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Biomedical subjects

M Belkin

Publications and source records attributed to M Belkin.

At least 19 recordsLinked to original sources

Identification of an interleukin 2-like substance as a factor cytotoxic to oligodendrocytes and associated with central nervous system regeneration.

Axons of the central nervous system in adult mammals do not regenerate spontaneously after injury, partly because of the presence of oligodendrocytes that inhibit axonal growth. This is not the case in lower vertebrates (e.g., in fish), where regeneration of the optic nerve does occur spontaneously and has been correlated with the presence of factors cytotoxic to oligodendrocytes. The present study provides evidence that the substance originating from the fish optic nerves, which is cytotoxic to oligodendrocytes, is an interleukin 2-like substance.

Animals

Horseradish peroxidase labeling of growth cones and axons beyond the site of injury in injured rabbit optic nerve axons growing in their own environment.

Spontaneous growth of injured axons in the mammalian central nervous system is limited. We have previously shown an apparently regenerative growth of injured optic axons in the adult rabbit, achieved by supplying them with soluble substances originating from growing axons, followed by low energy helium-neon laser irradiation. The growing unmyelinated and thinly myelinated axons were embedded in astrocytes, and some were in the process of remyelination by oligodendrocytes. They were shown to have originated from the retinal ganglion cells. The present study further supports evidence relating to the origin and nature of these axons. Light microscopic analysis of these axons labeled with anterogradely transported horseradish peroxidase revealed that many of these axons have varicosities and bear growth cone-like swellings in their tips. These axons traverse the lesion site and extend into the distal stump in a disorganized pattern.

Animals

A long-term follow-up of metallic intraocular foreign bodies, employing diagnostic x-ray spectrometry.

We describe 10 eyes harboring metallic intraocular foreign bodies (IOFBs) for 9 to 46 years that had undergone diagnostic x-ray spectrometry to measure metal dissolution 9 years before this study. Findings from the present clinical and laboratory examinations, including perimetry, electroretinography, electrooculography, and diagnostic x-ray spectrometry examinations are reported. Deterioration in visual acuity consequent to metal dissolution of the IOFB was found in only one eye. Visual fields and electrophysiologic performances deteriorated in two other eyes for reasons that were probably unrelated to IOFB dissolution. Visual functions remained stable during the follow-up period in seven eyes, although excess copper levels were demonstrated in one of them. Eight of 10 eyes retained visual acuity of 6/24 or better. Diagnostic x-ray spectrometry confirmed siderosis in one patient and ruled out metallosis in the two patients with deteriorated vision for reasons that were unrelated to metallosis. The favorable outcome of this series of patients may influence one to consider a more conservative approach in the decision to remove IOFBs. A careful, life-long follow-up might be considered with periodic electroretinographic and diagnostic x-ray spectrometry examinations; the IOFB should be promptly removed if and when metallosis with damage to visual functions is demonstrated.

Adult

The effect of suprarenal cross-clamping on abdominal aortic aneurysm repair.

Two hundred five patients who underwent elective abdominal aortic aneurysm repair were divided into two groups: those who underwent infrarenal cross-clamping alone (n = 166) and those who underwent suprarenal cross-clamping alone or combined with infrarenal cross-clamping (n = 39). Mortality was comparable between groups (1.2% for infrarenal cross-clamping vs 2.6% for suprarenal cross-clamping). Transient renal insufficiency was more frequent in the suprarenal group than in the infrarenal group (28% vs 10%), but dialysis rates (3% for suprarenal vs 2% for infrarenal) were similar. Cardiac morbidity was comparable between groups as well. Operating room data reflected the technical challenge of complex aneurysm repairs. The retroperitoneal approach was the preferred exposure in the suprarenal group since better access to the suprarenal aorta may be achieved with this technique. While abdominal aortic aneurysm repairs requiring suprarenal cross-clamping remain a technical challenge, the risks are not formidable and suprarenal cross-clamping should be considered when confronted with difficult periaortic dissection.

Academic Medical Centers

Immediate retinal adhesion by CO2 laser irradiation using a fiberoptic intraocular probe.

Using an experimental fiberoptically guided CO2 laser system, we produced lesions on fresh bovine retinas. These lesions were shown to achieve immediate measurable chorioretinal adhesion. This model provides preliminary data on the use of a fiberoptic CO2 laser probe to produce chorioretinal lesions and possible future use in intraocular surgery for retinal detachment. The advantages of using CO2 laser energy are minimal damage surrounding desired lesion and its versatility as a coagulator and cutter. With modifications, CO2 endolaser may have a role in intraocular surgery.

Animals

Clinical and hemodynamic results of bypass to isolated tibial artery segments for ischemic ulceration of the foot.

Patients with ischemic ulceration of the foot and no continuous tibial or inframalleolar vessels acceptable for bypass are often treated with primary amputation. We have performed autogenous vein bypass to isolated tibial artery segments (ITAS) in nine patients with ischemic foot ulcers and no other outflow options. We reviewed the clinical and hemodynamic results of these bypasses to assess the efficacy of this approach. Hemodynamic comparisons of these ITAS bypasses were made to a concurrent series of 26 bypasses to intact tibial arteries and 24 inframalleolar artery bypasses assessed during routine follow-up. Eight of the bypasses originated from the above-knee popliteal artery and one from the profunda femoris artery. Recipient vessels were the anterior tibial (seven), peroneal (one), and posterior tibial (one) arteries. Although mean ankle brachial indices (ABI) increased significantly from 0.26 +/- 0.06 preoperatively to 0.75 +/- 0.04 postoperatively (p = 0.0015), ITAS bypass patients had lower mean postoperative ABIs than patients with bypasses to intact tibial (ABI = 0.98 +/- 0.03, p = 0.0001) or pedal arteries (ABI = 1.02 +/- 0.04, p = 0.0005). Similarly, duplex scan-derived peak systolic flow velocities of the ITAS bypasses (mean: 52.9 +/- 5.8 cm/sec) were lower than those of intact tibial artery bypasses (mean: 80.1 +/- 6.1 cm/sec, p = 0.02) but did not differ from those of pedal bypasses (mean: 59.5 +/- 3.5 cm/sec, p = 0.34). No ITAS bypass grafts have failed during a mean follow-up of 12.3 +/- 2.7 months. Although wound healing was prolonged (mean: 3.1 +/- 0.6 months), the wounds of eight of nine patients eventually healed, with three patients requiring minor amputations (one digital amputation and two transmetatarsal amputations). Although the hemodynamic results of ITAS bypass are inferior to those of more conventional bypasses, the early patency rates and successful healing of ischemic wounds confirm that it is a valid alternative in the threatened limb with no other outflow options.

Aged

The variation in vein graft flow velocity with luminal diameter and outflow level.

Duplex scanning has recently been used to monitor the patency of infrainguinal vein grafts. Empirically derived criteria that have been used for identifying the failing graft have never accounted for the effect of vein graft diameter or varying outflow resistance, despite the fact that they are major determinants of flow. We prospectively examined the variation in graft peak systolic flow velocity with graft diameter and outflow level in a consecutive series of 68 patients with 72 normally functioning vein grafts returning for routine follow-up. Images were obtained of vein grafts with a duplex scanner throughout their lengths, and the distal peak systolic flow velocity and intraluminal diameters were recorded. There were 15 popliteal, 26 tibial, and 21 inframalleolar grafts. The mean ankle-brachial index of inframalleolar grafts was 1.01 +/- 0.04 and did not differ significantly from tibial (0.96 +/- 0.03) or popliteal (0.93 +/- 0.06) grafts (p = 0.32). Grafts to the three outflow levels differed significantly in diameter, with inframalleolar grafts measuring 3.95 +/- 0.17 mm, tibial grafts 4.78 +/- 0.21 mm, and popliteal grafts 5.65 +/- 0.38 mm (p = 0.0001). In a similar manner inframalleolar grafts had significantly lower peak systolic flow velocities (59.1 +/- 3.4 cm/sec) than tibial (77.2 +/- 5.6 cm/sec) or popliteal (71.0 +/- 7.6 cm/sec) grafts (p = 0.04). Inframalleolar grafts did not demonstrate a significant correlation (r = -0.21, p = 0.29) between peak systolic flow velocity and graft diameter. Conversely, both tibial (r = -0.49, p = 0.005) and popliteal (r = -0.73, p = 0.002) grafts demonstrated significant inverse correlations.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Late stroke after carotid endarterectomy: the role of recurrent stenosis.

Perioperative stroke after carotid endarterectomy has been well studied, although little information is available regarding later strokes. We determined the etiology of late stroke after carotid endarterectomy by examining the records of those patients in our carotid registry who had a stroke more than 30 days after surgery. Thirty-five (5.1%) of the 688 patients in our registry had a stroke more than 30 days after surgery (mean follow-up, 59.3 months; standard error, 1.8 months; range, 1 to 292 months). The cause of late stroke was established by input from consulting neurologists, CT scanning of the head, magnetic resonance imaging results, angiograms, noninvasive studies, and postmortem examinations. Eight of the 11 strokes of unknown origin were massive fatal events for which no further evaluation was undertaken. Restenosis or occlusion accounted for fewer strokes (3 of 20, 15%) in the 1- to 36-month postoperative interval than in the greater than 36-month interval (8 of 15, 53.7%) (p less than 0.02 by Fisher's Exact Test). These data support the hypothesis that the early pseudointimal hyperplastic lesion is less likely to result in stroke than is later recurrent stenosis, which is usually related to atherosclerosis.

Arteriosclerosis

Routine postendarterectomy duplex surveillance: does it prevent late stroke?

Our recent finding that less than 50% of late postendarterectomy strokes are related to recurrent carotid stenosis led us to question the utility of routine postendarterectomy duplex surveillance (RpCEADS) in the prevention of late stroke. To evaluate our RpCEADS program, we reviewed our postoperative duplex studies and correlated their results with clinical data. A total of 1053 postendarterectomy scans was carried out on 348 carotid arteries (258 patients) (3.0 +/- 0.1 studies/artery) during an average follow-up of 52.6 (+/- 2.3) months. Less than 50% of recurrent carotid stenosis was documented throughout follow-up in 292 (83.9%) of 348 arteries. Recurrent carotid stenosis of greater than 50% or occlusion of either the common or internal carotid artery was noted in the remaining 56 arteries (16.1%). Of the 56 duplex-detected recurrent stenoses, only two (3.6%) resulted directly in an unheralded stroke, whereas eight (14.3%) underwent prophylactic reoperation, eight (14.3%) resulted in transient ischemia requiring reoperation, eight (14.3%) occluded without causing stroke, and 29 (51.8%) remained asymptomatic and did not progress to occlusion. Assuming that each of our eight patients who underwent prophylactic reoperation would have had a stroke if operation had not been carried out and our two unheralded strokes could have been prevented with more rigorous follow-up, RpCEADS might have prevented late stroke related to 10 (2.9%) of 348 arteries in 10 (3.9%) of 258 patients after surgery. All other cases of duplex-detected recurrent carotid stenosis or occlusion were asymptomatic or manifest by transient cerebral ischemia. Therefore RpCEADS cannot be justified as a means of preventing late strokes related to recurrent stenosis.

Carotid Stenosis

Critical carotid and vertebral arterial occlusive disease and cough syncope.

BACKGROUND AND PURPOSE: Cough syncope typically occurs in patients with known chronic lung disease. The mechanism usually involves a combination of decreased venous return, increased cerebrospinal fluid pressure, and secondary hypocapnia, all resulting in cerebral arterial vasoconstriction. Cough syncope has not in the past been associated with occlusive cerebrovascular disease. CASE DESCRIPTION: We describe a 50-year-old man with a 6-month history of episodes of loss of consciousness during paroxysms of coughing. Physical examination showed asymmetrical upper extremity blood pressures and carotid and subclavian artery bruits. Pulmonary function studies were normal. Ultrasound and angiography showed total occlusion of the left common carotid artery, right internal carotid artery, and right vertebral artery; tight stenosis of the right subclavian artery; and a hypoplastic left vertebral artery. The patient had a left subclavian-to-left common carotid artery bypass and has had no syncope since that time. CONCLUSIONS: To our knowledge, this is the first reported case of cough syncope and severe cerebrovascular disease in which surgery led to amelioration of symptoms. Cerebrovascular occlusive disease may contribute to cough syncope.

Aortography

Embolism from vertebral artery origin occlusive disease.

We report 10 patients with severe occlusive disease of the vertebral artery (VA) origin in the neck with intra-arterial embolism to the posterior circulation. The VA lesions in seven patients were complete occlusions, and three patients had severe atherostenosis. All patients had strokes in the vertebrobasilar territory. The most frequent recipient sites of intra-arterial embolism were the intracranial VA-posterior inferior cerebellar artery region (8), and the distal basilar artery (BA) and its superior cerebellar and posterior cerebral artery branches (7). Two patients had pontine infarction due to BA embolism. The most common clinical signs were due to cerebellar infarction. Atherosclerotic disease of the VA origin has features in common with disease of the internal carotid artery origin. Both have similar risk factors and demography, and each can cause strokes by intracranial intra-arterial embolism.

Aged

Comparison of descending phlebography with quantitative photoplethysmography, air plethysmography, and duplex quantitative valve closure time in assessing deep venous reflux.

To assess the role of noninvasive tests--quantitative photoplethysmography, air plethysmography, and quantitative duplex scanning, we compared a group of normal (group N, eight limbs) volunteers to patients with severe chronic venous insufficiency who were stratified according to the degree of reflux seen on the current "gold standard," descending phlebography. Group M (10 limbs) had mild (grades 0 to 2) reflux, and group S (10 limbs) had severe (grades 3 to 4) reflux as determined by phlebography. Quantitative photoplethysmography could identify normal from abnormal limbs but could not distinguish the severity of reflux. Air plethysmography was used to calculate venous filling index, ejection fraction, and residual volume fraction. Ejection fraction was the same in all groups. Venous filling index could not significantly distinguish the degree of reflux (group M vs group S) but increased as reflux increased. Residual volume fraction was considerably higher in group S. Quantitative duplex valve closure time was measured in the superficial femoral and popliteal veins, with the values added together in each limb to give a total valve closure time (TVCT). A TVCT value greater than or equal to 4 seconds correlated best with severe phlebographic reflux, with a sensitivity of 90%, a specificity of 94%, and an accuracy of 93%. This value was confirmed as the best test for venous reflux by receiver operating characteristic curve analysis. Thus in the evaluation of patients with severe chronic venous insufficiency who are candidates for phlebography and surgery, quantitative duplex measurement of TVCT gives the best noninvasive assessment of the severity of deep venous reflux.

Adult

Tumor necrosis factor facilitates regeneration of injured central nervous system axons.

The results of this study attribute to tumor necrosis factor (TNF) a role in regeneration of injured mammalian central nervous system (CNS) axons which grow into their own degenerating environment. This is the first time that a specific factor involved in axonal regeneration has been identified. The axonal environment is occupied mostly by glia cells, i.e., astrocytes and oligodendrocytes. Previous studies have shown that mature oligodendrocytes are inhibitory to axonal growth. Therefore, it seemed likely that application of a factor such as TNF, which has been shown to be cytotoxic to oligodendrocytes, would contribute to the creation of permissive conditions for axonal regeneration. In the present work, injured adult rabbit optic nerves were treated with human recombinant TNF (rhTNF). As a result, abundant newly growing axons (circa 9000, about 4% of the total estimated number of axons in an intact adult rabbit) were observed traversing the site of injury.

Animals

Prostaglandin E2 changes in the retina and optic nerve of an eye with injured optic nerve.

Changes in arachidonic acid metabolism were studied in the optic nerve, the chorioretina, and in the vitreous following crush injury to the optic nerve of rats. Crush injury led to: (i) a 3.9-fold increase in optic nerve prostaglandin type E2 in vitro production which peaked on day 5 and was followed by a gradual decline, but was still significantly higher than baseline levels by day 12; (ii) a two-fold increase in the chorioretina prostaglandin type E2 in vitro production which peaked on day 1, and resumed baseline levels by day 3; (iii) a 3.5-fold increase in vitreous prostaglandin type E2 levels on day 1 which remained at 1.5-2 times higher than baseline levels for the rest of the study period (12 days). The findings indicate that the pattern of changes in prostaglandin type E2 production by the optic nerve (consisting mostly of white matter) is different from that described for injured brain tissues. The prolonged accumulation of vitreal prostaglandin type E2 in eyes with damaged optic nerve may lead to undesirable effects on the retina beyond those directly manifested in the retina by altered axonal flow in the injured optic nerve.

Animals