Oxidative stress in blood in Alzheimer's disease and mild cognitive impairment: a meta-analysis.

Abnormal oxidative stress is an established feature of Alzheimer's disease, but clinical trials aiming to reduce oxidative stress have not yet proven an effective therapy for dementia patients. The purpose of this review is to systematically analyze available data describing markers of oxidative stress and antioxidants in blood from subjects with Alzheimer's disease or those with mild cognitive impairment to highlight potential interactions between peripheral redox changes and central nervous system pathology and contribute to the design of future clinical study. PubMed, SCOPUS and Web of Science were systematically queried to collect studies which have evaluated markers of oxidative stress, levels of antioxidants, copper, transferrin and ceruloplasmin levels in blood from subjects with Alzheimer's disease and matched controls. After application of quality measures, results were aggregated in a random effects analysis. We found that markers of lipid peroxidation are elevated in blood in Alzheimer's disease and in mild cognitive impairment, copper metabolism is dysregulated and total antioxidant capacity is decreased. While surprisingly none of the major antioxidative enzymes are significantly decreased, non-enzymatic antioxidants in blood (particularly uric acid, vitamins A, E and C, α- and ß-carotene) are significantly decreased. There is significant oxidative damage in peripheral blood early in the process of neurodegeneration. We propose that clinical studies assessing cognitive outcomes after antioxidant therapy tailor interventions to individual patients' deficiencies and confirm an improvement in an appropriate serological marker of oxidative stress. This strategy may be most effectively applied in a clinical trial of primary prevention.

Bulk isolation in nonaqueous media of nuclei from lyophilized cells.

Intact lyophilized nuclei are obtainable from a variety of tissues, either in situ or in culture, by freezing at -156 degrees C, drying at -25 degrees C, and mechanical disassociation in glycerol at 2 degrees C. Centrifugal separation of nuclei is accomplished in an 85 : 15 by volume mixture of glycerol and 3-chloro-1,2 propanediol at 2 degrees C. The method gives homogeneous nuclear preparations in high yield with preservation of labile and water-soluble constituents.

In vitro plasminogen activator activity in human brain tumors.

Cell cultures were prepared from nine human brain tumors. Fibrin plate assays showed plasminogen-dependent fibrinolytic activity in lysates and in material released by these neoplastic cells but not in those from normal adult human white matter. Antibodies against human urokinase caused catalytic inhibition of the urokinase and of the plasminogen activator from WI-38 cells, simian virus 40-transformed WI-38 cells, human prostatic cells, and human ovarian carcinoma cells. However, the anti-urokinase immunoglobulin G did not inhibit the plasminogen activator activity of any of the human brain tumor preparations. These studies indicate that the plasminogen activator produced by human brain tumor cells is antigenically different from the plasminogen activator of other human normal and neoplastic cells.

Left stellectomy in the long QT syndrome.

Recent investigations have reaffirmed the role of autonomic innervation of the heart in the genesis of certain cardiac arrhythmias. The long QT syndrome (LQTS) has been described for years, but only recently has evidence of its link to autonomic imbalance been established. A case of LQTS is presented with intraoperative evidence at the time of left stellectomy of life-threatening arrhythmias triggered by stimulation of this neural body. Removal of the left stellate ganglion normalized the electrocardiographic (ECG) abnormalities and has rendered the patient asymptomatic since surgery. Left stellectomy may become definitive therapy for selected patients with the LQTS.

A comparative study of apoptosis and cell proliferation in infantile and adult fibrosarcomas.

The infantile fibrosarcoma, a rare tumor phenotypically similar to the adult fibrosarcoma, frequently has a benign course marked by spontaneous regression. Because biologic mechanisms responsible for this regression remain unexplained, an investigation of the role of apoptotic cell death is warranted. The rate of apoptotic cell death has been compared in five cases each of infantile and adult fibrosarcoma by quantitative estimation of in situ DNA double strand breaks. Although positively stained apoptotic cells are evident in all 10 cases, the apoptotic index is significantly higher in infantile cases (mean 6.6% +/- 0.80) compared to adult cases (mean 0.5% +/- 0.08). The proliferative (MIB-1) index of each specimen has been calculated by immunostaining for cell cycle phase-dependent Ki-67 antigen with MIB-1 antibody. Infantile cases have a significantly lower proliferative (MIB-1) index (mean 0.4 +/- 0.15) than adult counterparts (mean 15.9 +/- 3.76). The relatively benign course of the infantile fibrosarcoma may be due to two factors--a significantly lower proliferative (MIB-1) index coupled with enhanced apoptosis.

Facilitated vascular anastomoses: the one-shot device.

BACKGROUND: A mechanical system for facilitating vascular anastomosis (end-to-side, end-to-end) is described that enables the rapid construction of nonpenetrated, compliant junctions. The instrument (United States Surgical One-Shot system) simultaneously applies either 10 or 12 nonpenetrating, arcuate-legged titanium clips to everted vessel or prosthetic conduit edges. METHODS AND RESULTS: The instrument has been tested in animals (jugular and femoral vein jump grafts in carotid and femoral arteries, interpositional grafts, 20 pigs) and human cadaveric constructs (saphenous veins to left anterior descending coronary arteries, 20 cases, 5 brachiocephalic access fistulas) as end-to-side constructs. Clipped constructs have equivalent or superior physical properties to control sutured constructs (6-0 polypropylene) as gauged by burst and tensile strength. All studies were performed under Food and Drug Administration Good Laboratory Practice standards, and the device has been approved for marketing by the Food and Drug Administration. CONCLUSIONS: The device enables rapid and reproducible vascular anastomotic constructs with vessels as small as 1.8 mm outer diameter. The constructs are flanged, interrupted, and nonpenetrated.

Sutureless vasovasostomy: new technique using experimental microclip in rat model.

Standard microscopic suture vasovasostomy represents a challenge to many urologists. It is technically demanding, and requires two to five hours of operative time. In an attempt to decrease the technical demand and the time requirement, we report the use of a microvascular anastomotic clip and compare this microclip to a standard eight-suture nonstented technique and a six-suture stented technique using a hollow, absorbable 0.5-mm polyglycolic acid stent. The control group with suture required an average of 38.5 minutes per anastomosis for the nonstented group and twenty-two minutes for the stented group. The clip group required 7.6 minutes for the unstented vasovasostomy and 6.5 minutes for the stented vasovasostomy. We obtained a 91 percent patency rate for the stented clip group and 100 percent patency for the unstented clip group. In a rat vasovasostomy, the operative time as well as the inherent technical demand were significantly reduced.

Juvenile nasopharyngeal angiofibroma: management of intracranial extension.

Juvenile nasopharyngeal angiofibroma (JNA) is a histologically benign, locally invasive tumor of the nasopharynx that is found primarily in the pubescent male. While most authors recommend surgical excision for smaller, localized extracranial tumors, opinion varies on the management of more aggressive tumors with intracranial extension. The authors present their experience over the past 15 years with 15 cases of JNA with intracranial extension, and formulate a plan of management. A combined otolaryngologic/neurosurgical approach is recommended in order to assess the extent of the tumor and to isolate feeding vessels. Lateral extension into the middle cranial fossae should be resected in continuity with the nasopharyngeal component, which is approached from below in a separate operative field. Medial extensions are transected, verified angiographically three months after surgery, and irradiated. The results of therapy are presented, and a case of dural penetration by JNA is described.

A new concept for anastomosis of the fallopian tube: tissue reconstruction with nonpenetrating, arcuate, legged clips in the rat model.

OBJECTIVE: To evaluate the titanium Kirsch-Zhu microclip microsurgical reanastomoses of the fallopian tubes. DESIGN: Compare the reanastomoses of the rat uterine horn between Kirsch-Zhu clips (Cushman Engineering, Albuquerque, NM) (group A) and conventional suture microsurgical techniques (group B). SETTING: Microsurgery Research Laboratory, Loma Linda University Medical Center, Loma Linda, California. PATIENTS, PARTICIPANTS: Fifteen SD rats Harlan (Harlan Sprague-Dawley Corp., Indianapolis, IN) were done in groups A and B and six in control group (C). MAIN OUTCOME MEASURE: Pregnancy rate, litter size, tissue of procedure, and histologic results. RESULTS: The clip technique was shorter in procedure time and resulted in equal fertility rate and litter size. Histologically, there were less granulomatous formation and histiocytic inflammation, but muscularis thinning and fibrosis were noted with the clip. CONCLUSIONS: The Kirsch-Zhu clip has potential for application to human fallopian tube reanastomoses.

The fine structural localization of S-100 protein in rodent cerebellum.

This report describes the first fine structural locations of S-100 protein in the hamster cerebellum. Innovations in tissue fixation as well as tracer preparation enable localization of S-100 protein to several critical cellular and subcellular sites. Certain neuronal elements, Purkinje cells, contain S-100 protein in both cytoplasm and nucleus. Specific membrane structures including plasma membranes and the nuclear membranes of Purkinje cells are strikingly positive. Localization of S-100 protein to the pericapillary astrocytic endfeet as well as regions of the synapse are of particular biological interest. The clear nuclear localization of the molecule suggests a role in the genetic expression of the developing mammalian brain.

Biodistribution and radioimmunopharmacokinetics of 131I-Ama monoclonal antibody in atherosclerotic rabbits.

Monoclonal antibodies have been raised against Ama isolated from human and experimental atherosclerotic plaque. 131I-Ama-MoAb in the whole antibody form was injected into normal NZW rabbits and Watanabe hyperlipidemic rabbits. Biodistribution studies showed that atheromatous aortas had a significantly higher (5-7X) uptake of 131I-Ama-MoAb than that of normal aortas. However, 131I-Ama-MoAb was cleared very slowly from atherosclerotic rabbits. As a result, atheromas could not be identified by imaging because of the low target to non-target ratios.

Dural closure with nonpenetrating clips prevents meningoneural adhesions: an experimental study in dogs.

OBJECTIVE: Meningospinal and cranial dural adhesions were compared in a canine model, after duraplasty using nonpenetrating clips or penetrating needles and sutures. METHODS: Fourteen dogs underwent bilateral craniotomies and duraplasties, with implantation of dural prostheses (DuraGuard; Biovascular Corp., Minneapolis, MN), using either 6-0 silk sutures or titanium clips (DuraClose; Surgical Dynamics, Norwalk, CT). Fourteen other dogs underwent L3-L4 laminectomies; three longitudinal dural incisions were closed with 6-0 silk sutures, 6-0 polyglactin 910 (Vicryl) sutures, or clips. Groups of eight dogs (four cranially treated and four spinally treated) were killed 6, 12, 24, and 52 weeks after surgery, and specimens were collected for study after perfusion and fixation (two cranial and two spinal dural reconstructions at 52 wk). Evaluations included assessment of the appearance of approximated dural margins and responses to clips, sutures, and dural prostheses (inflammation, foreign body reaction, fibrosis, and severity of meningospinal/meningocerebral adhesions). Data were evaluated using the Wilcoxon signed-rank and McNemar tests. RESULTS: Duraplasties with clips displayed significantly less extensive acute and chronic inflammation, foreign body reaction, and meningoneural adhesions than did repairs with needles and sutures. CONCLUSION: This report is the first long-term experimental study comparing two fundamentally different methods for dural repair in a relevant animal model.

Follow-up analysis of ventriculoperitoneal and ventriculoatrial shunts for hydrocephalus.

The authors report an analysis of 300 patients in whom primary treatment for hydrocephalus was either a ventriculoperitoneal (VP) or ventriculoatrial (VA) shunt. Although differences in primary and total revision rates between placements were not statistically significant, the VA shunt failures carried a higher morbidity than the VP placements.

Retrospective analysis of 22 patients with chronic pain treated by peripheral nerve stimulation.

Twenty-two patients with chronic pain, chiefly from posttraumatic neuropathy, were treated by implanted peripheral nerve stimulators located proximal to the pain. Thirteen of these (62%) have experienced pain control for an average of 25 months. The experience of the surgeon is thought to be a major factor contributing to the successful results. There are theoretical and practical advantages to electrical stimulation and proximal portions of the peripheral nervous system. The surgical technique for implantation is described and the necessity for reoperation in some patients is explained.

Atlanto-axial dislocation in acute rheumatic fever. Case report.

A 10-year-old boy had a sore throat, followed in 4 weeks by acute rheumatic fever and in 6 weeks by atlanto-axial dislocation. Reduction of the dislocation by means of a halo vest relieved his pain, but the cervical spine remained unstable after 3 months of immobilization and required an occiput-C1-2 fusion and rib graft to stabilize the atlanto-axial joint. This is the eighth reported case of atlanto-axial dislocation associated with acute rheumatic fever. The features of previous cases are summarized and the clinical aspects, mechanisms, diagnosis, and treatment of atlanto-axial dislocation are reviewed.

Diagnosis and treatment of abscess of the central ganglia.

The authors present four cases of abscess of the thalamus and basal ganglia and review an additional 10 cases from the literature. These abscesses appear to be metastatic and are usually associated with a cardiac septal defect or a preceding intrathoracic infection. Fever, elevated white blood count, and/or meningismus, in combination with angiography demonstrating an avascular mass, help distinguish abscess from tumor in this location. The authors advocate aspiration rather than excision.

Reoperation after lumbar intervertebral disc surgery.

This retrospective study includes 53 patients who underwent reoperation after failure of lumbar disc surgery to relieve pain. All patients had leg pain before reoperation, which was successful in 28% of cases. Most clinical features, such as persistence or mode of recurrence of pain, radicular quality of pain, positive straight-leg raising, and myelographic root sleeve defects, were not helpful in predicting successful and unsuccessful reoperations. However, a significantly larger percentage of women than men had successful reoperations. Patients who had past or pending compensation claims, who had sensory loss involving more than one dermatome, or who failed to have myelographic dural sac indentations resembling those caused by a herniated disc did poorly with reoperation. A very convincing myelographic defect appears to be needed to justify reoperation at a previously unoperated location. Excision of scar alone or dorsal rhizotomy was of no avail in these cases.

Testolactone, sulindac, warfarin, and vitamin K1 for unresectable desmoid tumors.

Ten patients with large inoperable desmoid tumors in various body locations were treated with testolactone. Four tumors (40%) responded with major regressions, i.e., more than 50% reduction in volume. Eight patients received nonsteroid anti-inflammatory drugs (indomethacin, sulindac, or sulindac with warfarin and vitamin K1 [Mephyton]) for periods of 2 to 91 months. There was one major regression, one partial regression, and three instances of tumor growth arrest over periods up to 8 years. Seven patients were treated with nonsteroid anti-inflammatory drugs concurrent with or after testolactone or tamoxifen. There were five major regressions and one partial regression with extensive central necrosis of an enormous intra-abdominal tumor. The last patient has been treated for only 12 months, with no change in tumor volume. It appears that estrogens function as growth factors for desmoid tumors, and that minimization of these effects inhibits tumor growth in some, but not all, cases. In those instances where antiestrogens were not effective as single agents, the tumors usually responded to subsequent nonsteroid anti-inflammatory drug therapy. Withdrawal of estrogen may be followed by inhibition of transcription of genes that support tumor cell proliferation, and sulindac and indomethacin may augment these effects by inhibiting prostaglandin and cyclic AMP synthesis and the activity of protein kinase C. Warfarin may function as a protonophore to acidify the cytoplasm and prevent the alkalinization that is necessary to initiate DNA synthesis and cell cycle progression, again an impairment of the transcription process.

A new method for microvascular anastomosis: report of experimental and clinical research.

Principles of microvascular anastomotic surgery are uncertain in contrast to the standardized suture methods for the repair of large arteries. Complications of early thromboses or late stricture at the microvascular anastomotic line can be related to the inherent biologic response of these delicate tissues to penetrating needle and suture. A new method for microvascular reconstruction based on the principle of flanged, nonpenetrated, intimal approximation by an arcuate-legged clip has proven biologically and technically superior to the penetrating microsuture. These conclusions are based on extensive testing in multiple surgical laboratories of the following parameters: long- and short-term patency, morphology of wound repair, and burst and tensile strength. Details of the new surgical system and experimental studies are described.

Monitoring of visual function during parasellar surgery.

Damage to the visual system is an unfortunate complication of surgery in the area of the optic chiasm. It is now possible tomonitor the functional status of the visual system intreoperatively at regulat intervals. This is accomplished by recording the Visual Evoked Response to flashes of light from light-emitting-eiodes. These diodes are embedded in a special plastic shell which inserts under the eye lids of each eye. Since the light comes from the diodes in the plastic shell, there is no need to disturb the surgical procedure when a test run is desired. A record is obtained by averaging 100 three-per-second flashes.