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Biomedical subjects

J R Rubin

Publications and source records attributed to J R Rubin.

At least 19 recordsLinked to original sources

Crystallization and preliminary characterization of three crystal forms of human recombinant transforming growth factor-alpha.

Three crystal forms of human recombinant TGF-alpha have been grown from solutions containing 2-methyl-2,4-pentanediol. One of the forms belongs to the orthorhombic space group C222(1) and the other two belong to the monoclinic space group C2. Two of the crystal forms diffract to approximately 2.3 A Bragg spacings. X-ray diffraction data has been collected for all three forms. These data appear to be suitable for crystal structure determination, using either heavy atom isomorphous replacement methods or molecular replacement, for phase determination.

Crystallization

Structure of the anti-malarial drug primaquine diphosphate.

8-(4-Amino-1-methylbutylamino)-6-methoxyquinoline bis(dihydrogenphosphate), C15H23N3O2+.2(H2PO4)-, Mr = 455.35, triclinic, P1, Z = 2, a = 7.389 (6), b = 8.862 (4), c = 16.055 (10) A, alpha = 97.57 (2), beta = 100.21 (3), gamma = 77.01 (2) degrees, V = 1003.6 (5) A3, Dm = 1.495 (by flotation), Dx = 1.507 g cm-3, lambda (Cu K alpha) = 1.5418 A, mu(Cu K alpha) = 24.48 cm-1, F(000) = 480, room temperature, R = 0.068 for 3448 observed reflections. The above working cell is related to the reduced cell with angles alpha = 82.43, beta = 79.79 and gamma = 77.01 degrees by the transformation (-100/0 -10/001). Primaquine diphosphate was crystallized in the dicationic form with protonation on the quinoline ring nitrogen atom and on the terminal amino group. One dihydrogenphosphate anion is chelated by the quinoline ring and the butylamino side chain. The other dihydrogenphosphate anion is hydrogen bonded to the terminal amino group. The C(14) atom is nearly in the plane of the quinoline ring with a C(9)-C(8)-N(13)-C(14) torsion angle of 169 degrees. The butyl-diamino side chain is kinked by rotation about the C(14)-C(16) bond with a N(13)-C(14)-C(16)-C(17) torsion angle of -59 degrees. The C(15) methyl substituent is in line with the rest of the butyl chain. The terminal amino group N(19) is hydrogen bonded to three symmetry-related phosphate groups while N(1) and N(13) are 'chelated' to a fourth phosphate group.

Antimalarials

Lower-extremity amputation with immediate postoperative prosthetic placement.

To study the efficacy of an immediate postoperative prosthesis (IPOP) program, a retrospective review of 167 major lower-extremity amputations was performed. Patient enrollment in the IPOP program was based on the individual's potential for rehabilitation and participation in an aggressive postoperative physical therapy regimen, as determined by the surgeon, prosthetist, physical therapist, and social worker. Indications for amputation were intractable infection and/or severe unreconstructable arterial insufficiency. Sixty-five patients underwent 69 amputations with IPOP (59 below knee; 10 above knee). Successful program completion was defined as independent ambulation and occurred in 86% of those patients enrolled. The average interval from amputation to ambulation was 15.2 days for the below-knee amputees and 9.3 days for the above-knee amputees. Failure to complete the program occurred in 14% of patients and was due to noncompliance, stump infection, stump trauma, and death. The results of this review support the use of IPOP after major lower-extremity amputation.

Adult

A new approach for three-dimensional reconstruction of arterial ultrasonography.

This report describes a computerized approach that allows the creation of realistic three-dimensional arterial images from two-dimensional contiguous slices derived from a conventional ultrasound scan. Furthermore, the study assesses the method's feasibility and accuracy by performing in vitro cadaver artery three-dimensional reconstructions. Images are digitized into a computer, with a resolution of 512 x 480 pixels, and a dynamic range of 8 bits/pixel (256 gray scale). After edge enhancement with convolution filters through the original binary data, the intraluminal and outer edges are traced and converted to a polygon vector within a defined three-dimensional space. Serial cuts, 2 mm apart, are then "stacked" into a three-dimensional model, with interpolation of polyhedra between slices. Sixteen normal and arteriosclerotic distal aortic and common iliac arteries were obtained from fresh cadavers. Three-dimensional reconstruction models were compared with gross examination of the original artery. Anatomically accurate reconstructions were obtained, all with detailed surface information. Data analyzed included diameter, area, residual lumen, and percent stenosis. Pearson's coefficients determined for the pairs of data indicated excellent correlation (greater than or equal to 0.90) between separate measurements. With use of the described technology it is feasible to perform arterial three-dimensional reconstructions on a personal computer, with detailed and accurate surface information. The three-dimensional reconstruction method used can reliably and consistently reproduce the anatomic specimens.

Arteries

Peripheral vascular surgery.

Patients may present with a wide range of manifestations of arterial occlusive disease. The clinician must be able to assess the magnitude of the arterial flow diminution and thereby determine the appropriate treatment regimen. A careful history, physical examination, and pertinent noninvasive vascular laboratory tests should provide adequate information for the clinician to establish the severity of disease and the need to pursue a medical or surgical treatment plan. Patient evaluation must be carried out expeditiously, especially when limb-threatening conditions such as infection or gangrene exist, because these problems may progress rapidly and result in major lower extremity amputation.

Arterial Occlusive Diseases

Crystal structure of recombinant rabbit interferon-gamma at 2.7-A resolution.

The crystal structure of recombinant rabbit interferon-gamma was solved by the multiple isomorphous replacement technique at 2.7-A resolution and refined to a crystallographic R-factor of 26.2%. The interferon crystallizes with one-half of the functional dimer in the asymmetric unit, with the two polypeptide chains of the dimer related by a crystallographic 2-fold symmetry axis. The structure is predominantly alpha-helical with extensive interdigitation of the alpha-helical segments of the two polypeptide chains.

Amino Acid Sequence

Structure of the anti-cancer drug complex tetrakis (mu-acetato)-bis(1-methyladenosine)dirhodium(II) monohydrate.

[Rh2(C2H3O2)4(C11H16N5O4)2].H2O, Mr = 1024.6, triclinic, P1, a = 7.808 (3), b = 11.469 (4), c = 12.091 (2) A, alpha = 69.55 (2), beta = 79.46 (2), gamma = 76.61 (3) degrees, V = 980.7 (6) A3, Z = 1, Dx = 1.735 g cm-3, lambda (Cu K alpha) = 1.5418 A, mu = 77.6 cm-1, F(000) = 522, room temperature, R = 0.053 for 3638 unique reflections. Structure consists of two rhodium(II) ions in a metal--metal bond bridged by four acetate groups. The remaining axial coordination sites on the rhodium ions are coordinated to the N(7) positions of two 1-methyladenosine molecules.

Adenosine

Crystallization and preliminary x-ray diffraction studies of recombinant rabbit interferon-gamma.

Two different crystal forms of recombinant rabbit IFN-gamma were obtained under different crystallization conditions. The first, a tetragonal form with space group P43212 or P41212, was obtained through vapor phase equilibration using the sitting drop rods technique with ammonium citrate as the major precipitating agent. The unit cell dimensions of this crystal form are a = b = 82.1 A and C = 116.3 A. These crystals diffract to 2.8 A resolution and contain a dimer in the asymmetric unit. A second crystal form was obtained by the batch method at pH 8.0 using sodium chloride as the precipitating agent. The crystals are hexagonal, space group P6122 or P6522, and with unit cell dimensions of a = b = 58.0 A and c = 169 A. This form contains monomer in the asymmetric unit and diffracts to greater than 2.7 A resolution. Both forms appear to be eminently suitable for further analyses and crystal structure solution.

Animals

Unna's boot vs polyurethane foam dressings for the treatment of venous ulceration. A randomized prospective study.

Recent reports have suggested that polyurethane foam dressings provide a more rapid and comfortable healing of venous stasis cutaneous ulcerations than standard semirigid impregnated gauze dressings. This multi-institutional study consists of a randomized, prospective comparison of 36 consecutive patients who were treated with either polyurethane foam dressings (group 1, n = 17) or Unna's boot (group 2, n = 19) for venous ulceration of the lower extremities. Ulcer size ranged from 6.0 to 270 cm2 (mean, 32.2 cm2) for group 1 and 0.2 to 600 cm2 (mean, 76.0 cm2) for group 2. Nine (52.9%) of 17 group 1 patients withdrew from the study due to wound odor, while there was 100% compliance in group 2. Overall wound healing was superior in group 2 (18 [94.7%] of 19) as compared with group 1 (7 [41.2%] of 17) (chi 2 = 8.2). The rate of healing was also better in group 2 (0.5 cm2/d) than in group 1 (0.07 cm2/d). Contrary to published European trials, impregnated gauze dressings exhibited superior treatment results when compared with polyurethane foam dressings in the current study.

Bandages

Carotid endarterectomy for chronic retinal ischemia.

Carotid arterial disease may result in a variety of ischemic ocular problems that can eventually lead to permanent blindness. From 1984 to 1988, 18 patients underwent reconstruction of the carotid artery in an attempt to restore normal retinal arterial flow and, thereby, reverse or prevent progression of ischemic oculopathy. During a mean period of 21 months after carotid arterial reconstruction, subjective improvement in vision as well as a resolution in eye and periorbital pain was reported in 87.5 per cent of the patients. Measured visual acuity improved or stabilized in 94.4 per cent; macular photostress recovery times improved in 87.5 per cent, funduscopic examinations noted improvement or resolution in ischemic signs in 93.3 per cent and intraocular pressures improved in two of three patients. One patient experienced recurrent episodes of amaurosis fugax, which resolved after two weeks and did not recur. A second patient experienced an increase in intraocular pressures with visual deterioration, required laser photocoagulation after which the condition of the patient stabilized but only after significant visual impairment. Carotid arterial reconstruction is effective for the treatment of ischemic oculopathy and is most beneficial if performed early, before the onset of irreversible neovascular glaucoma.

Aged

Timing of carotid endarterectomy after acute stroke.

An arbitrary delay of at least 6 weeks before performing carotid endarterectomy after acute stroke has been recommended based on anecdotal reports. This prolonged interval may increase the danger of recurrent neurologic deficit before surgery. From September 1978 to September 1988, carotid endarterectomy was performed on 140 patients at variable intervals after stroke. Eleven patients had temporary stroke, which left 129 patients with neurologic symptoms that persisted for 3 weeks or had a cortical infarct on CT scanning. A prospective therapeutic protocol was applied to 82 patients admitted with acute stroke. They were observed until neurologic recovery reached a plateau, based on clinical observation by a neurologist, before performing angiography and carotid endarterectomy (group I). Forty-seven patients were not seen until after recovery from stroke was established (group II). At initial presentation, the severity of neurologic deficit was classified as mild, moderate, or severe in 31%, 58%, and 11%, respectively. Recovery before operation was registered as complete in 11%, mild residual in 66%, moderate residual in 21%, and severe residual in 2%. Group I patients (n = 82, 64%) were operated on within 6 weeks of stroke and group II (n = 47, 36%) were operated on at varying times after 6 weeks. No significant difference was found in the incidence of cerebrovascular events (1.2% vs 4.2%) and deaths (1.3% vs 2.1%) between groups I and II with respect to the timing of carotid endarterectomy, and no significant difference was found between patients operated on at 2, 4, 6, or more than 6 weeks after stroke.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease

Crystallization and preliminary X-ray diffraction studies of bovine recombinant immune interferon.

Reproducible conditions have been established for the crystallization of recombinant bovine immune interferon. Two cystalline forms of this protein were obtained. A tetragonal form, space group P422, with unit cell dimensions a = b = 59.0 A and c = 125.7 A and an orthorhombic form, space group P2(1)2(1)2(1), with unit cell dimensions a = 42.80 A, b = 79.90 A and c = 85.64 A were obtained under similar crystallization conditions. The orthorhombic form diffracts to 2.6 A resolution, contains a single interferon dimer in the asymmetric unit of structure and is suitable for X-ray diffraction analysis.

Animals

Femoral-tibial bypass for calcific arterial disease.

Overt calcification of the recipient artery and outflow bed has been regarded as a poor prognostic factor for femoral-distal arterial bypass patency and subsequent wound healing. In order to determine the short- and long-term limb salvage and graft patency rates achieved in these patients, the records of 35 patients undergoing 38 attempted femoral-tibial bypasses to a calcified recipient artery were reviewed. Two patients were unreconstructable at the time of surgery. Thirty-one of the 36 operations (86 percent) were performed using in situ saphenous vein bypass techniques, 3 were performed with polytetrafluoroethylene (PTFE), 1 with a composite sequential, and 1 with a composite vein graft. Immediate limb salvage was achieved in 31 of 36 limbs (86 percent). Five early below-knee amputations (14 percent) were required, two due to graft thromboses and three due to progressive foot necrosis despite patent grafts. One patient (3 percent) died secondary to sepsis. Three-year primary graft patency and limb salvage rates did not differ significantly from bypasses to noncalcified vessels. Femoral-distal bypass in the presence of overt calcific arterial disease may be successfully accomplished and offers an excellent prognosis for long-term graft patency and limb salvage.

Adult

Do operative results justify tibial artery reconstruction in the presence of pedal sepsis?

An aggressive surgical approach is warranted in all patients with a salvageable weight-bearing pedal surface. Although patients with pedal sepsis (69 limbs) had a lower 30 day limb salvage rate and higher morbidity and mortality rates than those without sepsis (34 limbs), the long-term salvage rates of both groups by life table analysis were not statistically different and remained at the 70 percent level 3 years postoperatively. Peribypass amputation, debridement of the septic foot, or both should be carried out when deemed necessary to decrease the risk of septic complications after revascularization. Other risk factors such as diabetes or heart disease had no bearing on the short-term results of bypass in either the septic or nonseptic group. Autogenous saphenous vein is preferable to synthetic bypass material, especially in patients with ongoing infection. Lastly, even though the medical climate in 1988 must reflect the stark reality of economic restrictions imposed by third-party payors, optimal patient care remains our primary responsibility. We believe that long-term pedal salvage, as achieved by arterial reconstruction, aggressive wound management, and rehabilitation, attains this goal.

Amputation, Surgical

Effect of hemodilution on brain tissue during global ischemia.

This study evaluates the effect of blood volume and hematocrit changes on brain tissue during temporary global ischemia. Normal saline was administered intravenously to 55 gerbils to achieve hypo-, normo-, and hypervolemic hemodilution and uniform 30% hematocrit reduction. Each group had unilateral carotid artery ligation and temporary (20 minute) contralateral carotid occlusion. After ten days or death, brains were harvested, preserved in formalin, sectioned in a manner which provided adequate samples of both cortex and hippocampus, and stained with H&E and luxol fast blue. They were then examined and staged microscopically for white and gray matter infarction, edema, and neuronal injury and loss. Histologic studies were performed in a randomized and blinded manner and were classified by one of four categories: normal, minimal, moderate, and severe changes. Three of ten (30%) controls survived ten days but had severe neuronal loss, minimal cerebral edema and a minimal to moderate number of white matter strokes. Survival was best in animals treated with hypovolemic hemodilution (43%). Other rates were: normovolemic (33%), controls (30%), and hypervolemic (8.3%). The degree of brain tissue damage was markedly less in the normovolemic group. In this model, normovolemic hemodilution followed by hypovolemic hemodilution offered the best overall cerebral protection during global ischemia.

Animals

Carotid endarterectomy in a metropolitan community: the early results after 8535 operations.

Several retrospective community surveys have provoked speculation concerning the safety of carotid endarterectomy (CEA) throughout the United States. To address this serious issue, surgical outcome was calculated for 8535 CEAs entered prospectively into a computer registry by 51 trained vascular surgeons in a large metropolitan area from 1973 to 1985. A total of 7480 procedures (88%) were performed for symptomatic lesions and 1055 (12%) were performed for asymptomatic stenosis or ulceration. There were 178 operative strokes (2.1%) and 135 early deaths (1.6%), for a combined morbidity-mortality rate of 3.2%. Fatal events were attributed to cardiac disease in 0.7%, neurologic complications in 0.6%, and other causes in 0.3%. The stroke rate (n = 148; 2.0%) in symptomatic patients was better than that in asymptomatic patients (n = 30; 2.8%) (chi 2 = 5.2; p less than 0.025), but the combined morbidity-mortality rates (2.9% and 3.7%) were not statistically different. The incidence of stroke reported by surgeons who performed more than 5 CEAs annually (1.7%) was statistically superior to the stroke rate (3.4%) among those with less experience (chi 2 = 37.1; p less than 0.0001). Nevertheless, both groups had acceptable results that were consistent with their training and continued interest in vascular surgery.

Aged

Combined thrombolytic therapy and percutaneous transluminal angioplasty for treatment of complex arterial graft thrombosis--a case report.

Combined catheter-directed thrombolytic therapy followed by percutaneous transluminal angioplasty (PTA) was successfully performed for the treatment of a thrombosed complex mesenteric artery bypass graft resulting from an anastomotic stenosis. Restenosis of the graft due to neointimal hyperplasia was subsequently treated by PTA, with resultant long-term patency. This approach is an attractive alternative to surgical thrombectomy and graft revision, especially in patients who are poor surgical risks owing to concurrent medical problems.

Aged

Management of failed prosthetic grafts at the time of major lower extremity amputation.

During a 2-year period 75 patients underwent 77 major lower extremity amputations for arterial insufficiency deemed untreatable by reconstruction (36 primary and 41 after failed infrainguinal arterial bypass). Patients with nonfunctional prosthetic grafts were randomized prospectively to either partial graft removal or complete graft removal, performed simultaneously with amputation, to determine which technique more effectively reduces delayed wound healing, stump infection, operative revision, and process-related death. Patients with known graft and deep wound infection were excluded from this review, as were patients who had positive graft cultures at the time of amputation. Partial graft removal resulted in an increased rate of delayed wound healing (47.8% vs 7.7%; chi 2 5.9, p less than 0.025) and secondary stump infection (39.1% vs 7.7%; chi 2 4.4, p less than 0.05), when compared with complete graft removal. The operative revision and process-related mortality rates were also higher in limbs that had partial graft removal, although not statistically significant. The operative morbidity and mortality rate was no greater in the group with complete graft removal, although the mean operative time was nearly doubled (1.4 vs 2.6 hours). Therefore we recommend that all nonfunctional prosthetic graft material be removed concomitant with major lower extremity amputation to avoid the excessive number of wound healing and suppurative complications that are encountered when residual graft material is present in the amputation stump.

Amputation, Surgical