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Biomedical subjects

K A Harris

Publications and source records attributed to K A Harris.

At least 19 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↗
PubMed1988

A simplified method of performing patch angioplasty for profunda femoris origin stenosis.

A simplified method of performing an autogenous profundoplasty is described using the partially detached and open superficial femoral artery as a patch. This permits better visibility while performing the anastomosis since the superficial femoral artery is no longer obstructing the view, which also allows easy access to any bleeding following clamp removal.

Blood Vessel Prosthesis↗
PubMed1988

Simple method of intraoperative blood collection and reinfusion during aortic surgery.

The increasing fear of acquired immune deficiency syndrome and other blood-transmissible diseases and increasing blood-bank shortages prompted a study of the safety and feasibility of a commercially available hand-held unit for collecting and reinfusing blood. The device was used on nine patients undergoing aortic surgery and permitted a mean saving of 2.6 units of banked blood. The reinfusion of collected blood did not result in any coagulation disturbances or changes in renal function. The hemoglobin and platelet levels were comparable to those in a group of patients receiving only banked blood. The unit does not require additional personnel or technical training for its use. The authors conclude that this autotransfusion device is a safe and feasible method of reducing the requirement for banked blood during aortic surgery.

Aorta↗
PubMed1987

Physiological response to circuit weight training in borderline hypertensive subjects.

Male subjects (10 experimental, 16 control) with borderline hypertension (140/90 to 160/95 mm Hg) participated in a circuit weight training program for 9 wk to assess its efficacy and safety. Resting blood pressure and heart rate were measured under standardized conditions prior to and following each session and at several locations in the circuit. Subjects were assessed pre- and post-training. Upper and lower body strength increased 12.5 and 53% when assessed by one-repetition maximum lifts for bench press (57 to 64 kg) and leg press (134 to 205 kg), respectively. Total weight lifted per circuit increased 57% (4,374 to 6,866 kg). Lean body mass increased 2.2% (64.0 to 65.4 kg), skinfold thicknesses decreased, and other measures of body composition remained unchanged. Cardiovascular endurance as assessed by arm ergometry maximal oxygen uptake increased 21.1% (1.9 to 2.3 1 X min-1), and by 7.8% as assessed by treadmill maximal oxygen uptake (40.9 to 44.1 ml X kg-1 X min-1). Resting heart rate and systolic blood pressure did not change. Diastolic blood pressure fell from 95.8 to 91.3 mm Hg. All changes were significant to at least P less than 0.05. Thus, circuit weight training can elicit marked improvements in muscular strength and modest improvements in body composition and cardiorespiratory endurance. Circuit weight training does not exacerbate resting or exercise blood pressure and may have beneficial effects.

Adult↗
PubMed1987

A single treadmill exercise test does not accurately quantitate claudication.

The diagnosis of vascular occlusive disease is confirmed by documenting a fall in the ankle-brachial pressure index following a treadmill exercise test. The authors hypothesize that this test does not provide a reproducible quantitative assessment of the patient's disability due to the disease. In 25 patients a series of five treadmill exercise tests were performed on the same day. There was a significant (p less than 0.05) increase in the time to the occurrence of claudication when tests 3, 4 and 5 were compared with test 1. There was also a significant (p less than 0.05) rise in the maximum time walked comparing test 3 with test 1. There was no difference in the fall in ankle-brachial pressure index with each test. The majority of patients had achieved their maximum walking distance by test no. 3. It is concluded that a single treadmill exercise test will not accurately assess disability due to intermittent claudication and it is recommended that three tests be performed for a reproducible evaluation.

Blood Pressure↗
PubMed1986

Abdominal aortic aneurysm resection in patients more than 80 years old.

Improvement in anesthetic and surgical techniques has prompted a more aggressive approach to repair of abdominal aortic aneurysms in patients more than 80 years old. In order to determine if surgical treatment is justified, all of the patients who were more than 80 years old admitted to the hospital during the ten year period from 1974 to 1983 with the diagnosis of abdominal aortic aneurysm were reviewed. A total of 90 patients were available for analysis. The mortality of the 18 patients treated conservatively for ruptured aortic aneurysms was 100 per cent. Ten of the 27 patients operated upon for a ruptured aneurysm died yielding a mortality of 37 per cent. Eleven patients with symptomatic aneurysms had urgent repair with a mortality of 27 per cent. Only one of the 34 patients undergoing elective aneurysm repair died. There was no difference in the size of aneurysms among the groups. Although the ruptured aneurysms required more blood (10.2 +/- 3.7 units), there was no difference between the other two groups (symptomatic 4.5 +/- 3.1 units, elective 4.6 +/- 2.8 units). There was significantly fewer myocardial and renal complications in the elective group, although the sole death in this group was from myocardial infarction. Based upon these observations, we recommend aggressive elective therapy for selected patients who are more than 80 years of age with asymptomatic abdominal aortic aneurysms. Although the mortality is higher in those patients with symptomatic or ruptured aneurysms, it is not formidable, and therefore, repair should not be ruled out on the basis of age alone.

Aged↗