Genetic variation in the serotonin transporter modulates neural system-wide response to fearful faces.

A distributed, serotonergically innervated neural system comprising extrastriate cortex, amygdala and ventral prefrontal cortex is critical for identification of socially relevant emotive stimuli. The extent to which a genetic variation of serotonin transporter gene 5-HTTLPR impacts functional connectivity between the amygdala and the other components of this neural system remains little examined. In our study, neural activity was measured using event-related functional magnetic resonance imaging in 29 right-handed, white Caucasian healthy subjects as they viewed mild or prototypical fearful and neutral facial expressions. 5-HTTLPR genotype was classified as homozygous for the short allele (S/S), homozygous for the long allele (L/L) or heterozygous (S/L). S/S showed greater activity than L/L within right fusiform gyrus (FG) to prototypically fearful faces. To these fearful faces, S/S more than other genotype subgroups showed significantly greater positive functional connectivity between right amygdala and FG and between right FG and right ventrolateral prefrontal cortex (VLPFC). There was a positive association between measure of psychoticism and degree of functional connectivity between right FG and right VLPFC in response to prototypically fearful faces. Our data are the first to show that genotypic variation in 5-HTTLPR modulates both the amplitude within and the functional connectivity between different components of the visual object-processing neural system to emotionally salient stimuli. These effects may underlie the vulnerability to mood and anxiety disorders potentially triggered by socially salient, emotional cues in individuals with the S allele of 5-HTTLPR.

Neural responses to dynamic expressions of fear in schizophrenia.

Abnormalities in social functioning are a significant feature of schizophrenia. One critical aspect of these abnormalities is the difficulty these individuals have with the recognition of facial emotions, particularly negative expressions such as fear. The present work focuses on fear perception and its relationship to the paranoid symptoms of schizophrenia, specifically, how underlying limbic system structures (i.e. the amygdala) react when probed with dynamic fearful facial expressions. Seven paranoid and eight non-paranoid subjects (all males) with a diagnosis of schizophrenia took part in functional magnetic resonance imaging study (1.5T) examining neural responses to emerging fearful expressions contrasted with dissipating fearful expressions. Subjects viewed emerging and dissipating expressions while completing a gender discrimination task. Their brain activation was compared to that of 10 healthy male subjects. Increased hippocampal activation was seen in the non-paranoid group, while abnormalities in the bilateral amygdalae were observed only in the paranoid individuals. These patterns may represent trait-related hippocampal dysfunction, coupled with state (specifically paranoia) related amygdala abnormalities. The findings are discussed in light of models of paranoia in schizophrenia.

Lateralisation of language function in young adults born very preterm.

OBJECTIVE: To explore, using functional magnetic resonance imaging (MRI), the functional organisation of phonological processing in young adults born very preterm. SUBJECTS: Six right handed male subjects with radiological evidence of thinning of the corpus callosum were selected from a cohort of very preterm subjects. Six normal right handed male volunteers acted as controls. METHOD: Blood oxygenation level dependent contrast echoplanar images were acquired over five minutes at 1.5 T while subjects performed the tasks. During the ON condition, subjects were visually presented with pairs of non-words and asked to press a key when a pair of words rhymed (phonological processing). This task alternated with the OFF condition, which required subjects to make letter case judgments of visually presented pairs of consonant letter strings (orthographic processing). Generic brain activation maps were constructed from individual images by sinusoidal regression and non-parametric testing. Between group differences in the mean power of experimental response were identified on a voxel wise basis by analysis of variance. RESULTS: Compared with controls, the subjects with thinning of the corpus callosum showed significantly reduced power of response in the left hemisphere, including the peristriate cortex and the cerebellum, as well as in the right parietal association area. Significantly increased power of response was observed in the right precentral gyrus and the right supplementary motor area. CONCLUSIONS: The data show evidence of increased frontal and decreased occipital activation in male subjects with neurodevelopmental thinning of the corpus callosum, which may be due to the operation of developmental compensatory mechanisms.

Exploring the social brain in schizophrenia: left prefrontal underactivation during mental state attribution.

OBJECTIVE: Evidence suggests that patients with schizophrenia have a deficit in "theory of mind," i.e., interpretation of the mental state of others. The authors used functional magnetic resonance imaging (MRI) to investigate the hypothesis that patients with schizophrenia have a dysfunction in brain regions responsible for mental state attribution. METHOD: Mean brain activation in five male patients with schizophrenia was compared to that in seven comparison subjects during performance of a task involving attribution of mental state. RESULTS: During performance of the mental state attribution task, the patients made more errors and showed less blood-oxygen-level-dependent signal in the left inferior frontal gyrus. CONCLUSIONS: To the authors' knowledge, this is the first functional MRI study to show a deficit in the left prefrontal cortex in schizophrenia during a socioemotional task.

Acute renal failure related to rhabdomyolysis: pathophysiology, diagnosis, and collaborative management.

Acute renal failure related to exertional rhabdomyolysis is a medical condition that, if not diagnosed correctly and treated aggressively, can lead to serious dysfunction and may result in death. Although the history is invaluable in diagnosing this condition, it must be confirmed by laboratory testing. The sometimes subtle manifestations of exertional (non-traumatic) rhabdomyolysis make it mandatory that the health care team is able to recognize the signs and symptoms and understand the pathophysiology for prompt treatment and referral.

Access thrombosis, hospitalization, and hematocrit level in hemodialysis patients.

Are occurrences of vascular access thrombosis and hospitalization higher in hemodialysis patients with hematocrits (Hcts) > 36% compared to those < 36%? This 12-month retrospective study included 30 male hemodialysis patients who received erythropoietin (rHuEPO) for at least 6 months. Sixty percent (n = 18) had arteriovenous fistulas and 40% (n = 12) had polytetrafluoroethylene grafts. The mean age was 59.6 years. Twenty patients during 216 patient months had a mean Hct < 36% with five thromboses (2.3%). Ten patients during 118 patient months had a mean Hct > 36% with four thromboses (3.4%). There was no statistically significant difference between the thrombosis rates in the two groups. There were four hospitalizations in 118 patient months in the > 36% group (3.4%). There were 33 hospitalizations in 216 patient months in the < 36% group (15.3%). This is 4.5 times higher than the > 36% group. Our data suggest that Hcts > 36% are not associated with increased thrombosis and are associated with lower hospitalization rates.

Vaginal gonococcal cultures in sexual abuse evaluations: evaluation of selective criteria for preteenaged girls.

OBJECTIVE: Accurate selective criteria could limit the number of vaginal cultures for Neisseria gonorrhoeae performed on preteenaged girls as part of their sexual abuse evaluations. This study was performed to determine whether the published selective criteria by the American Academy of Pediatrics (AAP) Committee on Child Abuse and Neglect and by Siegel et al would have accurately detected all cases of vaginal gonococcal infections in our large study population. METHODS: We prospectively studied girls, ages 1 to 12 years, who were referred to our Child Sexual Abuse Team (CSAT) at Wake Medical Center in Raleigh, NC, between July 1, 1976 to July 1, 1996, for sexual abuse evaluations which were performed using a protocol that included collecting historical information, a sexual abuse interview, and a detailed genital examination which included a vaginal culture for N gonorrhoeae. RESULTS: Our study population consisted of 2898 girls of whom 2731 (94%) had vaginal cultures successfully performed for N gonorrhoeae. There were 84 girls with vaginal gonococcal infections, 80 of whom had a vaginal discharge. The four girls without a vaginal discharge included two with a history of having vaginal intercourse with an alleged perpetrator with gonorrhea, one with N gonorrhoeae isolated from a urine culture, and one whose preteenaged sister had gonorrhea. All of the 84 girls would have been identified using the selective culturing criteria of the AAP Committee on Child Abuse and Neglect: culturing when epidemiologically indicated (interpreted as the girl having another sexually transmitted disease [STD], a child sibling, child household member, a close child associate or a perpetrator with a known STD) or when the history and/or physical findings suggest the possibility of oral, genital, or rectal contact, or Siegel et al's more selective criteria: only culturing prepubertal girls for N gonorrhoeae if there is a vaginal discharge at the time of presentation or if there is a high risk for STD acquisition, defined as having a STD diagnosed, a sibling with a STD, contact with a perpetrator known to have a STD, contact with multiple perpetrators, or Tanner stage III or above. CONCLUSION: Both the selective criteria of the AAP Committee on Child Abuse and Neglect and the more selective criteria of Siegel et al as we interpreted them were accurate when applied to identifying girls with vaginal gonococcal infections in our study population.

Fibular head autograft. A salvage technique for severely comminuted lateral fractures of the tibial plateau: report of five cases.

Severely comminuted fractures of the lateral tibial plateau with central defects of the articular cartilage have traditionally been treated with iliac crest or patellar autograft, with varying success. Arthrodesis or arthroplasty for late deformity or instability are not suitable for young, active patients. The use of the fibular head as a replacement for the tibial plateau obtained excellent or good functional results in five patients with these difficult fractures.

Fatigue failure in small diameter tibial nails.

The prevalence of implant failure in small diameter tibial nails has not been well characterized. In a series of 130 tibial fractures stabilized with 8-mm and 9-mm nails, implant failure occurred in 18 fractures (13.8%): 4 nails (3%) broke and 16 (12.3%) screws failed. All nail failures occurred in open, unstable fractures with delayed union, and all of the nails that broke were dynamically locked during the failure. Of the 130 fractures, 128 (98.5%) eventually united. Delayed union, degree of comminution, metaphyseal location, and dynamic locking of unstable fractures contribute to hardware failure. Based on these findings, dynamization could be used to treat delayed union only in axially stable diaphyseal fractures. Exchange nailing is recommended to treat delayed union in comminuted or metaphyseal fractures to prevent hardware failure. Bone grafting should be performed at 6 to 12 weeks for fractures with > 50% bone loss.

Fractures of the proximal part of the femur.

The orthopaedic surgeon has a multitude of internal fixation devices and techniques available for use in the treatment of subtrochanteric fractures of the proximal femur. The successful use of second-generation locking nails is technically demanding. Close attention to positioning of the patient, reduction of the fracture, placement of the guide-wire, and insertion of the nail and of the proximal and distal locking screws is mandatory. The newer, high-strength hip-screws allow good fixation of a fracture that extends into the piriformis fossa. If medial comminution is present, this technique is best performed in conjunction with indirect reduction and bone-grafting. With proper technique, these devices allow the surgeon to manage predictably a complex subtrochanteric fracture that previously had to be treated with traction or extensive dissection and with (frequently inadequate) internal fixation.

Treatment of open fractures of the tibial shaft with the use of interlocking nailing without reaming.

Fifty open fractures of the tibial shaft that were treated with débridement and interlocking nailing without reaming were followed for an average of twelve months. Most of the fractures were the result of high-energy trauma, and 68 per cent of the fracture wounds were grade III. Forty-eight (96 per cent) of the fifty fractures united at an average of seven months; there were no malunions. There were four infections (8 per cent), all at the sites of grade-III fractures. Locking screws broke in five tibiae (10 per cent), but the breakage did not result in a loss of reduction. Three nails broke, two at the sites of ununited fractures and one at the site of a healed fracture. These results are comparable with, or better than, those obtained with other forms of fixation, including immobilization with a cast, unlocked intramedullary nailing, and external fixation.

Mechanical characterization of femoral interlocking intramedullary nailing systems.

The most important mechanical characteristics of a nailing system are related to its stiffness (rigidity) and strength. This study evaluates the properties of three commercially available interlocking intramedullary nail systems using standardized test methods. An understanding of the mechanical properties along with the clinical data will assist the surgeon in choosing the optimum implant. Testing indicates that the bending strength and stiffness of the Grosse & Kempf, the AO/ASIF Universal, and the Russell-Taylor interlocking intramedullary nail designs are comparable. It is therefore not surprising that all of these nail systems have excellent clinical results. However, the nonslotted design is approximately 30 times more resistant to torsional loading than either the partially slotted design of the Grosse & Kempf nail or the fully slotted design of the AO/ASIF nail. The clinical relevance of the torsional values may not be known until a long-term comparison of the complication rates for these different systems is available. Analysis of screw design reveals a tradeoff in bending strength when compared to amount of bone purchase. The bending strength of fully threaded screws (allowing bicortical fixation) is less than that of partially threaded screws (allowing only unicortical fixation), which shows that for the implants tested, increased bone purchase requires a compromise in strength for similar sized screws.

Percutaneous epiphysiodesis: experimental study and preliminary clinical results.

An experimental study was conducted to determine the feasibility of using percutaneous drilling and pneumatic burring under image intensification to effect premature closure of the distal femoral epiphyseal plate in immature New Zealand white rabbits. Serial roentgenograms were made before the animals were killed at 6 or 10 weeks to document leg length inequality as compared with the contralateral leg following the procedure. Microscopic examination of nonoperated and operated epiphyseal plate revealed complete arrest of the operated epiphysis with bone fusion at the epiphyseal plate in eight of the nine rabbits. Since this animal study, 13 children have undergone percutaneous epiphysiodesis. Roentgenographically, all the growth plates appeared fused following the procedure. However, complete growth arrest cannot be substantiated until skeletal maturity. This is a preliminary report of a procedure that needs further documentation.

Electrophoretic map of boar sperm plasma membrane polypeptides and localization and fractionation of specific polypeptide subclasses.

A high resolution, two-dimensional (2-D) electrophoretic map of the plasma membrane (PM) polypeptides from the ejaculated boar spermatozoon is described. 2-D silver-stained polyacrylamide gel electrophoresis (PAGE) gels revealed over 250 polypeptides; Coomassie blue staining revealed more than 100. Fifty Coomassie-staining polypeptides were catalogued and biochemically characterized, with twenty of these designated major sperm PM polypeptides. Cavitation pressures ranging from 50 PSI to 1000 PSI were used to enrich 2-D maps either in head PM (50 PSI) or in flagellar PM (1000 PSI) and provided tentative localization of certain PM polypeptides. Immunoabsorption chromatography showed that most major polypeptides seen in the 2-D map were antigenic. Major polypeptide bands from single dimensional (1-D) gels were excised, antibodies against them were produced in rabbits, and the polypeptides were localized via indirect fluorescein isothiocyanate (FITC) technique. Cross-reacting antigenic determinants in the PAGE PM polypeptides were determined by transblotting and staining the transblots by an indirect peroxidase technique. Cross-reactivity was extensive with several polypeptide groups, but specific enough with others to allow tentative localization. Lectin affinity chromatography using Con A, WGA, RCA-1, PNA, and DBA indicated the lectin specificity of PM polypeptides. These data together with periodic acid-Schiff (PAS) and carbohydrate-specific silver staining permitted identification of glycoproteins in the 2-D maps. FITC coupled to specific lectins showed the regional distribution of these lectins on the sperm surface. The 2-D polypeptide map and the catalogue of properties of major Coomassie-stained PM polypeptides provides a reference for future studies in the boar and other species.

Visualization of anti-sperm plasma membrane IgG and Fab as a method for localization of boar sperm membrane antigens.

A simple method for ultrastructural localization of sperm surface antigens by direct visualization of bound antibodies is presented. Anti-sperm plasma membrane (ASPM) immunoglobulin (Ig) G, visualized in tissues treated with an osmium:ferrocyanide mixture, projected 11-13 nm from the surface and ASPM Fab fragments projected 8-10 nm from the surface. The density of IgG labeling, as subjectively estimated, corresponded to indirect immune fluorescein isothiocyanate, indirect immunoferritin, and sperm-vesicle labeling patterns. Agglutination of sperm vesicles and sperm were demonstrated and the linking antibody visualized. A second antibody on protein A directed against ASPM IgG made the immunologic tag more apparent and indicated, in disrupted sperm preparations, labeling of both sides of the plasma membrane. The method provides for easy and sensitive localization of sperm surface antigens at the ultrastructural level and is presently being used to localize specific sperm antigens.