De-novo expression of vascular ecto-5′-nucleotidase and down-regulation of glomerular ecto-ATPase in experimental chronic renal transplant failure

Ischemic injury plays an important role in chronic renal transplant failure (CRTF). Down-regulation of ecto-adenosine triphosphatase (ATPase) in combination with up-regulation of ecto-5'-nucleotidase is a hallmark of ischemic injury. We studied the expression of renal ecto-5'-nucleotidase and ecto-ATPase in experimental renal transplantation. Fisher 344-to-Lewis allografted rats were either treated with an angiotensin-converting enzyme inhibitor (ACEi) or left untreated. Lewis-to-Lewis syngrafted rats served as controls. Untreated allografted rats developed proteinuria, glomerulosclerosis, and mild intimal hyperplasia. ACEi completely prevented focal and segmental glomerulosclerosis (FGS) and proteinuria, but significantly enhanced intimal hyperplasia. Untreated allografted rats revealed marked vascular ecto-5'-nucleotidase activity, which increased with ACEi. Vascular ecto-5'-nucleotidase activity was absent in syngrafted animals. Ecto-5'-nucleotidase activity correlated well with intimal hyperplasia. Glomerular ecto-ATPase expression was significantly reduced in untreated allografted rats compared to syngrafted rats and correlated well with the extent of FGS. ACEi prevented reduction in glomerular ecto-ATPase. We found de-novo expression of ecto-5'-nucleotidase at sites of renal intimal hyperplasia. Glomerular ecto-ATPase expression was markedly reduced in allografted rats and was prevented by ACEi. These enzyme expression patterns suggest local ischemic damage in experimental CRTF.     

Revision endoscopic frontal sinus surgery with surgical navigation.

BACKGROUND: Revision surgery of the frontal sinus remains one of the most difficult operations for the endoscopic surgeon. Most agree that knowledge and recognition of its complex anatomy and sparing of frontal recess mucosa are keys to a successful operation. The use of surgical navigation systems may allow for more precise dissections and greater rates of frontal recess patency. METHODS: Retrospective review of all patients undergoing revision endoscopic frontal sinus surgery with surgical navigation was performed with a minimum 24-month follow-up. RESULTS: Sixty-seven patients underwent revision endoscopic frontal sinus surgery with surgical navigation. The average follow-up was 32 months. Fifty-eight (86.6%) had a patent frontal recess and significant subjective improvement in symptoms. No patient underwent external frontal sinus obliteration, and there were no major complications. CONCLUSIONS: Endoscopic techniques with surgical navigation are effective in revision frontal sinus cases. The dissection of remnant agger nasi, obstructing frontal and supraorbital cells are necessary to widen the anterior-posterior as well as the medial-lateral dimensions of the recess. Computer navigational systems appear to serve as a valuable adjunct in preoperative planning and safe intraoperative dissection.     

Novel heteroplasmic mtDNA mutation in a family with heterogeneous clinical presentations.

The protean manifestations of a novel maternally inherited point mutation of the mitochondrial genome are reported. The proband showed isolated, spastic paraparesis. A brother, who had suffered from a multisystem progressive disorder, ultimately died of cardiomyopathy. Another brother is healthy. The proband's mother showed truncal ataxia, dysarthria, severe hearing loss, mental regression, ptosis, ophthalmoparesis, distal cyclones, and diabetes mellitus. A muscle biopsy performed in the proband failed to show the morphological abnormalities typical of mitochondrial disorders; the activities of respiratory chain complexes were normal. However, complex I and IV activities were low in the muscle homogenate of the affected mother and brother. Sequence analysis of mtDNA showed a heteroplasmic mutation of the tRNA(Ile) gene (G4284A). The mutation load was approximately 55%, 80%, and 90% in the muscle mtDNA of the proband, his mother, and his affected brother, respectively. Mutation was undetected in the healthy brother, as well as in 100 control samples. Several cybrid clones containing homoplasmic mutant mtDNA from the proband showed significant reductions of complex IV activity and maximum oxygen consumption rate, compared with homoplasmic wild-type clones derived from the same subject.     

A preliminary study of serotonergic antidepressants in treatment of dysthymia

Rosenthal, Jesse et al. A Preliminary Study of Serotonergic Antidepressants in the Treatment of Dysthymia. Prog. Neuro-Psychopharmacol. & Biol. Psychiat. 1992, 16(6): 933–941.

1. 1. There is increasing evidence that antidepressants may alleviate symptoms of dysthymia, but few prior studies on selective serotonergic agents.

2. 2. Twenty patients meeting criteria for dysthymia, but not meeting criteria for major depression, received open label trials of a serotonergic antidepressant, either fluoxetine or trazodone.

3. 3. Seventeen (85%) completed three-month medication trials, and of these, twelve (70.6% of completers) responded to treatment. Seven (41.2% of completers) were still in remission on followup at five months.

4. 4. Both fluoxetine and trazodone were well tolerated in dysthymics, and showed similar short-term effectiveness in treating dysthymic symptoms.

Altered corticomotor representation in patients with Parkinson's disease.

In 6 patients with Parkinson's disease (PD) and 6 age-matched controls, transcranial magnetic stimulation was applied at 56 regions over the motor cortex and premotor cortex of each hemisphere, with the first dorsal interosseous (FDI) muscle of both hands activated at 15% maximum voluntary contraction during stimulation. For each site, motor evoked potential (MEP) landmarks were recovered, including MEP amplitude, MEP onset latency, and silent period duration. Scaled MEP amplitudes were used to construct individual cortical maps of the FDI muscles. The maps revealed an anterior displacement of the muscle representation in PD patients. This anterior shift over motor cortical areas may reflect increased contributions of corticocortical connections between motor cortex and premotor cortical areas, possibly enhanced by the visual feedback aspect of the task. These alterations may reflect adaptations to the impairments in striatocortical circuits in PD.     

Nationwide survey on the use of image-guided functional endoscopic sinus surgery.

OBJECTIVE: To evaluate impressions and usage of sinus surgery image-guided surgical (IGS) systems by ENT surgeons in the United States. STUDY DESIGN AND SETTING: A survey was mailed to selected practicing ENT physicians, investigating regional information, practice type, IGS usage patterns, perceived benefits and limitations, and usage of the 61795 surgery code. RESULTS: Seventy-three percent of respondents use IGS. Nonusers respond that it provides no benefit or is too expensive. Eighty percent of respondents replied that IGS may allow for increased safety in certain procedures. Most users attempt reimbursement with the 61795 code. CONCLUSION: IGS usage is increasing but appears to be perceived as expensive and nonbeneficial in certain situations. Most respondents, however, felt that IGS may lead to safer surgery in certain situations, including revision and frontal procedures. Several factors appear to limit routine use including ease of use, technical setup, code reimbursement, and initial purchase costs. SIGNIFICANCE: IGS use appears to be increasing. The most frequent users appear to agree with the previously issued AAO-HNS guidelines regarding appropriate indications. Expanded use may depend on ease of use, reimbursement, and affordability. EBM rating: D-5.     

Elevated threshold for intracortical inhibition in focal hand dystonia.

Differences between control and focal hand dystonia (FHD) subject groups in short interval intracortical inhibition (SICI) as determined by paired transcranial magnetic stimulation (TMS) can be difficult to demonstrate, due to interindividual differences. The purpose of this study was to compare two TMS methods for assessing SICI in 8 control and 7 FHD subjects. Electromyographic (EMG) data were recorded from the first dorsal interosseous (FDI) muscle of the dominant hands of the control subjects and affected hands of the FHD subjects. The first method used a conventional approach of setting conditioning stimulus intensity to 80% of rest threshold (RTh) and test stimulus intensity to 120% RTh. Three interstimulus intervals (ISIs) were used: 2 msec, 3 msec, and the ISI between 2 and 3 msec that produced optimal SICI. The second method was novel in that test stimulus intensity was set to 150% active threshold (ATh), and conditioning stimulus intensity was varied between 50% and 100% ATh. The latter was determined at the threshold for SICI and expressed as a ratio of ATh. There was no difference between the subject groups in the degree of SICI produced using the first method, at the three ISIs studied. However, using the second method, the SICI threshold:ATh ratio was found to be significantly higher for FHD subjects. This finding suggests that determining the SICI threshold:ATh ratio may be a more sensitive measure of intracortical inhibitory function than more conventional methods.     

Spatial low frequency pattern analysis in positron emission tomography: a study between normals and schizophrenics.

Using the two-dimensional Fourier transform and the brain's centroidal principal axis, a method is developed for the analysis of PET metabolic brain images without the use of predefined anatomic regions of interest. We applied the method to images from a group of 11 normal and 12 medicated schizophrenics tested under resting conditions and under a visual task. A cortical/subcortical spatial pattern was found to be significant in two directions; anterior/posterior and chiasmatic (left-anterior/right-posterior). The best individual clinical classification (Jackknife classification) occurred under visual task at two axial brain levels: at the basal ganglia with correct classification rates of 91% and 84%, while the cerebellum had rates of 82% and 92%. These high classification rates were obtained using only the four coefficients of the lowest spatial frequency. These results point to the generalized brain dysfunction of regional glucose metabolism in chronic medicated schizophrenics both at rest and at a visual image-tracking task.