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K A Harris

Publications and source records attributed to K A Harris.

18 recordsLinked to original sources
PubMed1992

5-Chlorolevulinate modification of porphobilinogen synthase identifies a potential role for the catalytic zinc.

Porphobilinogen synthase (PBGS) is a Zn(II) metalloenzyme which catalyzes the asymmetric condensation of two molecules of 5-aminolevulinate (ALA). The nitrogen of the first substrate ends up in the pyrrole ring of product (P-side ALA); by contrast, the nitrogen of the second substrate molecule remains an amino group (A-side ALA). A reactive mimic of the substrate molecules, 5-chlorolevulinate (5-CLA), has been prepared and used as an active site directed irreversible inhibitor of PBGS. Native octameric PBGS binds eight substrate molecules and eight Zn(II) ions, with two types of sites for each ligand. As originally demonstrated by Seehra and Jordan [(1981) Eur. J. Biochem. 113, 435-446], 5-CLA inactivates the enzyme at the site where one of the two substrate molecules binds, and modification at four sites per octamer (one per active site) affords near-total inactivation. Here we report that 5-CLA-modified PBGS (5-CLA-PBGS) can bind up to four substrate molecules and four Zn(II) ions. Contrary to the conclusion of Seehra and Jordan, we find that the preferential site of 5-CLA inactivation is the A-side ALA binding site. On the basis of the dissociation constants, the metal ion binding sites lost upon 5-CLA modification are assigned to the four catalytic Zn(II) sites. 5-CLA-PBGS is shown to be modified at cysteine-223 on half of the subunits. We conclude that cysteine-223 is near the amino group of A-side ALA and propose that this cysteine is a ligand to the catalytic Zn(II). The vacant substrate binding site on 5-CLA-PBGS is that of P-side ALA. We have used 13C and 15N NMR to view [4-13C]ALA and [15N]ALA bound to 5-CLA-PBGS. The NMR results are nearly identical to those obtained previously for the enzyme-bound P-side Schiff base intermediate [Jaffe et al. (1990) Biochemistry 29, 8345-8350]. It appears that, in the absence of the catalytic Zn(II), 5-CLA-PBGS does not catalyze the condensation of the amino group of the P-side Schiff base intermediate with the C4 carbonyl derived from 5-CLA. On this basis we propose that Zn(II) plays an essential role in formation of the first bond between the two substrate molecules.

Amino Acid Sequence↗
PubMed1992

Graft infections.

Vascular graft infections are one of the most dreaded complications in vascular surgery. They may present a few months to many years following insertion of a bypass graft but are most prevalent in those patients with groin incisions. The most commonly infecting organism is Staphylococcus arising from the patient's skin. Presentation may be one of massive bleeding if one of the graft anastomoses is involved in the septic process (peri-anastomotic sepsis) or one of vague malaise and fever if the graft but not the anastomosis is involved (peri-graft sepsis). Once the diagnosis has been confirmed, treatment includes removal of the infected graft with reconstruction of the vascular system through one of a variety of methods. These controversies are discussed.

Blood Vessel Prosthesis↗
PubMed1992

Arteritis due to Salmonella with aneurysm formation: two cases.

Although arterial infection due to Salmonella is rare, it remains one of the most common causes of primary mycotic aneurysms. The presentation is one of sepsis, cultures positive for Salmonella and rapid expansion or rupture of the aneurysm. The authors' experience at Victoria Hospital, London, Ont., includes two cases of aneurysms infected with Salmonella--one aneurysm of the aorta and the other of the common femoral artery. Both patients were treated by excision of the aneurysm, extra-anatomic reconstruction in an area remote from the infected field and long-term administration of appropriate antibiotics. One patient was alive and well 36 months after resection. The other died of multiple organ failure 10 days after resection. From a review of the English and French literature since 1948, 64 cases of abdominal aortic aneurysms infected with Salmonella were found; half of the patients survived the perioperative period. The diagnosis of mycotic aneurysm must be considered in any patient with an aneurysm and culture specimens positive for Salmonella. The authors favour wide débridement of the infected aneurysm with extra-anatomic reconstruction. This view is supported by a review of the literature. The appropriate antibiotic therapy is bactericidal rather than bacteriostatic.

Aged↗
PubMed1992

The role of descending venography in the management of patients with chronic venous disease of the lower extremity.

The purpose of this paper is to evaluate the efficacy and clinical information obtained from the authors' first 17 consecutive descending venograms. All 17 patients had chronic venous disease refractory to standard conservative and surgical measures. The standard classification of valvular insufficiency was used in evaluating these venograms. There were no deaths, slight morbidity and minimal patient discomfort. In 16 patients meaningful clinical information was derived from the venograms, with 7 patients having deep venous valvular surgery. Descending venography will demonstrate the site of incompetent valves and estimate the degree of reflux. This test is necessary before anticipated reconstruction of deep vein valves.

Chronic Disease↗
PubMed1990

Management of venous stasis ulcer: long-term follow-up.

In this study 112 patients (122 lower limbs) who had chronic venous stasis ulceration refractory to conservative management were treated surgically. Subfascial ligation was performed on 118 limbs and the long saphenous vein was removed in 4. Complications consisted of postoperative thrombophlebitis (2%), wound infection (2%) and wound infection with ulcer necrosis (1.5%). These all responded to conservative management. Follow-up (mean 7.9 years, median 11 years) showed a good or excellent result in 82% of cases, with healing of the ulcer and no ulcer recurrence despite significant noncompliance with support stockings. This paper is a long-term follow-up study of a surgical procedure for chronic venous stasis ulcers. The authors believe that the 82% good and excellent results may indicate that surgical intervention for refractory venous ulcers is a worthwhile procedure, providing potentially satisfactory long-term results.

Follow-Up Studies↗
PubMed1990

Aneurysms of the inferior vena cava.

Aneurysms of the inferior vena cava are very rare. We describe a case of a saccular aneurysm of the inferior vena cava that thrombosed after vigorous exercise. This presented as deep venous thrombosis associated with a retroperitoneal mass. Laparotomy with biopsy confirmed the benign nature of this lesion, and symptoms gradually resolved. It is hypothesized that the increased intraabdominal pressure during exercise led to the thrombosis of what is presumed to be a congenital aneurysm of the inferior vena cava.

Adult↗
PubMed1989

External carotid-external carotid crossover anastomosis for reconstruction of common carotid resection.

A pilot project studying the feasibility of external carotid-external carotid cross-over anastomosis for reconstruction of common carotid artery resection is reported. Common carotid artery resection in the treatment of head and neck malignancy may be necessary when carcinoma involves the common carotid or when the common carotid artery ruptures. Ligation of the common carotid is associated with high mortality rates and high rates of neurologic complications. The vasculature to the internal carotid can be maintained by anastomosing both external carotid arteries across the midline. The diseased common carotid can then be ligated below the bifurcation. The crossover anastomosis was performed successfully in six cadaveric dissections with unilateral neck dissection and laryngectomy. Mobilizing the facial artery in conjunction with the external carotid artery provides added length. A large vessel anastomosis across the midline was performed in six sheep. Technical errors in two sheep resulted in obstruction. The remaining four anastomoses remained patent. The external carotid-external carotid crossover anastomosis may have application in the management of squamous cell carcinoma involving the common carotid or in the treatment of carotid artery blowout. Further study is warranted.

Anastomosis, Surgical↗
PubMed1989

Extra-anatomic bypass grafting: a rational approach.

To determine predictors of long-term patency in extra-anatomic bypass grafting, the authors studied retrospectively the charts of 134 patients who underwent bypass grafting (axillofemoral in 17, axillobifemoral in 32 and femorofemoral in 85). Of the study group, 64% were men; the mean age was 65 +/- 12 years (+/- SEM). The indications for grafting were limb salvage (102), claudication (27) and replacement of septic grafts (5), and for using the extra-anatomic route included high risk (83), sepsis (8) and unilateral disease (34). Operative mortality was 6% and the early graft occlusion rate 7.4%. The late death rate was 44%. At 3 years, the life-table patency rates for the various procedures were axillofemoral 52.5%, axillobifemoral 67.7% and crossfemoral 86.9%. Smoking significantly (p less than 0.05) decreased the patency rate, but diabetes did not. However, amputation was more frequent in diabetics. Indications for operation did not alter patency rates, but did affect operative mortality. The authors conclude that extra-anatomic bypass grafting is highly successful, but not as successful as anatomic bypass. When appropriate, the axillobifemoral graft is preferred to the axillounifemoral graft because of its increased patency. Crossfemoral grafts must be carefully monitored to ensure that no donor limb stenosis occurs and this procedure should not be attempted unless the disease is truly unilateral.

Adult↗
PubMedDate not supplied

A database coding system for vascular procedures.

A coding system was developed to overcome the difficulties encountered in data registry and retrieval from a national audit. In vascular surgery operations are frequently combined, and neither the OHIP fee schedule of codes (Ontario, Canada) nor the ICD-9 system provides sufficient detail for most vascular surgeons to retrieve information for long-term follow-up. However, some wish to record minimal data on their operative procedures. A numeric classification system was developed. A five-digit number is used, the first two digits classifying the operative procedure and anatomic details. Two decimal digits code the classification of operation (e.g., aortic aneurysm, tube graft, aortoiliac, or aortobifemoral) and the final digit may be used as a modifier. "Holes" in the numeric system allow for new operations to be added as they develop. Codes are stored in a database with the following fields: 1) codes; 2) description of operation; 3) translation. The translation field may be modified to permit translation of any existing databases into the system. This database has been distributed with a data registry program free of charge to vascular surgeons in Canada to allow nationwide registry of vascular surgery patients. A numeric code eliminates spelling and abbreviation errors, and can be sufficiently broad-based to allow all surgeons to participate in a nationwide audit.

Abstracting and Indexing↗
PubMedDate not supplied

Are simultaneous aortic reconstruction and renal revascularization safe and effective?

Between 1983 and 1989, 40 patients with uncontrollable hypertension underwent renal revascularization. Of these, 21 patients had simultaneous aortic and renal revascularization. Eleven of the 21 patients (52.4%) had renal insufficiency with a mean creatinine clearance of 0.61 +/- 0.23 ml/sec. Eleven patients had an aortic aneurysm; the remaining 10 patients had aortic occlusive disease of varying severity. Aortic reconstruction was done with either a straight (8 patients) or bifurcated (13 patients) Dacron graft. Renal revascularization was accomplished with either bypass (11 patients) or transaortic endarterectomy (10 patients). One patient died postoperatively secondary to myocardial infarction (operative mortality rate of 4.7%). Among the 11 patients with renal insufficiency the mean creatinine clearance of 0.61 +/- 0.23 ml/sec preoperatively improved to 0.94 +/- 0.30 ml/sec postoperatively (p less than 0.01). In the follow-up period extending to 78 months (mean 39.1 months), one late death occurred. There were no instances of worsening hypertension or deterioration in renal function. Contrary to some previous reports, our results indicate that severe aorto-renal atherosclerosis can be managed with simultaneous aortic reconstruction and renal revascularization at an acceptably low operative risk. In addition, a significant and persisting benefit in both hypertension control and renal dysfunction can be expected after surgery.

Aged↗
PubMedDate not supplied

Rehabilitation potential of elderly patients with major amputations.

This study was undertaken to determine the rehabilitation potential of patients undergoing amputation for vascular disease. A total of 101 patients were studied with a mean age of 69 +/- 14 years, 26 of whom were over age 80. Operative indications were gangrene or ulceration in 80% with rest pain in 20%. Eighteen patients were bilateral amputees. Fifty per cent of the patient population had previous vascular operations. The operative mortality was 13% and was not affected by the age of the patients or the presence of diabetes. Most operative deaths were due to cardiac or septic respiratory complications. Twenty-four of 88 surviving patients were not considered candidates for rehabilitation and the major determining factor was the occurrence of a remote or perioperative stroke. None of these 24 patients was discharged from institutional care. Sixty-four patients were considered rehabilitation candidates with equal distribution in all age groups. Ninety-five per cent of these patients were discharged home with 80% of those patients over 80 being discharged. Eighty-seven per cent of the elderly rehabilitation candidates were fitted with prostheses which compares favourably to other age groups. Seventy-three per cent of the elderly reached their rehabilitation goals (most frequently ambulation with the aid of a walker) which is only slightly less than the younger amputation group. From this study we conclude that amputations which are done for ease of nursing care and patient comfort in debilitated patients have a high mortality rate and rehabilitation goals are unlikely to be met. We have demonstrated high success rates with rehabilitation including patients over age 80. The majority of these patients may be discharged home after a period of aggressive rehabilitation.

Activities of Daily Living↗
PubMedDate not supplied

Angioscopy.

Over the past three to four decades vascular surgery has experienced increasing interest and rapid growth. This surgical specialty continues to show an annual increase in the number of procedures performed, and demonstrates increasing use of innovative technology. The author explains how the angioscope has emerged as a potentially powerful diagnostic tool for today's vascular surgeon. Its implications, complications and the post operative nursing care for the patient undergoing angioscopy will be discussed.

Angiography↗
PubMedDate not supplied

Confirmation of infection of an aortic graft.

The presentation of an aortic graft infection may be dramatic in the form of an aortoenteric fistula or drainage of pus from the wound. Some cases may be more subtle with presentations of fever of unknown origin. Prior to embarking upon major operative repair for these suspected lesions, it is essential to confirm the presence of infection. Under CT control, a fine needle may be inserted into the peri-graft space, and cultures may be obtained. Further confirmation may be achieved by an injection of a small amount of contrast material which will demonstrate lack of incorporation of the graft into surrounding tissues. Prior confirmation of graft infection permits a staged procedure to repair this technique is illustrated with a case history.

Aged↗