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Biomedical subjects

W K Nichols

Publications and source records attributed to W K Nichols.

At least 19 recordsLinked to original sources
PubMed1999

The role of heparin-associated antiplatelet antibodies in the outcome of arterial reconstruction.

PURPOSE: This study was designed to determine the incidence rate of heparin-associated antiplatelet antibodies (HAAb) in patients who require major vascular reconstruction and to determine whether the HAAb were associated with perioperative thrombotic events. METHODS: One hundred six patients who underwent elective arterial reconstruction for cerebrovascular occlusive disease (n = 48), aortoiliac occlusive disease (n = 13), aortoiliac aneurysm (n = 17), mesenteric arterial occlusive disease (n = 1), or infrainguinal arterial occlusive disease (n = 28) prospectively underwent evaluation from July 1, 1996, to June 30, 1997. Heparin-associated antibody tests (with a two-point platelet aggregation assay) and platelet counts (via Coulter counter) were performed before surgery and on or after the 4th day after vascular reconstruction. Arterial reconstruction thromboses were established by means of duplex ultrasound scanning or angiography. Acute myocardial infarction (AMI) and venous thromboses were diagnosed with clinical criteria and duplex ultrasound scanning, respectively. A significant decrease in platelet count was defined as a platelet count of less than 100, 000/mm3 or as a more than 30% drop in the platelet count. RESULTS: Twenty-two patients (21%) had at least one positive HAAb assay: one assay was positive before surgery only (after angiography), six were positive both before and after surgery, and 15 were positive after surgery only. There were three perioperative deaths-one in the HAAb-positive group and two in the HAAb-negative group. Ten thrombotic events occurred in the perioperative period. Four thrombotic events (three operative site thromboses and one AMI) occurred in the HAAb-positive group (18.2%). All of these patients were undergoing heparin therapy. Of the six patients (with three operative site thromboses, two deep venous thromboses, and one AMI) in the HAAb-negative group (7%; P =.21), three were undergoing heparin therapy. No patient who was HAAb positive with a thrombotic event had thrombocytopenia or a significant decrease in platelet count. CONCLUSION: The frequent exposure to heparin by patients with peripheral vascular disease is associated with a high incidence rate (21%) of HAAb formation, which makes it one of the more common hypercoagulable conditions in these patients. The patients who were HAAb positive had a 2.6-fold increase in perioperative thrombotic events. Thrombocytopenia or decreasing platelet counts were not reliable clinical markers for identifying patients who were HAAb positive. It is suggested that all patients who have undergone heparin therapy and who have an unexplained perioperative thrombotic event develop should undergo testing for HAAb.

Antibody Formation↗
PubMed1996

Four-year experience with swan neck presternal peritoneal dialysis catheter.

The swan neck presternal catheter is composed of two flexible (silicon rubber) tubes joined by a titanium connector at the time of implantation. The exit site is located in the presternal or parasternal area. The catheter located on the chest was designed to reduce the incidence of exit site infections compared with peritoneal dialysis catheters with abdominal exit sites. From August 1991 to May 1995, 24 swan neck presternal catheters have been implanted in 24 patients for the following reasons: obesity nine patients, ostomies three patients, a suprapubic catheter one patient, previous problems with abdominal catheters two patients, desire to use a bathtub five patients, need to use a whirlpool one patient, need to wear sweatpants with an elastic waistband one patient, and body image two patients. In the same period, 47 abdominal swan neck catheters were implanted in 44 patients who preferred catheters with the exit on the abdomen. Presternal catheters tended to perform better regarding exit and tunnel infections, even though they were implanted in several patients in whom regular catheters with the exit on the abdomen would be difficult or impossible to implant. Two-year survival probability of presternal catheters was 0.88 +/- 0.14 (+/- SE). Recurrent/refractory peritonitis was the only reason of catheter failure. The differences in results between presternal and abdominal catheters were statistically insignificant; only the use of antibiotics to treat exit site infection was significantly higher with abdominal catheters. Patient acceptance of the exit position was good; at least seven patients preferred presternal catheter for psychological or body image reasons. We conclude that the swan neck presternal catheters provide excellent results comparable to those achieved with swan neck abdominal catheters. The catheter seems suitable for any patient commencing peritoneal dialysis and is particularly useful in extremely obese patients (body mass index > 40 kg/m2) and those with ostomies. The catheter exit location in the chest may be preferred by some patients, both men and women, for psychological or body image reasons. No specific contraindications to the presternal catheter implantation have been identified.

Abdomen↗
PubMed1995

Oxidation at C-1 controls the cytotoxicity of 1,1-dichloro-2,2- bis(p-chlorophenyl)ethane by rabbit and human lung cells.

Isolated rabbit Clara cells and a transformed human bronchial epithelial cell line, BEAS-2B, were used to investigate the mechanism of cytotoxicity of 1,1-dichloro-2,2-bis(p-chlorophenyl)ethane (DDD), a persistent insecticide and stable metabolite of 1,1,1-trichloro-2,2- bis(p-chlorophenyl)ethane. Both BEAS-2B cells and rabbit Clara cells were highly susceptible to DDD toxicity and were partially protected by 1-aminobenzotriazole, a suicide substrate inhibitor of cytochrome P450 enzymes. DDD (0.05 mM) killed 47 +/- 1.8% of rabbit Clara cells and 42 +/- 7.9% of BEAS-2B cells after 3 hr and 84 +/- 3.0% of rabbit Clara cells and 80 +/- 14% of BEAS-2B cells after 6 hr. Consequently, DDD is the most potent Clara cell toxicant recognized to date. The cytotoxicity of DDD to these cells was decreased by deuterium substitution at the C-1 position. Rabbit Clara cells and pulmonary microsomes incubated with 14C-DDD produced the fully oxidized acetic acid metabolite 2,2'-bis(p- chlorophenyl)acetic acid (DDA), but DDA was not formed by Clara cells when DDD was coincubated with 1-aminobenzotriazole. These results support the hypothesis that the cytotoxicity of DDD to susceptible subpopulations of rabbit and human lung cells is, at least in part, caused by cytochrome P450-mediated oxidation of DDD at C-1. A required step for the production of the cytotoxic intermediate is proposed to be the formation of a highly reactive acyl halide intermediate that is readily hydrolyzed to a stable, nontoxic metabolite, DDA.

Animals↗
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↗
PubMed1993

Metabolism and bioactivation of 3-methylindole by Clara cells, alveolar macrophages, and subcellular fractions from rabbit lungs.

3-Methylindole (3MI), a fermentation product of tryptophan produced by intestinal and ruminal microflora, has been shown to cause pneumotoxicity in several species subsequent to cytochrome P450-mediated biotransformation. Among several species studied, rabbits are comparatively resistant to 3MI-induced pneumotoxicity, especially when compared to goats or mice. In this study, rabbit pulmonary cells and subcellular fractions were used to examine the metabolism and bioactivation of 3MI. A covalent-binding metabolite was produced in 3MI incubations by both Clara cells and macrophages. The addition of the cytochrome P450 inhibitor, 1-aminobenzotriazole, to these incubations inhibited the production of covalent-binding metabolite(s) by 94% in Clara cells and only 24% in macrophages. In incubations of Clara cells or macrophages with 3MI and N-acetylcysteine (NAC), a polar conjugate was detected and tentatively identified as an adduct of 3-hydroxy-3-methylindolenine (3H3MIN). Also identified were 3[(N-glutathione-S-yl)-methyl]-indole (3MI-GSH) and 3-methyloxindole (3MOI). In rabbit lung microsomal incubations with 3MI and glutathione (GSH), 3MI-GSH, 3MOI, indole-3-carbinol, and a GSH adduct of 3H3MIN were identified. The addition of cytosol to the microsomal incubations with GSH did not increase the rate of formation of the GSH adducts, indicating that cytosolic GSH-S-transferases are not essential in the formation of these metabolites. GSH significantly decreased the covalent binding of an electrophilic metabolite in microsomal incubations. These data suggest that GSH may be important in the mitigation of 3MI toxicity. Furthermore, the comparison of 3MI bioactivation to electrophilic intermediates in Clara cells and alveolar macrophages suggests that 3MI is metabolized by different oxidative pathways in the two different cell types, although the same metabolites were produced by the two cell types. This study shows that rabbit pulmonary enzymes are capable of bioactivating 3MI to reactive intermediates which become covalently bound to cellular macromolecules. This indicates that the relative resistance of rabbits to 3MI-induced pneumotoxicity is probably not due to differences in metabolic enzymes which convert 3MI to reactive intermediates.

Acetylcysteine↗
PubMed1993

Swan neck presternal peritoneal dialysis catheter.

We hypothesized that a swan neck catheter for peritoneal dialysis with the exit in the presternal area will be less likely to develop an exit-site infection than currently used peritoneal dialysis catheters with the exit located on the abdomen. The chest is a sturdy structure with minimal wall motions; the catheter exit located on the chest wall is subjected to minimal movements decreasing the chances for trauma and contamination. Also, in patients with abdominal ostomies and in children with diapers, a chest exit location will decrease chances of contamination. The presternal peritoneal dialysis catheter is composed of two flexible (silicone rubber) tubes joined through a titanium connector at the time of implantation. Four such catheters were implanted in four patients: two in extremely obese patients, one in a patient with a suprapubic catheter, and one in a patient with a chronic exit infection with a previous catheter. Tensile strength tests showed that the two parts of the catheter practically cannot separate spontaneously in the tunnel. Flow rates were adequate in the supine and sitting positions. All catheters functioned and healed well, and the exits have not become infected during the whole observation period up to 11 months. These preliminary experiences support the rationale of catheter design.

Catheterization↗
PubMed1993

Peritoneal catheters and exit-site practices: toward optimum peritoneal access.

The peritoneal catheter is the CAPD patient's lifeline. Advances in catheter knowledge have made it possible to access the peritoneal cavity safely and maintain access over an extended period of time. Infection at the exit site remains a major problem, a solution for which is being extensively researched. The successful outcome of a catheter in an individual depends on meticulous care and adherence to sound principles of catheter insertion and management. The guidelines provided in this publication represent the consensus based on the extensive experience of several major centers worldwide.

Catheters, Indwelling↗
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↗
PubMed1992

Bioactivation of halogenated hydrocarbons by rabbit pulmonary cells.

1,1-Dichloro-2,2-bis (4'-chlorophenyl)ethane (DDD), 1,2-dibromoethane (DBE) and trichloroethylene are three halogenated hydrocarbons that selectively bind to pulmonary epithelial cells and that may be pneumotoxic. The susceptibility of pulmonary cells and the mechanisms of cytotoxicity of these compounds were evaluated using enriched subpopulations of isolated rabbit lung cells incubated with DDD, DBE, and trichloroethylene. These chlorinated and brominated hydrocarbons were studied to evaluate their ability to induce selective pneumotoxicity by their bioactivation in three cell types, i.e. Clara cells, alveolar type II cells, and alveolar macrophages. Evidence of cytochrome P-450 bioactivation was assessed by utilizing the suicide inhibitor, 1-aminobenzotriazole (ABT) to ameliorate cytotoxicity. DDD, DBE and trichloroethylene were cytotoxic to Clara cells, type II cells and alveolar macrophages and the order of cell susceptibility to DDD was Clara > type II > macrophages. DBE and trichloroethylene were nonselectively cytotoxic. ABT reduced the cytotoxic effects of DDD and DBE in Clara cells. These studies indicated that all three compounds were toxic to isolated lung cells and that bioactivation of DDD and DBE in rabbit Clara cells to a cytotoxic intermediate was mediated, at least in part, by cytochrome P-450 oxidation.

Animals↗
PubMed1992

Swan neck presternal ("bath tub") catheter for peritoneal dialysis.

We hypothesize that the swan neck catheter for peritoneal dialysis with exit in the presternal area will have better exit site healing and a decreased incidence of exit site infection than currently used peritoneal dialysis catheters with the exit located on the abdomen. The chest is a very stable structure, with minimal wall motion, especially of the upper chest and over the sternum. Hence, a catheter exit located on the chest will be subjected to only minimal movement. Decreased piston like movement of the catheter at the exit site reduces inward transfer of outer microbial flora. Moreover, a tight garment is usually not worn on the chest and there is less pressure on the exit. Based on this rationale a new catheter (swan neck presternal) has been designed. The presternal peritoneal dialysis catheter is composed of two flexible (silicon rubber) tubes joined through a titanium connector at the time of implantation. The device has been dubbed as a "bath tube" catheter because, with the exit on the chest, a patient may take a tub bath without the risk of exit contamination due to submersion. Two such catheters were implanted in two patients. One patient had multiple problems (including chronic exit site infection) with a previously implanted swan neck Missouri 2 catheter, the other patient was originally rejected as a peritoneal dialysis candidate due to extreme obesity. Both catheters healed well in 6 weeks and the exits have not become infected during the first 8 months. These preliminary experiences with 2 catheters support the rationale of their design.

Catheters, Indwelling↗
PubMed1992

Six-year experience with swan neck catheters.

From the beginning of our continuous ambulatory peritoneal dialysis (CAPD) program in January 1977 until June 1985, we used Tenckhoff and Toronto Western Hospital catheters. Throughout these years catheter survival probabilities of about 30% at three years persisted unchanged and were similar to survival probabilities reported by the National CAPD Registry special survey for these catheters. The first improvement in catheter results regarding leaks was noted after the adoption of lateral catheter insertion. Malfunction was less using swan neck prototypes from August 1985 to April 1986. The latter catheters were made of 80 degrees arc angle tubing between 8.5 cm spaced cuffs and were inserted in a reversed U-shape tunnel with the incision at the top of the tunnel. The use of these catheters was abandoned because of high cuff extrusion and exit infection rates. The next generation of swan neck catheters, the swan neck Missouri 2 and 3 catheters with straight intraperitoneal segments, improved the results dramatically. These catheters were made of 180 degrees arc angle tubing between 5 or 3 cm spaced cuffs. The estimated survival probability of 61% at three years more than doubled compared to previously used catheters. Recently we modified the intraperitoneal segment of the catheters, replacing the straight segment with a coiled one. These modified catheters, the swan neck Missouri coiled catheters, have been used exclusively since February 1990. In addition to an acceptable survival probability of 88% at one year, there are two major advantages of these catheters, the same as for other coiled catheters: elimination of infusion pain due to a jet effect and pain related to straight catheter tip pressure on the peritoneum experienced by some patients.

Bacterial Infections↗
PubMed1992

Isolated traumatic accessory splenic rupture: a case report and literature review.

Although small and relatively protected, an accessory spleen can be the cause of acute intraabdominal symptoms following minimal trauma. Although a splenic fracture or laceration may not be apparent on by CT scan, the scan cannot rule out the possibility. The diagnosis of splenic injury should be entertained in light of appropriate history and physical findings. The case we present and prior similar cases are a useful review of isolated accessory splenic rupture due to blunt trauma.

Abdominal Injuries↗
PubMed1991

Morphology of peritoneal dialysis catheter tunnel: macroscopy and light microscopy.

There is scanty knowledge of the morphology of peritoneal dialysis catheter tunnels in humans, even though such knowledge may impact on peritoneal catheter design, implantation and postimplantation care. Past descriptions of catheter tunnels are based mainly on data from animal experiments. Based on these data, it has been assumed that epidermal spreading is inhibited by collagen fibers ingrown into the cuff. Our preliminary investigation indicated that this may not be the case in humans and led us to study catheter tunnel morphology in more detail. Eighteen catheter tunnels (2-5mm of tissue around the catheters) were removed in 17 peritoneal dialysis patients. The catheters were inserted 30 to 2013 days prior to removal (median 366 days). The catheters were removed electively or because of infectious or noninfectious complications. Contrary to the observations in animals, in only 1 case did epithelium extend to the cuff with only a minimal amount of granulation tissue present at the end of a 9 mm long sinus tract. In the remaining cases, the leading edge of the epithelium always met granulation tissue 1-14 mm from the exit, and the cuffs were found 8-33 mm from the exit. In tunnels older than 197 days, dense fibrous tissue was ingrown into the cuffs, and a dense fibrous capsule surrounded the cuff. The uninfected intercuff segment formed a pseudosheath, indistinguishable from a tendon sheath or synovial membrane. Infection in the catheter tunnel propagates through the part of the cuff adjacent to the tubing inside the capsule, suggesting that the cuff per se does not constitute a major barrier for spreading infection. This observation, by exclusion, infers that the beneficial role of an external cuff in decreasing exit infections is by providing firm anchorage of the catheter resulting in restriction of its piston like movement and thereby minimizing trauma and inward conveyance of outer sinus tract flora.

Adolescent↗
PubMed1991

Complete external iliac artery disruption after percutaneous aortic valvuloplasty in two young children: successful repair with hypogastric artery transposition.

The majority of vascular injuries in young children are iatrogenic. This is a report of two complete external iliac artery disruptions occurring during percutaneous transfemoral balloon aortic valvuloplasty in a 2-year-old and a 5-year-old child. The damaged external iliac artery was bypassed by extensively mobilizing the hypogastric surgery and rotating it upward to anastomose it to the proximal common femoral artery. Normal limb pulses, function, and growth were noted in follow-up.

Anastomosis, Surgical↗