.

BACKGROUND AND PURPOSE: The estimated prevalence of intracranial atherosclerotic disease (IAD) in patients with stenosis of the extracranial internal carotid artery (ICA) varies between 20% and 50%. The benefits of carotid endarterectomy (CE) in patients with both IAD and symptomatic extracranial ICA stenosis are uncertain. METHODS: The association between IAD and other vascular risk factors and with the risk of stroke at 3 years were studied in patients with symptomatic extracranial ICA stenosis who participated in the North American Symptomatic Carotid Endarterectomy Trial (NASCET). Since the NASCET protocol excluded severe IAD, only a modest number of patients in this category could be studied. RESULTS: IAD was observed in one third of the patients. In medically treated patients, the relative risk of stroke associated with IAD varied from 1.3 (95% CI, 0.9 to 1.9) with extracranial ICA stenosis of <50% to 1.8 (95% CI, 1.1 to 3.2) with 85% to 99% ICA stenosis. In contrast, IAD did not affect the risk of stroke among surgically treated patients. To prevent 1 stroke ipsilateral to the symptomatic ICA stenosis over 3 years in patients who have also IAD, 12 patients with 50% to 69%, 5 patients with 70% to 84%, and 3 patients with 85% to 99% ICA stenosis have to undergo CE. In patients without IAD these numbers are 26, 7, and 6, respectively. CONCLUSIONS: IAD is an independent risk factor for subsequent stroke in medically treated patients with symptomatic ICA stenosis. CE reduces this risk. The additional risk imposed by IAD in medically treated patients enhances the value of CE in patients with moderate symptomatic extracranial ICA stenosis. Detection of IAD, requiring angiography, is an important prelude to planning CE in symptomatic patients with moderate extracranial ICA stenosis.

TAT results in a longitudinal study of bereaved college students.

The authors analyzed projective data obtained from 141 college students who wrote stories on three separate occasions to selected cards from the Thematic Apperception Test (TAT). The students included 46 members of support groups for bereaved college students, 34 members of a bereavement control group, and 61 nonbereaved students. The study used a repeated-measures pretest-posttest control group design to gather longitudinal data about the trajectory of bereavement with and without support group intervention. Coders, who reached consistently high interrater reliability, looked for themes of death, grief, coping, and affiliation in the stories. Multivariate analysis of variance (MANOVA) and repeated-measures MANOVA tests were applied to analyze coding results. Overall MANOVA results indicated significant group differences in the responses to the TAT cards. Repeated-measures MANOVA found group differences in use of themes of death and grief and found Group x Time differences in maintaining a sense of self-efficacy while in a crisis. A majority of the stories contained affiliation imagery but without any group differences in the use of such imagery.

Carotid artery stenosis: external validity of the North American Symptomatic Carotid Endarterectomy Trial measurement method.

PURPOSE: To assess the generalizability of the North American Symptomatic Carotid Endarterectomy Trial method for determining the degree of stenosis on angiograms. MATERIALS AND METHODS: Six good-quality, baseline angiograms of carotid arteries that were less than 70% stenosed were reviewed by 14 experienced neuroradiologists at different academic institutions. All reviewers determined the degree of stenosis by calculating the ratio of the diameter of the artery at the point of maximal narrowing to the normal diameter distal to the stenosis (well beyond the carotid artery bulb). The reviewers marked the location of their measurements on the angiogram. Comparisons were performed among the reviewers' results and with the reference measurements. RESULTS: Interobserver agreement was 0.84 (95% confidence interval = 0.65, 0.97). The average interobserver disagreement of +/-7% was comparable with that reported in the literature. The overall bias was 6%, which indicated a tendency of the reviewers to overestimate the degree of stenosis in comparison with the reference determination. CONCLUSION: The North American Symptomatic Carotid Endarterectomy Trial reference measurements can be generalized beyond the bounds of this clinical trial, provided that attention is paid to details of the measurement method.