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Biomedical subjects

J R Rubin

Publications and source records attributed to J R Rubin.

69 records · Page 4Linked to original sources

Peripheral vascular disease: treatment and referral of the elderly. Part II.

The noninvasive methods of examining the extracranial cerebrovascular system are undergoing many changes, with innovations occurring frequently. The reliability of the different testing methods varies, but is generally reported to be in the range of 80 to 95%. One of the most important aspects in caring for patients with atherosclerotic occlusive disease, whether they are being monitored for disease progression or have already undergone a vascular reconstructive procedure, is lifelong follow-up.

Aged↗

Management of infection of major amputation stumps after failed femorodistal grafts.

A retrospective review was performed of 174 patients who underwent 199 lower-extremity amputations for unreconstructable vascular insufficiency from 1976 to 1983 at the Northwestern University Medical Center. This study was initiated to identify the cause of amputation wound healing complications and secondary ascending prosthetic graft infection, as well as to propose a plan of management for the failed prosthetic grafts at the time of major limb amputation. Ninety-eight amputations were performed primarily, 12 were performed secondary to graft infection, and 89 were performed in patients who had previously undergone infrainguinal arterial bypass procedures. At the time of amputation, graft management consisted of high transection and suture ligation, allowing the graft to retract into the substance of the stump and away from the skin suture line and weight-bearing area of the limb. Delayed stump healing was noted to occur more commonly in the group who had undergone previous bypasses as opposed to those who had undergone primary amputation (34.8% versus 14.3%). Fourteen graft infections developed in 89 patients after amputation (15.7%), which is significantly higher than the overall 1.4% incidence of lower-extremity bypass infections that occurred during the same interval in patients with intact extremities. In addition, it was found that when infected grafts in amputated limbs were completely removed, stump healing without recurrent wound and graft sepsis was better than when treated locally or with partial graft removal. We therefore recommend removal of a thrombosed graft with an infected wound or an infected graft at the time of major limb amputation to decrease the incidence of wound complications and graft infection.

Amputation Stumps↗

The relevance of arterial wall microbiology to the treatment of prosthetic graft infections: graft infection vs. arterial infection.

One potential, but poorly studied source for intraoperative contamination of vascular grafts is the native artery to which the prosthetic graft is attached. The purpose of this study was to analyze the relationship between arterial wall microbiology and graft infection. Between July 1, 1981, and March 31, 1982, arterial specimens were cultured from 88 (30%) of 298 patients undergoing clean, elective arterial reconstructive procedures. Control cultures were obtained from adjacent adipose or lymph node tissue. Positive cultures were obtained from 38 of 88 (43%) of the arterial walls cultured but from none of the control cultures (0 of 20) (p less than 0.001). The most common organism cultured was Staphylococcus epidermidis (27 of 38; 71%). Our overall graft infection rate since January 1, 1981, is 0.9% (3 of 335). All three graft infections occurred in patients with positive arterial cultures. Arterial and graft cultures were also obtained from 20 patients treated for 22 graft infections over the past 13 years. Organisms recovered included staphylococcal species (36%), enteric organisms (46%), and mixtures of the two (18%). These patients with culture-positive graft infections were divided retrospectively into two groups: those with positive and those with negative arterial cultures. Positive arterial cultures were associated with suture line disruption in 8 of 14 cases (57%), but there were no arterial disruptions in patients with negative cultures (0 of 8) (p less than 0.01). These data document a significant correlation between positive arterial wall cultures and subsequent prosthetic infection and also suggest that infection involving the arterial wall is a major determinant of the morbidity and mortality associated with the treatment of prosthetic graft sepsis.

Arteries↗

Crosslinking of tRNAs by the carcinostatic agent dirhodium tetraacetate.

A crystalline complex of yeast tRNA(phe) and dirhodium tetraacetate (DRTA) was prepared and its X-ray structure determined. The bifunctional DRTA forms an intermolecular cross-link between the N(1) position of adenine A36 in the anticodon triplet and possibly a ribose hydroxyl group of residue A76 at the 3' terminus of a symmetry related tRNA molecule. The rhodium complex apparently shows a preference for binding to the N(1) position of adenine in a single strand region of the tRNA molecule.

Antineoplastic Agents↗

Similar binding of the carcinostatic drugs cis-[Pt(NH3)2Cl2] and [Ru(NH3)5Cl] Cl2 to tRNAphe and a comparison with the binding of the inactive trans-[Pt(NH3)2Cl2] complex - reluctance in binding to Watson-Crick base pairs within double helix.

A comparative study of the binding of square planar cis- and trans-[Pt(NH3)2Cl2] complexes and the octahedral [Ru(NH3)5(H2O)]3+ complex to tRNAphe from yeast was carried out by X-ray crystallography. Both of the carcinostatic compounds, cis-[Pt(NH3)2Cl2] and [Ru(NH3)5(H2O)]3+ show similarities in their mode of binding to tRNA. These complexes bind specifically to the N(7) positions of guanines G15 and G18 in the dihydrouridine loop. [Ru(NH3)5(H2O)]3+ has an additional binding site at N(7) of residue G1 after extensive soaking times (58 days). A noncovalent binding site for ruthenium is also observed in the deep groove of the acceptor stem helix with shorter (25 days) soaking time. The major binding site for the inactive trans-[Pt(NH3)Cl2] complex is at the N(1) position of residue A73, with minor trans-Pt binding sites at the N(7) positions of residues Gm34, G18 and G43. The similarities in the binding modes of cis-[Pt(NH3)2Cl2] and [Ru(NH3)5(H2O)]3+ are expected to be related to their carcinostatic properties.

Base Composition↗

X-ray diffraction study of the zinc(II) binding sites in yeast phenylalanine transfer RNA. Preferential binding of zinc to guanines in purine-purine sequences.

An X-ray diffraction study of a zinc(II) complex of tRNAPhe from yeast reveals the present of five zinc-binding sites on the tRNA molecule. Two of the cooperatively bound Mg2+ in the native tRNA structure are replaced by Zn2+. The remaining sites involve direct coordination of zinc to the N7 position of tRNA guanine bases, G15, G43 and HG45. Thus, zinc displays a high specificity for binding to guanine bases in purine-purine sequences.

Base Sequence↗

Lead ion binding and RNA chain hydrolysis in phenylalanine tRNA.

Crystalline complexes of yeast phenylalanine tRNA and Lead (II) ion were prepared by soaking pregrown orthorhombic crystals of tRNA in saturated lead chloride solutions. The locations of tightly bound lead ions on the tRNA were determined by difference Fourier methods. There are three major lead binding sites; two of these replace tightly bound magnesium ions in the native tRNA structure. Site I is located in the dihydrouridine loop of the molecule adjacent to phosphate P18 which is specifically cleaved by lead. This is evident from changes observed in the Pb-native difference electron density maps. A possible mechanism for lead ion hydrolysis of the polynucleotide chain is proposed.

Binding Sites↗

Diagnosis of choledocholithiasis.

A review of the records of 75 consecutive patients with a discharge diagnosis of choledocholithiasis has been conducted. Clinical assessment as well as laboratory assessment of patients who are suspected of having common duct calculi continues to present significant problems in diagnostic accuracy. More than 90 per cent of the patients who presented with Charcot's triad of pain, fever and jaundice had common duct calculi; however, only one-fourth of the patients in our study with choledocholithiasis had this combination of symptoms. Imaging techniques before operation are associated with a significant incidence of false-negative and false-positive findings. Palpation of the common duct and cholangiography at the time of operation remain the most reliable means of detecting choledocholithiasis.

Adult↗

A pharmacologic and toxicological study of amygdalin.

Six patients with advanced cancer were treated with amygdalin (laetrile) at dosages similar to those employed by laetrile practitioners. Amygdalin given intravenously at 4.5 g/sq m/day was largely excreted unchanged in the urine and produced no clinical or laboratory evidence of toxic reaction. Amygdalin given orally at 0.5 g three times daily produced significant blood cyanide levels to 2.1 microgram/mL. No clinical or laboratory evidence of toxic reaction was seen in the six patients taking oral amygdalin at this dosage. One patient, however, challenged with a large intake of raw almonds, had transient symptoms of cyanide toxic reaction with escalating blood cyanide levels. This small study indicates that amygdalin in the doses employed produces few clinical side effects. A definite hazard of cyanide toxic reaction must be assumed, however, and possible long-term side effects remain unknown.

Administration, Oral↗

A simple procedure for covalent immobilization of NADH in a soluble and enzymically active form.

Using a new and simplified technique for covalent immobilization of adenine nucleotides [Fuller, C. W. and Bright, H. J., J. Biol. Chem. 252, 6631 (1977)], we have prepared immobilized NADH using two water-soluble polymers and tested these preparations for activity with several dehydrogenases. The first polymer used, having a weight-average molecular weight of about 350000, is a copolymer of methacrylyl choline and the epoxide-containing monomer 3-[4-(2,3-epoxypropoxy)butoxy]-2-hydroxypropyl acrylate. Immobilization of NADH onto this copolymer was accomplished in three steps, namely, alkylation of NAD at N-1, reduction of the nicotinamide moiety with dithionite and Dimroth rearrangement of the alkyl linkage from the N-1 to the C-6 amino position. The second copolymer tested was a copolymer of the same epoxide-containing monomer and N-methacrylyl-2-glucosamine. Using this copolymer, immobilization of NADH through the adenine C-6 amino position was accomplished in a single step. Measurements of the steady-state kinetics of five dehydrogenases at pH 7 and pH 9 showed that, on the average, V and Km values obtained with the immobilized NADH were, respectively, about one third and twice those found for the free coenzyme. In general, when compared with the free coenzyme, the immobilized NADH had greater relative enzymic reactivity at pH 9 than at pH 7. The simplicity of this method, the general enzymic reactivity, and the ability to be recycled enzymically suggest that this immobilized NADH may be useful in creating enzyme reactors for synthetic, analytical and other purposes.

Acrylates↗

The nucleoside sequence of tyrosine tRNA from Bacillus stearothermophilus.

The nucleotide sequence of tRNATyr from B. stearothermophilus has been determined: pG-G-A-G-G-G-G-s4U-A-G-C-G-A-A-G-U-Gm-G-C-U-A-A-m1A-C-G-C-G-G-C-G-G-A-C-U-Q-U-A-ms2i6A-A-psi-C-C-G-C-U-C-C-C-U-U-U-G-G-G-U-U-C-G-G-C-G-G-T-psi-C-G-A-A-U-C-C-G-U-C-C-C-C-C-U-C-C-A-C-C-AOH. A combination of classical fingerprinting methods, partial nuclease P1 digestion and two-dimensional homochromatography and a rapid "read off" sequencing gel technique were used to establish the complete nucleotide sequence.

Base Sequence↗

Intralymphatic antibiotic delivery for reducing acute prosthetic graft infection.

The lymphatic system has been implicated as a source of synthetic graft contamination when grafts are implanted in the presence of a distal septic focus. In previous studies, radical lymphatic excision and ligation were shown to reduce acute graft sepsis. However significant lymphedema precluded its clinical application. The present study was undertaken to evaluate methods for reducing acute graft sepsis while avoiding lymphatic obstructive complications. Twenty dogs were divided into one control and two experimental cohorts. Femoral interposition grafts were placed in each dog. A hind paw septic focus was introduced and therapy included a control (Group I--no therapy), intravenous antibiotics in Group II and intralymphatic antibiotics in Group III. Graft, blood and tissue cultures from each dog were taken at 48 hours. Lymphatic antibiotic therapy resulted in significantly improved graft culture results when compared to the control (p = 0.0003) and intravenously treated animals (p = 0.007). Blood cultures in the intralymphatically treated group were also significantly better (p = 0.003) than the control group.

Animals↗