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Biomedical subjects

K A Myers

Publications and source records attributed to K A Myers.

At least 19 recordsLinked to original sources
PubMed1998

Improving the accuracy of death certification.

BACKGROUND: Population-based mortality statistics are derived from the information recorded on death certificates. This information is used for many important purposes, such as the development of public health programs and the allocation of health care resources. Although most physicians are confronted with the task of completing death certificates, many do not receive adequate training in this skill. Resulting inaccuracies in information undermine the quality of the data derived from death certificates. METHODS: An educational intervention was designed and implemented to improve internal medicine residents' accuracy in death certificate completion. A total of 229 death certificates (146 completed before and 83 completed after the intervention) were audited for major and minor errors, and the rates of errors before and after the intervention were compared. RESULTS: Major errors were identified on 32.9% of the death certificates completed before the intervention, a rate comparable to previously reported rates for internal medicine services in teaching hospitals. Following the intervention the major error rate decreased to 15.7% (p = 0.01). The reduction in the major error rate was accounted for by significant reductions in the rate of listing of mechanism of death without a legitimate underlying cause of death (15.8% v. 4.8%) (p = 0.01) and the rate of improper sequencing of death certificate information (15.8% v. 6.0%) (p = 0.03). INTERPRETATION: Errors are common in the completion of death certificates in the inpatient teaching hospital setting. The accuracy of death certification can be improved with the implementation of a simple educational intervention.

Bias↗
PubMed1997

Amino acid residues in both the DNA-binding and ligand-binding domains influence transcriptional activity of the human peroxisome proliferator-activated receptor alpha.

We have investigated the basis of the lack of activity of a natural variant human peroxisome proliferator-activated receptor alpha, hPPARalpha6/29. A subcloning approach was used to change the four variant amino acids in the hPPARalpha6/29 sequence, individually and in combination, to those found in an active human PPARalpha. Individual amino acid "back mutations" were unable to confer on hPPARalpha6/29 the ability to be activated by peroxisome proliferators in a transient transfection assay. Although hPPARalpha6/29 was able to bind specifically to DNA in the presence of the retinoid X receptor alpha (RXRalpha), the complete restoration of receptor transcriptional activity required two separate back mutations of the hPPARalpha6/29 sequence, namely amino acid 123 in the DNA binding domain, and amino acid 444 close to the C-terminus. This suggests that sequences in the PPARalpha DNA binding domain influence other receptor functions besides DNA binding.

Alanine↗
PubMed1996

Metastasis-associated 5T4 antigen disrupts cell-cell contacts and induces cellular motility in epithelial cells.

The 5T4 antigen is defined by a monoclonal antibody (MAb) specific for human trophoblast. It is also expressed by many types of tumour cell and has been associated with metastasis and poor clinical outcome in a number of cancers. This pattern of expression is consistent with a mechanistic involvement of 5T4 molecules in the spread of cancer cells. The 5T4 antigen is a transmembrane glycoprotein with a 310 amino acid extracellular domain and a 44 amino acid cytoplasmic domain. Transfection of full-length 5T4 cDNA into epithelial cells alters cell-cell contacts and cellular motility. Thus, in 5T4-transfected CL-S1 murine mammary cells, 5T4 expression is associated with dendritic morphology, accompanied by abrogation of actin/cadherin-containing contacts and increased motility. In transfected MDCK canine kidney epithelial cells, 5T4 over-expression also results in increased motility, but disruption of cell-cell contacts, either by culturing cells in low calcium medium or by addition of HGF/SF, is needed. The effects of 5T4 expression on morphology and motility are separable since cells transfected with a truncated form of 5T4 cDNA in which the cytoplasmic domain is deleted reveal that the latter is necessary to abrogate actin/cadherin-containing contacts but does not influence the effects on motility. Thus, 5T4 molecules can deliver signals through both the extracellular and intracellular domains, and the resultant effects are consistent with a role for 5T4 molecules in invasion processes.

Animals↗
PubMed1996

Clinical and vascular laboratory determinants for outcome after infrainguinal atherectomy.

Three surgeons performed 180 atherectomy procedures in 161 patients using the Transluminal Extraction Catheter in 144 and the Auth Rotablator in 36. The primary patency rate was 55% at 1 year and 46% at 2 years, and failure was caused by stenosis in 28 (15.6%) and occlusion in 61 (33.7%) limbs. Multivariate Cox regression analysis showed significantly better outcome if the indication was claudication, the lesion was short or there was associated stenting. Vascular laboratory surveillance was performed in 93 limbs in 83 patients. Cox regression analysis in this subgroup also showed a significant relationship between outcome and the maximum peak systolic velocity from a duplex scan at the last study performed. Receiver operating characteristics curves showed that a raised maximum peak systolic velocity best predicted late failure (sensitivity 84%, specificity 66% for > 200 cm/s; sensitivity 72%, specificity 84% for > 250 cm/s); the velocity ratio at the stenosis to that in the segment above or the resting ankle/brachial pressure index were less predictive. For 50 procedures studied in the vascular laboratory which remained successful to the end of the study, maximum peak systolic velocities were > 250 cm/s from the first postoperative study, suggesting residual stenosis in 6%, or increased to become > 250 cm/s by the last study, suggesting recurrent stenoses in 12%. For 43 procedures which were studied and later failed, velocities were > 250 cm/s from the first test in 26% or increased to > 250 cm/s by the last test before failure in 40%. Vascular laboratory surveillance helps to predict outcome after atherectomy. Failure may be a result of residual disease from the time of the procedure or from restenosis. The apparent high incidence of clinically manifest or developing stenoses raises doubts as to the benefit of atherectomy over balloon dilatation alone.

Adult↗
PubMed1995

Duplex ultrasonography scanning for chronic venous disease: patterns of venous reflux.

PURPOSE: Patterns of flow in superficial and deep veins and outward flow in medial calf perforators were studied by duplex ultrasonography scanning in 1653 lower limbs in 1114 consecutive patients. This study compares results in 776 limbs with primary uncomplicated varicose veins with those in 166 limbs with the complications of lipodermatosclerosis or past venous ulceration. METHODS: Duplex scanning determined whether superficial and deep veins were occluded or showed reflux and whether outward flow occurred in medial calf perforators with calf muscle contraction. RESULTS: Two proximal deep veins were occluded. When limbs with primary uncomplicated varicose veins, lipodermatosclerosis, or past ulceration were compared, superficial reflux alone was seen in 55%, 39%, and 38%, deep reflux alone was seen in 2%, 7%, and 8%, and combined superficial and deep reflux was seen in 18%, 34%, and 48%, respectively. Superficial reflux affected the long saphenous system alone in 58%, 57%, and 40%, the short saphenous system alone in 18%, 18%, and 26%, and both the long and short saphenous systems in 24%, 25%, and 34%, respectively. Limbs with ulceration more frequently showed superficial reflux (p < 0.05), and all limbs with complications more frequently showed short saphenous reflux (p < 0.05) and deep reflux (p < 0.01) specifically in the posterior tibial veins (p < 0.01). Outward flow was seen in medial calf perforators in 57%, 67%, and 66%, respectively; it occurred more frequently in all limbs with complications (p < 0.05). Isolated outward flow in perforators without superficial or deep reflux was seen in 10%, 10%, and 2%, respectively. CONCLUSIONS: Most limbs with complications had superficial reflux either alone or combined with deep reflux, and few had deep reflux alone. Reflux was more frequent in posterior tibial veins for limbs with complications compared with those with uncomplicated primary varicose veins. Outward flow in perforators was common in limbs with complications and with uncomplicated primary varicose veins, but isolated outward flow in perforators was uncommon. Treatment directed to the superficial veins alone may be sufficient for most patients with complications.

Chronic Disease↗
PubMed1995

Metastasis-associated 5T4 oncofoetal antigen is concentrated at microvillus projections of the plasma membrane.

The 5T4 oncofoetal antigen is a 72 kDa glycoprotein defined by a monoclonal antibody raised against human placental trophoblast and is expressed in many different carcinomas but detected only at low levels in some normal epithelia. Immunohistochemical analysis of the patterns of expression in colorectal carcinomas has indicated a significant association between the presence of the antigen in tumour cells and metastatic spread. A cDNA encoding the 5T4 molecules has been isolated and the extracellular portion contains several leucine-rich repeats which have been implicated in cellular interactions. To study the cell biological role of 5T4 molecules, murine L cells (A9 derivative) were stably transfected with 5T4 cDNA under the control of the CMV immediate-early promoter. The 5T4-expressing cells exhibited a more spindle-shaped morphology compared to the vector alone transfected cells. Confocal immunofluorescence microscopy revealed a 'polkadot' pattern of 5T4 antigen expression, heterogeneous in intensity between cells, but distributed over the entire cell surface. Transmission and scanning electron microscopy showed that the 5T4 antigen is concentrated at microvillus projections of the plasma membrane both in the transfected A9 cells and in various carcinoma cell lines. Such projections express an array of surface molecules which function in cell adhesion and motility. This association of 5T4 antigen with microvillus projections was also observed in various carcinoma cell lines. 5T4 expression in A9 cells was also associated with an altered pattern of cell division, decreased cell-substratum adhesion and increased cellular motility. These results support the hypothesis that 5T4 molecules may have a direct function in trophoblast and tumour cell invasion processes.

3T3 Cells↗
PubMed1995

Infrainguinal atherectomy using the Auth Rotablator: patency rates and clinical success for 36 procedures.

PURPOSE: To determine whether the Auth Rotablator device is suitable for endoluminal atherectomy for infrainguinal occlusive arterial disease. METHODS: Two surgeons used the Auth Rotablator to perform 36 infrainguinal atherectomy procedures in 34 patients for severe intermittent claudication in 21, critical ischemia in 12, or graft stenosis in 3 limbs. There were 24 stenoses and 12 occlusions. Adjuvant balloon dilation was performed in 13 limbs and stenting in 5. RESULTS: There was initial technical and anatomical success in 34 procedures (94%), and 24 technically successful procedures persisted at mean follow-up of 16.5 months, although 1 limb required major amputation. Three failures were due to stenosis requiring further intervention, and 9 were due to occlusion. Failure led to no further intervention in 2, amputation in 1, further endovascular intervention in 5, and open surgical reconstruction in 4 limbs. After further treatment, 29 limbs are patent with no return of symptoms, 3 are occluded, and 4 have required amputation, all for initial presentation with critical ischemia. Life-table analyses calculate primary and secondary patency rates of 61% and 67% and a clinical success rate of 56% at 12 months. CONCLUSIONS: Atherectomy using the Auth Rotablator provides acceptable results, but its role in comparison to other endovascular techniques is still to be defined.

Aged↗
PubMed1994

Isolation of a cDNA encoding 5T4 oncofetal trophoblast glycoprotein. An antigen associated with metastasis contains leucine-rich repeats.

The monoclonal antibody 5T4 defines a human oncotrophoblast antigen expressed by a variety of carcinomas but with a restricted pattern of expression in normal adult tissues. The 5T4 antigen has been isolated from term placenta as a 72-kDa glycoprotein consisting of a 42-kDa core protein with extensive N-linked glycosylation. A cDNA has been isolated from a human placental library using pools of oligonucleotides based on amino acid sequence obtained from purified 5T4 molecules. The predicted open reading frame encodes a protein of 420 amino acids with a molecular mass of 46 kDa and 8 potential N-glycosylation sites. There are N- and C-terminal hydrophobic segments corresponding to putative signal and membrane anchorage sequences, respectively. Northern analysis has demonstrated a major 2.5-kilobase mRNA present in cell lines serologically reactive with the monoclonal antibody 5T4. Comparison of the 5T4 protein sequence with current sequence data bases has identified the presence of leucine-rich repeats, which are found in a variety of proteins from yeast, insects, and mammals. The 5T4 antigen expression is strongly associated with metastasis in colorectal and gastric cancer, and, hence, the possible functions of the gene product and its relationship to tumor growth and progression are discussed.

Amino Acid Sequence↗
PubMed1994

Prognostic significance of 5T4 oncofetal antigen expression in colorectal carcinoma.

The 5T4 oncofetal antigen is a 72 kDa glycoprotein defined by a monoclonal antibody raised against human placental trophoblast and is expressed in many different carcinomas but detected only at low levels in some normal epithelia. Immunohistochemical analysis of the patterns of expression in colorectal carcinomas has indicated a significant association between the presence of the antigen in tumour cells and metastatic spread. The 5T4 antigen phenotype of 72 colorectal cancers has been compared with the clinical outcome of the patients in order to assess its relationship with prognosis. Forty per cent of tumours were 5T4 positive; the remainder were either unlabelled or exhibited stroma-associated labelling only. There was a significant correlation between 5T4 expression in the malignant cells and unfavourable course of disease (P < 0.001). The 5 year survival with 5T4-positive tumours was 22% compared with 75% for patients with 5T4-negative tumours; median survival was 24 versus > 90 months respectively. Stratified analysis showed that 5T4 antigen tumour positivity was acting independently of each of stage, site of tumour, age or sex. There were significant differences in survival for patients with Dukes' B and C stage carcinomas (P = 0.001 and P = 0.034). The results suggest that in colorectal cancer immunohistochemical assessment of 5T4 expression may be useful in identifying patients at high risk for tumour recurrence and for whom additional treatment strategies might be most appropriate.

Adult↗
PubMed1994

Infrainguinal atherectomy using the transluminal endarterectomy catheter: patency rates and clinical success for 144 procedures.

PURPOSE: To determine if atherectomy using the transluminal endarterectomy catheter (TEC) is an effective endoluminal therapy for infrainguinal occlusive disease. METHODS: Three surgeons used the TEC for 144 infrainguinal atherectomy procedures in 133 patients. The indications were severe claudication in 83, critical ischemia in 56, and graft stenosis in 5 limbs. The pathology was stenosis in 36 and occlusion in 105 limbs. Balloon dilation was also performed in 109 and stenting in 17 limbs. RESULTS: There was initial technical and anatomic success in 124 (86%) procedures. There were 67 technically successful procedures at mean follow-up of 19 months, although 3 of these limbs with gangrene and extensive distal disease required major amputation. There were 26 failures due to stenosis leading to further intervention and 51 due to occlusion. Twenty of these cases were managed conservatively, 21 were treated with repeat endovascular intervention, 31 with bypass grafting, and 5 with amputation. Repeat intervention in 52 limbs resulted in 36 with patent arteries, 10 that are occluded, and 6 that required amputation. Thirteen of the 14 amputations were for limbs with critical ischemia, but 1 was in a patient with claudication. Life-table analysis showed that the primary patency rate was 51%, the assisted primary patency rate was 61%, and the secondary patency rate was 75% at 15 months. The clinical success rate was 49%, and the salvage rate for limbs with critical ischemia was 78% at 12 months. Univariate log-rank testing showing no significant differences according to the clinical presentation of pathology, but results were worse for lesions > 5 cm long due to more frequent immediate failures. However, multivariate Cox regression analysis showed that results were significantly worse for critical ischemia than for claudication, stenosis compared to occlusions, for limbs with poor runoff, for operations performed by percutaneous rather than an open approach, and for those performed more recently. CONCLUSIONS: TEC atherectomy may have a place in selected patients, but the optimal circumstances for its use and long-term efficacy require further study.

Adult↗
PubMed1994

Perioperative stroke after carotid endarterectomy. Etiological risk factors and management.

291 patients were subjected to carotid endarterectomy from January 1985 to June 1992 in two Australian medical institutions. Of the 291 patients, perioperative stroke occurred in 22 (6.3%) after 347 operations (moderate 17 and severe 5). The 22 patients were studied with Doppler scan, angiography, reexploration and CT. Reexploration showed that 12 of 14 patients had thrombosis in the internal carotid artery at operation. The etiological factors for perioperative strokes included thrombosis at the operative sites in 14 patients (64%), cerebral embolism after operation in 4, clamping ischemia in 2, intracerebral hemorrhage in 1 and unknown cause in 1. Six patients (27%) recovered completely in 4 weeks, 10 (45%) had mild residual neurological deficits, 5 (23%) had moderate neurological deficits and 1 died 3 days after operation. Only 6 patients had permanent neurological deficits (6/347, 17%).

Aged↗
PubMed1993

Multivariate Cox regression analysis of covariates for patency rates after femorodistal vein bypass grafting.

Multivariate Cox regression analysis of patency rates for 750 consecutive femorodistal autogenous vein graftings for chronic lower limb ischemia showed that significant independent prognostic covariates were the type of graft (long saphenous or arm vein), presence of diabetes, and absence of a past history of myocardial ischemia. Analysis assumes that patients withdrawn with patent grafts due to death or loss to follow-up would have followed the same course as those who remain, and the degree to which this could distort results was studied. Patients who died with patent grafts were more likely to have had past myocardial ischemia and critical lower limb ischemia. Cox regression analysis for 600 operations after excluding patients who died with patent grafts then showed that significant independent covariates were the type of graft (long saphenous or arm vein) and indication (claudication or critical ischemia); then age, sex, hypertension, diabetes, myocardial ischemia, date of operation, surgeon, site of distal anastomosis, or first compared to repeat operations had no significant influence. Cox regression analysis helps determine which covariates influence graft patency rates, but results are affected by censored data, particularly from patients who die with patent grafts.

Adult↗