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Biomedical subjects

D Silver

Publications and source records attributed to D Silver.

At least 55 records · Page 3Linked to original sources
PubMed1996

Analysis of p21WAF1/CIP1 in primary bladder tumors.

The p21WAF1/CIP1 gene is regulated by p53 and encodes a cyclin-dependent kinase (Cdk)-inhibitor involved in senescence and cell quiescence. The role of p21 as a negative regulator of cell proliferation suggests that it may function as a tumor suppressor gene. However, only a few mutations of the p21WAF1/CIP1 gene have been reported to date. In order to assess potential p21WAF1/CIP1 gene alterations in human bladder cancer, we have examined this gene and its encoded product in a well-characterized cohort of 27 primary bladder tumors. Mobility shifts by single-strand conformation polymorphism in the p21WAF1/CIP1 gene were identified in 2 cases. Sequencing analyses revealed that one of these cases had point mutations in the 3' untranslated region, while the other case had a frame shift mutation at positions 322 (C to A) and a deletion of 8 nucleotides (323-->331; CCG-->ACG, codon 81 Arg-->Thr) that produced a stop signal at codon 83 (Gly--Stop). This tumor had a p21-negative phenotype by immunohistochemistry, but did not lose any allele. We further characterized these cases by the study of TP53 mutations using single-strand conformation polymorphism (PCR-SSCP) and sequencing, as well as immunohistochemical assays. Seven mobility shifts were identified and seven cases showed p53 nuclear accumulation. The two cases displaying mutated p21WAF1/CIP1 had wild-type TP53. It is concluded that p21WAF1/CIP1 gene aberrations are infrequent in bladder carcinoma but may be occasionally identified in primary bladder tumors.

Aged↗
PubMed1995

Proposed simulation of volumetric image navigation using a surgical microscope.

This paper describes a simulated surgical setup based on modern, frameless stereotactic techniques that enable surgeons to visualize the field of view of the surgical microscope, overlaid with the segmented volumetric medical images, of a localized area of the patient's head. Using this "true three-dimensional" navigation system, the surgeon visualizes the surgical site while exploring the inner layers of the patient's anatomy via the surgical microscope. It also allows the surgeon to "fly through," and around, the site of the surgery to visualize several alternatives and qualitatively choose what he or she believes is the best surgical approach. Moving surgical devices are tracked with stereo vision cameras, allowing determination of their spatial relationship to the target lesion.

Brain↗
PubMed1995

Coexisting extraadrenal pheochromocytoma and renal artery stenosis: a case report and review of the pathophysiology.

The authors report the case of an 8-year-old boy with coexisting malignant extraadrenal pheochromocytoma and ipsilateral renal artery stenosis, severe hypertension, normal urinary vanillylmandelic acid levels, and elevated catecholamines and renin levels. Reported mechanisms of the stenosis are reviewed. The interrelationships of catecholamines, renin, and angiotensin and their effects on renal vasculature are discussed.

Catecholamines↗
PubMed1995

Effect of pentoxifylline on tissue injury and platelet-activating factor production during ischemia-reperfusion injury.

PURPOSE: Pentoxifylline lessens the metabolic derangements associated with ischemia-reperfusion injury. This study evaluated the effects of pentoxifylline on platelet-activating factor (PAF) production and tissue injury during skeletal muscle ischemia-reperfusion injury. METHODS: The isolated canine gracilis muscle model was used. Group 1 muscles were subjected to 5 hours of ischemia and 20 hours of reperfusion (n = 10); group 2 muscles received pentoxifylline, 15 mg/kg, systemic infusion 10 minutes before reperfusion (n = 6); group 3 muscles received pentoxifylline, 25 mg/kg, systemic infusion 10 minutes before reperfusion (n = 6). PAF was measured from muscle venous effluent by the scintillation proximity assay method. Muscle injury was assessed by vital staining and planimetry. RESULTS: PAF levels in group 2 were decreased at 10, 15, and 30 minutes of reperfusion compared with group 1 but did not reach significance. PAF levels in group 3 were decreased at all times of reperfusion compared with group 1 but attained significance only at 10 minutes of reperfusion (p < 0.05). No significant differences in muscle weight were noted among the three groups. No differences in the extent of muscle necrosis was observed between group 1 (77.26% +/- 20.38%) and group 2 (60.49% +/- 23.97%) (p = 0.08); there was a significant reduction in the extent of muscle necrosis in group 3 (44.55% +/- 21.47%) compared with group 1 (p < 0.05). CONCLUSIONS: The administration of pentoxifylline at 25 mg/kg before reperfusion of ischemic skeletal muscle decreased significantly the extent of muscle necrosis and PAF levels in the venous effluents at all times of reperfusion (significantly at 10 minutes). These results suggest that pentoxifylline may decrease tissue injury of ischemia-reperfusion by inhibiting the production of PAF during critical periods of reperfusion.

Animals↗
PubMed1995

Neodymium:yttrium-aluminum-garnet laser fusion of endarterectomy flaps.

PURPOSE: This study evaluated the efficacy of neodymium:yttrium-aluminum-garnet laser welding of flaps in canine arteries and in securing the distal flap during human carotid endarterectomy. METHODS: Endarterectomy flaps were created in both common carotid and both common femoral arteries in 12 dogs. The flaps were repaired with either the neodymium:yttrium-aluminum-garnet laser or with 6-0 polypropylene sutures. The arteries were removed after duplex scanning at either 7 or 28 days. Eighteen high carotid endarterectomy flaps in 16 patients have been subsequently secured with the laser welding technique. RESULTS: Laser repairs (125 +/- 19 joule) of the canine arteries were completed more quickly than suture repairs (mean 25 seconds vs 135 seconds, respectively; p < 0.04). Duplex ultrasonography revealed no discernable differences between the two groups of arteries. Arteries studied at 7 days revealed three microscopic flaps (two suture, one laser), more subintimal fibroblastic proliferation in suture than laser-repaired carotid arteries (3: 1, p = 0.0530), and similar amounts of inflammation in suture- and laser-repaired arteries. Arteries studied at 28 days revealed one microscopic intimal flap (suture-repaired); equal fibroblastic and inflammatory responses in suture- and laser-repaired vessels; and no evidence of laser thermal injury. Eighteen carotid endarterectomy flaps have been successfully fused with no immediate or long-term complications in 16 patients (follow-up of 0 to 24 months). CONCLUSION: Laser fusion appears to be a safe and effective method for securing distal carotid endarterectomy flaps.

Animals↗
PubMed1995

Do patients with the heparin-induced thrombocytopenia syndrome have heparin-specific antibodies?

PURPOSE: Patients with the heparin-induced thrombocytopenia syndrome (HIT) have heparin-associated antibodies (HAb+), which, in the presence of heparin, are responsible for platelet activation and aggregation. This study addressed the questions: (1) are the antibodies specific for heparin; and (2) how do the antibodies cause platelet aggregation? METHODS: Plasmas from 79 patients with HIT were divided into seven plasma samples: HAb+ plasma sample 1 (24 pooled plasmas); HAb+ plasma sample 2 (50 pooled plasmas); and HAb+ plasma samples 3 through 7 (individual plasmas). Normal patient plasmas were used as controls (HAb-). RESULTS: All seven HAb+ plasma samples caused platelet aggregation (PLA) in the presence of heparin and formed a precipitation line with heparin in gel immunodiffusion plates (HAb- plasmas did neither). The HAb+ plasma samples reacted with heparin, as determined by immunoprecipitation in sodium dodecylsulfate-polyacrylamide gel, with the production of a band at 50 kd (no band with HAb- plasmas). The plasma samples 1 and 2 were passed over heparin sepharose beads three times; the unabsorbed plasmas produced 3+ PLA, the first effluent produced 2+ PLA, and the second and third effluents produced no PLA. The heparin sepharose beads stained 3+, 2+, and 1+, after the respective passages, with fluorescein-labeled goat sera containing anti-human immunoglobulin G antibody. HAb+ plasma samples were digested with pepsin to separate the F(ab')2 fragments from the Fc fragments. The F(ab')2 fragments reacted with heparin as determined by immunoprecipitation in sodium dodecylsulfate-polyacrylamide gel with the production of a band at 25 kd, but did not cause PLA in the presence of heparin. CONCLUSION: Patients with HIT have heparin-specific antibodies that react with heparin in a classic F(ab')2 reaction and require the Fc fragment for platelet aggregation.

Absorption↗
PubMed1994

Rural vascular trauma: a twenty-year review.

A 20-year review documented 248 vascular injuries in 210 patients from principally rural areas. The average time between injury and treatment from 1970 to 1983 was 6 hours. Between 1983 to 1990, when 46% of patients were transported by helicopter, the average delay was 4 hours. Blunt trauma (41%, with 29% motor vehicle accidents and 12% farm/industrial accidents) caused the most severe injuries and accounted for most amputations (89%) and deaths (80%). All of the blunt trauma patients had associated injuries. Penetrating injuries occurred in 59% of the patients and accounted for 11% of the amputations and 20% of the deaths. Extremity vessels were injured 73% of the time (upper extremity, 47%; lower extremity, 26%). Eighty-seven percent of the vessels injured were arteries and 13% were major venous injuries. Preoperative arteriograms were obtained in 30% of our patients. Vascular injury was determined in the others at the time of operative exploration. Vascular repair included direct anastomosis or lateral suture repair (51%), autogenous vein graft (16%), synthetic graft (6%), and ligation (19%). Primary amputation and thrombectomy were other (8%) initial treatments. In the past 10 years concomitant major peripheral venous injuries were repaired in six patients (one amputation) and ligated in one patient (no amputation). The mortality rates (4.8% total) for patients with blunt and penetrating trauma were 9.3% and 1.6%, respectively. Survival rates have not improved since the implementation of a helicopter transport system in 1983, but the amputation rate declined from 18% to 7%.

Adolescent↗
PubMed1994

Visualizing collagen fibril growth.

Collagen fibrils are among the most abundant protein polymers in living organisms. While the longitudinal packing of molecules in the fibrils has been agreed on for many years, there is continuous disagreement over the lateral packing. In this work, we describe a set of computer graphics programs that can be used to visualize fibril packing and simulate fibril growth. An example of a model and simulation are presented.

Collagen↗
PubMed1994

Site-specific mutagenesis of the nodule-infected cell expression (NICE) element and the AT-rich element ATRE-BS2* of the Sesbania rostrata leghemoglobin glb3 promoter.

Sesbania rostrata leghemoglobin glb3 (Srglb3) promoter sequences responsible for expression in infected cells of transgenic Lotus corniculatus nodules were delimited to a 78-bp Dral-Hinfl fragment. This region, which is located between coordinates -194 to -116 relative to the start codon of the Srglb3 gene, was named the nodule-infected cell expression (NICE) element. Insertion of the NICE element into the truncated nopaline synthase promoter was found to confer a nodule-specific expression pattern on this normally root-enhanced promoter. Within the NICE element, three distinct motifs ([A]AAAGAT, TTGTCTCTT, and CACCC[T]) were identified; they are highly conserved in the promoter regions of a variety of plant (leg)hemoglobin genes. The NICE element and the adjacent AT-rich element (ATRE-BS2*) were subjected to site-directed mutagenesis. The expression patterns of nine selected Srglb3 promoter fragments carrying mutations in ATRE-BS2* and 19 with mutations in the NICE element were examined. Mutations in ATRE-BS2* had varying effects on Srglb3 promoter activity, ranging from a two- to threefold reduction to a slight stimulation of activity. Mutations in the highly conserved (A)AAAGAT motif of the NICE element reduced Srglb3 promoter activity two- to fourfold, whereas mutations in the TCTT portion of the TTGTCTCTT motif virtually abolished promoter activity, demonstrating the essential nature of these motifs for Srglb3 gene expression. An A-to-T substitution in the CACCC(T) motif of the NICE element also abolished Srglb3 promoter activity, while a C-to-T mutation at position 4 resulted in a threefold reduction of promoter strength. The latter phenotypes resemble the effect of similar mutations in the conserved CACCC motif located in the promoter region of mammalian beta-globin genes. The possible analogies between these two systems will be discussed.

Base Sequence↗
PubMed1993

Spontaneous common carotid artery dissection.

A case of a symptomatic spontaneous common carotid artery dissection that occurred several months after an ipsilateral carotid endarterectomy is presented. The case was successfully managed with resection of the dissected common carotid artery and placement of an interposition saphenous vein graft. Examination of the specimen demonstrated cystic medial degeneration. Postoperative duplex scans of the carotid artery and graft have been normal. The data obtained from this case and a review of the seven previously reported cases suggest that surgical management of symptomatic spontaneous common carotid artery dissections can be accomplished safely. Surgical management of these dissections is recommended for patients with symptoms and for those without symptoms who have aneurysmal changes in the dissected segment.

Aged↗
PubMed1993

Can low molecular weight heparins and heparinoids be safely given to patients with heparin-induced thrombocytopenia syndrome?

BACKGROUND: Low molecular weight heparin (LMWH) and heparinoids have been offered as alternatives to unfractionated heparin (UH) to patients with heparin-associated antiplatelet antibodies (HAAb) and heparin-induced thrombocytopenia syndrome (HIT). Some of these patients have had continued HIT in the presence of the UH substitutes. It would seem important to know whether the heparin substitute is likely to cause patients' platelets to aggregate before administering the substitute to patients with HAAb. METHODS: Patients with HIT were identified as having HAAb by positive platelet aggregometry testing with commercial UH. Plasmas from 51 patients with HAAb were tested for the ability to aggregate platelets in the presence of two LMWHs (Mono-Embolex NM and Fragmin) and one heparinoid (Org 10172). RESULTS: The proportions of plasmas reacting to each UH substitute are Mono-Embolex NM, 60.8%; Fragmin, 25.5%; and Org 10172, 19.6%. Although Fragmin and Org 10172 aggregated platelets in the presence of HAAb significantly less often than Mono-Embolex NM (p < 0.001), a patient with HAAb has a substantial chance of reacting to one of these UH substitutes. CONCLUSIONS: Before giving a LMWH or heparinoid to a patient with HAAb, one should determine with in vitro testing that the patient's HAAb will not cause platelet aggregation in the presence of the heparin substitute.

Adolescent↗
PubMed1993

Effects of donor characteristics and platelet in vitro time and temperature on platelet aggregometry.

PURPOSE: This study was undertaken to determine whether platelet donor characteristics and the duration and temperature of platelet storage affect platelet aggregation. METHODS: Half of each platelet-rich plasma sample, obtained from 42 healthy volunteers, was maintained at 37 degrees C and the other half at 25 degrees C. Aggregation was stimulated with adenosine diphosphate (ADP), epinephrine, or collagen 1, 2, 4, and 6 hours after platelet donation. The lag time, slope of the aggregation curve, and percent peak aggregation were determined for each aggregation test. RESULTS: Age, sex, time of donation, smoking status, estrogen replacement, and menstruation did not significantly influence platelet aggregation. Storage time and temperature had a major influence on platelet reactivity, with the reactivity decreasing with prolonged storage and higher storage temperatures. Peak ADP-induced aggregation for platelets stored at 37 degrees C was significantly less (p < 0.0002) than the values obtained for ADP aggregation at 25 degrees C. Collagen-stimulated peak aggregation of platelets maintained at 37 degrees C for 4 and 6 hours was also significantly less than the corresponding values at 25 degrees C. Epinephrine-stimulated aggregation produced similar results, with peak platelet aggregation decreasing with time (50.3% +/- 2.9% at 6 hours compared with 38.5% +/- 3.7% at 2 hours at 25 degrees C) and high storage temperatures (there was less aggregation by platelets stored at 37 degrees C at each time period studied). CONCLUSIONS: It is recommended that platelet-rich plasma for platelet aggregation testing be maintained at room temperature and be used between 2 and 4 hours after platelet donation.

Adenosine Diphosphate↗
PubMed1992

Helical model of nucleation and propagation to account for the growth of type I collagen fibrils from symmetrical pointed tips: a special example of self-assembly of rod-like monomers.

A model was developed to account for the recent observations indicating that type I collagen fibrils assembled in vivo grow from symmetrical pointed tips. The essential features of the model are (i) a distinctive structural nucleus forms at each end of a growing fibril and growth of the fibril then proceeds by propagation of the two structural nuclei, (ii) the two structural nuclei have similar spiral or helical conformations, and (iii) assembly of each structural nucleus requires two kinds of specific binding steps defined as 3.4 D-period and 0.4 D-period overlaps, but propagation of the nucleus requires only the 3.4 D-period binding step.

Collagen↗
PubMed1992

Heparin-induced thrombocytopenia in open heart surgical patients: sequelae of late recognition.

Most patients undergoing open heart operations have had exposure to heparin for diagnostic and/or therapeutic procedures. Heparin antibody formation and heparin-induced thrombocytopenia with repeat heparin administration can cause high morbidity and mortality from thrombotic complications, especially when delay in diagnosis occurs. From 1981 to 1991, heparin-induced thrombocytopenia was diagnosed in 82 of 4,261 open heart surgical patients (1.9%). Platelet counts less than 100 x 10(9)/L (100,000/microL) or new or recurring thrombotic events prompted suspicion of heparin-induced thrombocytopenia. Heparin-dependent antibody was diagnosed preoperatively in 12 patients (group I) and postoperatively in 70 patients (group II). Heparin was not given postoperatively in group I patients, and complications in this group were limited to bleeding in 3 patients. There were no thromboembolic events and all patients survived. Group II patients had late recognition of heparin-dependent antibody postoperatively, and heparin exposure was continued for varying periods postoperatively. Thirty-seven group II patients (53%) had bleeding complications and 31 (44%) had thromboembolic complications. These complications led to death in 23 group II patients (33%). Heparin-dependent antibody may occur in patients having open heart operations and is a major cause of morbidity and mortality if not diagnosed early with cessation of heparin therapy.

Acute Kidney Injury↗
PubMed1992

Heparin-induced thrombocytopenia in the newborn.

This pilot study was initiated to determine whether heparin-induced thrombocytopenia occurs in the newborn and whether thromboembolic complications in the newborn could be related to heparin-induced thrombocytopenia. Thirty-four infants in whom thrombocytopenia (less than 70,000/mm3) (n = 23), precipitous (30% to 50%) fall in platelet count (n = 5), or thromboses (n = 6) developed while they were receiving heparin were studied. Heparin-associated antiplatelet antibodies were demonstrated in 14 infants by platelet aggregation testing. The average gestational age (29 +/- 6 weeks); birth weight (1300 +/- 945 gm); and platelet count at birth (234,000/mm3 +/- 111,000/mm3) of these 14 infants did not differ statistically from the 20 infants without heparin-associated antiplatelet antibodies. An umbilical artery catheter was inserted in all infants except a single patient from each group. Aortic thrombosis was documented by abdominal ultrasonography in 11 of 13 (85%) infants with heparin-associated antiplatelet antibodies. One patient died with a midgut volvulus before the aorta could be examined. Five aortic thromboses were detected in the 20 infants without heparin-associated antiplatelet antibodies. Bleeding was not associated with the heparin-induced thrombocytopenia. One patient with previously demonstrated thrombocytopenia and heparin-associated antiplatelet antibodies had recurrent thrombocytopenia when reexposed to heparin; her platelet count recovered after heparin withdrawal. Thus heparin-induced thrombocytopenia does occur in preterm and term infants receiving heparin and is associated with arterial thromboses. Therefore infants receiving any form or amount of heparin must be carefully monitored for heparin-induced thrombocytopenia.1+

Autoantibodies↗
PubMed1992

Axillopopliteal bypass for limb salvage.

Forty-one axillopopliteal bypass grafts have been placed in 30 patients for limb salvage in the past 12 years. The mean patient age was 65.6 years; 8 were women; 19 smoked; and six had diabetes. Sixteen grafts were straight axillopopliteal bypass grafts, and 25 were sequential axillopopliteal bypass grafts. Cumulative life-table primary patency rates at 1, 2, and 3 years were 70%, 56%, and 43%, respectively; secondary patency rates were 73%, 57%, and 50%, respectively. Corresponding limb salvage rates were 86%, 69%, and 69%, respectively. Ringed polytetrafluoroethylene (PTFE) graft patency at 3 years was 61% versus 40% for unsupported PTFE grafts (p = 0.35). Ringed PTFE axillofemoral grafts with sequential femoropopliteal saphenous vein grafts had a 3-year patency of 67%. Graft patency was restored in 25% of occluded grafts by thrombectomy and in 80% of occluded grafts by thrombectomy with graft revision (p = 0.21). Cumulative 3-year patient survival was 48%. The 30-day operative mortality rate was 20%; patients operated on for graft infection had a 30-day operative mortality rate of 36%. The data support the use of axillopopliteal bypass for limb salvage when standard revascularization techniques are contraindicated. Long-term patency is enhanced by use of externally supported PTFE and sequential femoropopliteal saphenous vein.

Aged↗