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.     

Substantial inhibition of neo-intimal response to balloon injury in the rat carotid artery using a combination of antibodies to platelet-derived growth factor-BB and basic fibroblast growth factor

Thirty percent of patients undergoing percutaneous transluminal coronary angioplasty develop recurrent disease within a year. This is usually due to the rapid accumulation of intimal smooth muscle cells and extracellular matrix, which causes luminal narrowing, and is probably orchestrated by several mitogenic and chemotactic factors, of which platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF) appear to be particularly important. We have investigated the effects of administering a combination of neutralizing antibodies directed against PDGF-BB and bFGF on neo-intima development following balloon catheter injury in the rat carotid artery. Purified sheep anti-PDGF-BB and anti-bFGF immunoglobulins (IgGs) were administered singly and in combination prior to mechanical injury and daily until sacrifice, 8 days later. Plasma titres of exogenous anti-PDGF-BB and anti-bFGF were maintained at levels 10–20-fold higher than those required to neutralise the mitogenic and chemotactic effects of 20 ng/ml of PDGF-BB, or 10 ng/ml bFGF in vitro. Used singly, anti-PDGF IgG treatment was associated with a 47% reduction in intimal thickness and a 59% reduction in intimal:medial area ratio; anti-bFGF IgG administration caused a 53% reduction in intimal thickness, and a 50% reduction in intimal:medial area ratio. Treatment with a combination of these antibodies resulted in a 83.8% reduction in intimal thickness (P<0.05), and a 91% reduction in intimal:medial area ratio (P<0.01). The latter treatment was also associated with a significantly higher intimal cell density (14.2±1.6×10³ nuclei/mm²) compared to animals receiving non-immune IgG (7.8±0.8×10³ nuclei/mm²; P<0.025), although intimal and medial cell proliferation indices were not significantly different between the groups (P>0.05). Our results suggest that in this particular model, PDGF-BB and bFGF are the major factors controlling neointimal hyperplasia, and that these growth factors are operating principally via an effect on smooth muscle cell migration and extracellular matrix protein accumulation.     

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.     

Omega-3 fatty acids in major depressive disorder. A preliminary double-blind, placebo-controlled trial.

Patients with depression have been extensively reported to be associated with the abnormality of omega-3 polyunsaturated fatty acids (PUFAs), including significantly low eicosapentaenoic acid and docosahexaenoic acid in cell tissue contents (red blood cell membrane, plasma, etc.) and dietary intake. However, more evidence is needed to support its relation. In this study, we conducted an 8-week, double-blind, placebo-controlled trial, comparing omega-3 PUFAs (6.6 g/day) [corrected] with placebo, on the top of the usual treatment, in 28 patients with major depressive disorder. Patients in the omega-3 PUFA group had a significantly decreased score on the 21-item Hamilton Rating Scale for Depression than those in the placebo group (P < 0.001). From the preliminary findings in this study, omega-3 PUFAs could improve the short-term course of illness and were well tolerated in patients with major depressive disorder.