NMR Microscopy of Single Neurons Using Spin Echo and Line Narrowed 2DFT Imaging

NMR microimages of single neural cells were acquired at 500 MHz using a conventional spin echo pulse sequence and a line-narrowing sequence that eliminates susceptibility effects. The data show that any contribution to the measured T₂ relaxation rate arising from diffusion in local field inhomogeneities using spin echo sequences at high fields and high spatial resolution is relatively small. We conclude that the measured T₂ difference between the nucleus and cytoplasm in these cells represents primarily a true T₂ relaxation effect arising from the interactions of water with macromolecules in the two compartments and does not result from microsusceptibility differences. These observations have implications regarding water compartmentation in single cells and the interpretation of the MR characteristics of tissues in vivo.     

Immunohistologic parameters in minimal morphologic change duodenal biopsies from patients with clinically suspected gluten-sensitive enteropathy.

Subclinical or latent cases of gluten-sensitive enteropathy (GSE) are difficult to diagnose, and serology-positive, histology-negative (minimal morphologic change) and serology-negative, histology-positive patients have been identified. Both, particularly the histology-negative group, require the correct diagnosis for proper management, especially because the concept of minimal histologic change GSE has escaped attention in standard textbooks. We assessed the numbers and distribution of intraepithelial T cells and their subsets with CD3, CD8, and CD4 immunostaining and examined for crypt hyperplasia with mitotic and Ki-67 proliferative indices with the aim of refining the criteria for the diagnosis of minimal change GSE. Duodenal biopsies from 46 clinically suspected cases of GSE tested for antigliadin, antiendomysium, and antitissue transglutaminase antibodies were divided into four groups: serology-positive, histology-positive (S+H+, n = 20); serology-positive, histology-negative (S+H-, n = 22), representing the minimal morphologic change group; serology-negative, histology-positive (S-H+, n = 4); and serology-negative, histology-negative (S-H-, n = 28), controls with histologically normal duodenal biopsies obtained for unrelated reasons. The numbers of CD3+ and CD8+ intraepithelial T cells (IETCs) were significantly higher in histology-positive biopsies with (mean, 40.3/100 and 39.3/100 enterocytes, respectively) and without positive serology (mean, 33.3/100 and 35/100 enterocytes, respectively) compared with all other groups (S+H-, mean, 26.5/100 and 24.3/100 enterocytes, respectively; S-H-, mean, 23.3/100 and 17.9/100 enterocytes, respectively). Values for Ki-67 index in crypt enterocytes were also significantly different between histology-positive and histology-negative groups (P = 0.000). The distribution of CD3+ and CD8+ IETCs was mostly even along the surface enterocytes in histology-positive cases compared with the controls, which showed an uneven distribution. The 2 parameters that significantly discriminated between minimal morphologic change GSE (S+H-) and controls (S-H-) were Ki-67 index (P = 0.007) and the distribution pattern of CD8+ IETCs (P = 0.049). CD4 IETC counts were generally low, with no significant difference between all groups. The few S-H+ cases seen most likely represented false-negative serology, because the assessed parameters of this group and S+H+ cases were indistinguishable.     

Chronic exposure to cold stress alters electrophysiological properties of locus coeruleus neurons recorded in vitro.

Chronic stress exposure can alter central noradrenergic function. Previously, we reported that in chronically cold-exposed rats the release of norepinephrine and electrophysiological activation of locus coeruleus (LC) neurons is enhanced in response to multiple excitatory stimuli without alterations in basal activity. In the present studies, we used in vitro intracellular recording techniques to explore the effect of chronic cold exposure on the basal and evoked electrophysiological properties of LC neurons in horizontal slices of the rat brainstem. Consistent with our findings from in vivo experiments, chronic cold exposure did not affect basal firing rate. Furthermore, gross morphology of LC neurons and spike waveform characteristics were similar in slices from control and previously cold-exposed rats. However, excitability in response to intracellular current injection and input resistance were larger in slices from previously cold-exposed rats. In addition, the accommodation of spike firing in response to sustained current injection was smaller and the period of postactivation inhibition appeared to be less in LC neurons from cold-exposed rats. These data demonstrate that the stress-evoked sensitization of LC neurons observed in vivo is at least in part maintained in the slice preparation and suggest that alterations in electrophysiological properties of LC neurons contribute to the chronic stress-induced sensitization of central noradrenergic function observed in vivo. Furthermore, the present data suggest that an alteration in autoinhibitory control of LC activity is involved in the chronic stress-induced alterations. The enhanced functional capacity of LC neurons following cold exposure of rats may represent a unique model to study the mechanisms underlying the alterations in central noradrenergic function observed in humans afflicted with mood and anxiety disorders.     

The results of microneurosurgery of the inferior alveolar and lingual nerve.

PURPOSE: The goal was to evaluate the experience of one surgical unit during a 5-year period in the evaluation and management of patients with injuries of the inferior alveolar and lingual nerve with particular reference to indications for and results of microneurosurgery. PATIENTS AND METHODS: This study includes all patients referred with a diagnosis of injury to the inferior alveolar or lingual nerve during 5-year period from January 1, 1994, to January 1, 1999. All patients were evaluated with Frey's hairs for touch and direction sense, 2-point discrimination, and hot and cold water and Minnesota thermal discs for temperature sensation. Patients who fulfilled certain specified criteria were offered microneurosurgery, and the results were evaluated for those who underwent microneurosurgery. RESULTS: The study consisted of 880 consecutive patients; 96 were thought to fulfill the criteria for microneurosurgery. Of these, 51 underwent microneurosurgical exploration and repair. In 5 patients, no injury could be detected at surgery, and no corrective surgery was performed other than decompression. In 26 patients, excision and direct anastomosis were performed, and in an additional 20 patients, nerve gap reconstruction was performed. In 16 of these 20 patients, reconstruction was performed with an autogenous vein graft, and in 2 patients, a Gore-Tex tube graft (W.L. Gore & Associates, Inc, Flagstaff, AZ) was used to bridge the nerve gap. In 2 patients, an autogenous nerve was used. Thirty-four of the repairs were made on the lingual nerve, and 17 were made on the inferior alveolar nerve. With the use of established criteria, 10 patients were considered to have had a good improvement in sensation, 18 patients were considered to have had some improvement in sensation, and 22 patients were considered to have had no improvement in sensation; 1 patient reported an increase in dysesthesia after surgery. The semiobjective assessment of patients did not always correspond with the patients' subjective evaluation. CONCLUSION: In a relatively small study in selected cases, microneurosurgery can provide a reasonable result in improving sensation in the inferior alveolar and lingual nerve. More than 50% of patients experienced some improvement in sensation, and dysesthesia did not develop after surgery in any patient who did not have it before surgery.     

Clinical significance of SNAP somnography test acoustic recording.

OBJECTIVE: To examine the clinical significance of acoustic data recorded by the SNAP home polysomnography system (SNAP Laboratories, Glenview, IL). STUDY DESIGN AND SETTING: Retrospective analysis of SNAP data from 59 patients undergoing evaluation for sleep apnea at the University of Nebraska Medical Center and an associated private practice in Omaha, NE. RESULTS: Snoring did not correlate with anthropometric variables such as body mass index and neck circumference. Statistical analysis showed no correlation between respiratory disturbance index and the maximum or average loudness of snoring. Average loudness was predictive of the presence of sleep apnea. Spectral analysis of snoring sonography found that the proportion of snoring events associated with a palatal source correlated strongly with the loudness of snoring. CONCLUSION: These data suggest that analysis of snoring has limited utility in the evaluation of the patient with sleep apnea but may be able to select patients who would benefit from palatal procedures to reduce snoring.     

Medium term outcome for infant repair in tetralogy of Fallot: indicators for timing of surgery

Objective: To assess the impact of early corrective surgery on the short and medium term outcome in tetralogy of Fallot (TOF). Materials and methods: All patients under 12 months of age undergoing correction of isolated TOF between February 1997 and July 2003 were reviewed retrospectively. Outcome data for mortality, post-operative care management, major morbidity and clinical follow-up were analysed. Results: Fifty-two operations were performed. The mean age at surgery was 5 months (range 1–12) of whom 16 (30.8%) were less than 3 months old, including 2 neonates, 22 (42.3%) were 3–6 months old and 14 (26.9%) were 7–12 months old. There was 1 (1.9%) early death caused by a cerebro-vascular accident and 1 (1.9%) late death secondary to acute infective endocarditis. There were no differences in post-operative morbidities attributable to age. Patients under 3 months old required greater duration of post-operative ventilation, ITU stay and in-hospital stay. At a mean follow-up of 4.0 years (range 1.5–8.0), 33 (63.5%) patients had well-tolerated pulmonary regurgitation (PR) and 3 (5.8%) patients required re-operation for right ventricular outflow tract obstruction (RVOTO). All patients had right bundle-branch-block but with QRS < 150 ms. Conclusion: Early definitive repair of TOF can be performed safely on patients under 6 months old. Age at surgery does not appear to affect the medium term haemodynamic outcome. However, early surgery does escalate the need for ICU care. This data suggests repair in asymptomatic patients be delayed until 3–6 months of age.     

Physical and Sexual Abuse and their Relation to Psychiatric Disorder and Suicidal Behavior among Adolescents who are Psychiatrically Hospitalized

Adolescents who were psychiatrically hospitalized ( N = 105) were classified as sexually abused, physically abused, both sexually and physically abused, or not abused, and studied to determine the prevalence of suicidal behavior and psychiatric disorders. Self-reports of hopelessness, depression, coping, and self-concept were also examined. No difference in suicidal behavior or psychiatric disorder, based on abuse history, was found, with one exception. Adolescents who were sexually abused, particularly those who experienced the most severe sexual abuse, used negative coping strategies more often than those not sexually abused. Findings suggest that symptomatology of adolescents who are psychiatrically hospitalized does not differ markedly based on history of abuse.     

Proteolytic Processing Mechanisms in the Biosynthesis of Neuroendocrine Peptides: The Subtilisin-like Proprotein Convertases

The recent discovery of a novel family of precursor processing endoproteases has greatly accelerated progress in understanding the complex mechanisms underlying the maturation of prohormones, neuropeptides, and many other precursor-derived proteins. At least six members of this family have been found thus far in mammalian species, several having alternatively spliced isoforms, and related enzymes have been identified in many invertebrates, including molluscs, insects, nematodes, and coelenterates. The proprotein convertases are all dependent on calcium for activity and all possess highly conserved subtilisin-like domains with the characteristic catalytic triad of this serine protease (ordered Asp, His, and Ser along the polypeptide chain). Two members of this family, PC2(SPC2) and PC1/PC3(SPC3), appear to play a preeminent role in neuroendocrine precursor processing. Both convertases are expressed only in the brain and in the extended neuroendocrine system, while another important family member—furin/PACE (SPC1)—is expressed more ubiquitously, in almost all tissues, and at high levels in liver. SPC2 and SPC3 exhibit acidic pH optima and other properties which enhance their activity in the acidic, calcium-enriched environment of the dense-core secretory granules of the regulated pathway in neuroendocrine cells, while furin has a neutral pH optimum and is localized predominantly to the trans Golgi network where it is retained by a C-terminal transmembrane domain. Furin processes a wide variety of precursors in the constitutive pathway, such as those of growth factors, receptors, coagulation factors, and viral glycoproteins. Recent findings on the processing of proopiomelanocortin, proinsulin, proglucagon, and several other neuroendocrine precursors by SPC2 and SPC3 are discussed, along with information on the structure, properties, evolution, developmental expression, and regulation or the convertases. An inherited defect in the fat/fat mouse which affects the processing of proinsulin, and probably also many other prohormones, due to a point mutation in carboxypeptidase E has recently been identified and has begun to provide new insights into the functional integration of the individual processing steps.