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Biomedical subjects

K A Williams

Publications and source records attributed to K A Williams.

At least 73 records · Page 4Linked to original sources
PubMed1995

The role of scintigraphic perfusion imaging for predicting ischemic cardiac events in noncardiac surgery.

The prediction of perioperative cardiac events remains a challenging issue in clinical cardiology. The most important cause of perioperative cardiac morbidity and death continues to be myocardial infarction, which is associated with a high prevalence of occult coronary artery disease. A large amount of data substantiates the validity of scintigraphic perfusion imaging for accurate diagnosis of coronary artery disease, as well as the prediction of prognosis in stable coronary disease, post-myocardial infarction, and in the preoperative setting. A normal stress perfusion scan predicts an extremely low rate of future cardiac events. The best predictor of future adverse cardiac events is the quantitative extent, severity, and reversibility of jeopardized myocardium, parameters that are easily assessed with perfusion scintigraphy. Although the sensitivity of scintigraphy for detecting coronary disease is high, the reported specificity of abnormal perfusion scans for predicting cardiac events is variable. Indiscriminant use of this technique with subsequent referral for angiography based on the presence of any perfusion abnormality will result in excessive, costly, and potentially dangerous screening procedures. However, thoughtful consideration of both the extent and severity of perfusion abnormality can appropriately stratify the majority of patients into low-, intermediate-, and high-risk groups. Further efforts should be directed at prospectively evaluating the use of quantitative perfusion defect and reversibility scores in various subgroups of patients to optimize the specificity of these techniques and determine the optimal degree of defect extent and severity that warrants invasive evaluation.

Coronary Disease↗
PubMed1994

Differences in indirect risk methodologies: dioxin emissions from combustion facilities.

Guidance for performing indirect risk evaluations is in a state of flux; yet, EPA and the public are insisting that estimates of indirect risks associated with combustion of industrial wastes must be derived. Two different guidance documents exist for estimating these risks: one that focuses on dioxin exposures and one that has a more general application. This paper evaluates the differences in indirect risk estimates derived from methodologies presented in these two documents and discusses those assumptions that may contribute to these differences. The influence of an individual exposure pathway on indirect risk estimates varies depending on the methodology applied. Indirect risk estimates differ by 30-fold for the same exposure pathway when comparing these methodologies. Assumptions about vapor uptake, food consumption rates, and the fraction of local food consumption appear to drive final estimates. A major discrepancy between these two documents is differences in assumptions about soil dermal contact for children. Many EPA default assumptions and values are extremely conservative and often unrealistic; therefore, use of site-specific data will be essential when estimating indirect risks associated with combustor emissions. Also, application of a toxic equivalency approach may have some benefit; risk estimates are reduced 16- to 18-fold using this approach.

Air Pollutants, Occupational↗
PubMed1994

The Australian Corneal Graft Registry (ACGR).

The value of a register of corneal grafts is that it can provide new data about the long-term outcome of corneal transplantation and may allow a more reasoned distribution of scarce donor corneas. The large numbers of cases and events can accommodate wide variations in practice patterns without losing statistical power. The Australian Corneal Graft Register follows over 6000 cases; univariate and multivariate analyses are performed every two years. Amongst the interesting recent findings of the analyses are that a past history of elevated intraocular pressure and early graft suture removal are associated with graft failure, as are the more well-established factors of inflammation, neovascularization, formation of synechiae and recurrence of herpetic eye disease. Donor corneas harvested from relatively elderly donors, however, do not appear to be associated with graft failure. Best-corrected visual acuity achieved post-operatively is very variable, but depends to some extent on the original indication for graft.

Adult↗
PubMed1994

The Northwick Park Neck Pain Questionnaire, devised to measure neck pain and disability.

Neck pain is common in rheumatological practice. Assessment of outcome is difficult without objective measures. A neck pain questionnaire using nine five-part sections has been devised to overcome this problem. Forty-four rheumatology out-patients with neck pain were studied. Questionnaires were completed on days 0 and 3-5, and at 1 and 3 months. There was good short-term repeatability (r = 0.84, kappa = 0.62). Mean scores of each of the nine sections tended to rise with that of the pain section showing internal consistency. Questions on duration and intensity of pain were good indicators of a patient's global assessment. The questionnaire is easy for patients to complete, simple to score and provides an objective measure to evaluate outcome in patients with acute or chronic neck pain.

Adult↗
PubMed1993

Asymptomatic and electrically silent myocardial ischemia during upright leg cycle ergometry and treadmill exercise (clandestine myocardial ischemia).

The frequency of "clandestine" (electrically silent and asymptomatic, but scintigraphically evident) myocardial ischemia during treadmill and upright leg cycle ergometric studies was compared in 38 patients with coronary artery disease and reversible ischemia on both thallium-201 scintigraphy and exercise radionuclide angiography. A similar peak double product was attained in both studies. Angina pectoris was significantly more frequent with treadmill exercise than with leg cycling (29 vs 5%, p = 0.0079). An interpretable and positive exercise electrocardiogram occurred in 53% of treadmill tests, but in only 19% of leg cycle tests (p = 0.0025); in a group of 22 patients without scintigraphic ischemia, leg cycle testing had greater specificity (95 vs 64%, p = 0.0248). Ischemia was manifest by symptoms or an abnormal electrocardiogram in 59% of treadmill tests, but in only 18% of leg cycle tests (p = 0.0003). There were no differences between the exercise variables or the degree of scintigraphic abnormalities of the 22 patients with manifest ischemia and the 16 with clandestine ischemia. However, patients with previous coronary artery bypass surgery experienced clandestine ischemia more frequently than did those without bypass surgery (80 vs 33%, p = 0.0103). Thus, clandestine ischemia occurs more frequently during symptom-limited upright leg cycle ergometry (82%) than during treadmill exercise (42%). The symptomatic and electrical manifestations of exercise-induced ischemia have a critical dependence on the type of exercise used.

Adult↗
PubMed1993

Mutagenesis of bacteriophage IKe major coat protein transmembrane domain: role of an interfacial proline residue.

The transmembrane (TM) domain of the 53-residue major coat protein of the M13-related bacteriophage IKe (residues 24-42: LISQTWPVVTTVVVAGVLI) has been subjected to randomized mutagenesis to probe the conformation and stability of the TM domain, as well as the effect of structurally-important residues such as proline. TM mutants were obtained by the Eckstein method of site-directed mutagenesis using the IKe genome as template so as to eliminate the need for subcloning. Over 40 single- and double-site viable mutants of bacteriophage IKe were isolated. Every residue in the TM segment, except the highly conserved Trp29, could be mutated to at least one other residue; polar and charged mutations occurred in the TM segment adjacent to the N-terminal domain (residues 24-28), while non-polar substitutions predominated in the C-terminal portion (residues 30-42). The Pro30 locus tolerated four mutations-Ala, Gly, Cys, and Ser- which represent the four side chains of least volume. Mutant coat proteins obtained directly from the phage in milligram quantities were studied by circular dichroism spectroscopy and SDS-PAGE gels. Wild type IKe coat protein solubilized in sodium deoxycholate micelles was found to occur as an alpha-helical, monomeric species which is stable at 95 degrees C, whereas the mutant Pro30-->Gly undergoes an irreversible conformational transition at ca. 90 degrees C to an aggregated beta-sheet structure. The result that Pro30 stabilizes the TM helix in the micellar membrane suggests a sterically-restricted location for the wild type Pro pyrrolidine side chain in the bulky Trp-Pro-Val triad, where it may be positioned to direct the initiation of the subsequent TM core domain helix.

Amino Acid Sequence↗
PubMed1993

Melanotropins as growth factors.

Peptides that regulate the growth of tissues, whether in a positive or negative manner, are termed growth factors. The melanocortins, neurotrophic sequences that correspond to peptide fragments contained within ACTH-(1-13), beneficially affect neural growth during development and regeneration. Analogues of ACTH-(4-9) (Org 2766) and ACTH-(4-10) (BIM 22015) are capable of sustaining neurite outgrowth from cultured dorsal root ganglion and spinal cord cells in the absence of nerve growth factor. The development of sexually dimorphic behavior in both male and female rats is influenced by perinatal administration of ACTH. This change appears to be correlated with changes in the growth and metabolism of developing serotonergic and dopaminergic systems in the hypothalamic nuclei associated with male and female sexual behavior. Similar melanotropic influences are found in the developing neuromuscular system. Neuromuscular development is accelerated by perinatal administration of melanocortins, provoking both nerve and muscle to attain early maturation. However, the responding tissue varies pivotally with age: early in gestation, embryonic muscle is acutely sensitive to peptide exposure; but once innervation has occurred, only the developing nerve reacts to melanocortin treatment. Melanocortins have little if any effect on the normal, adult neuromuscular system. Following peripheral nerve injury or pathology, melanotropins once again become effective growth factors, accelerating and enhancing nerve regeneration and muscle reinnervation. Electrophysiological, morphological, biochemical, and functional tests all indicate that ACTH-(4-10), Org 2766, BIM 22015, and alpha-MSH improve various facets of nerve regeneration, the degree to which the specific parameter is improved being dependent on the peptide fragment, its dosage, and pattern of administration. BIM 22015, while less effective as a neurotrophic factor, has potent myotrophic effects that the other peptides lack. Org 2766 may provide some protective action to the injured CNS as demonstrated by tests of cognitive function following brain lesions, although evaluation of recovery is sometimes enigmatic. Recovery from destruction of the nigrostriatal system is more easily measured through tests of motor function and open field behavior, both of which support a protective role for Org 2766. Compensatory mechanisms, including the presence of increased tyrosine hydroxylase and greater density of dopaminergic fibers, may be involved. Melanocortins are effective growth factors in sciatic nerve regeneration in neonatal rats. Both alpha-MSH and ACTH-(4-10) favor the formation of morphologically normal end plates despite the trauma following nerve crush at postnatal day 2.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenocorticotropic Hormone↗
PubMed1993

Non-random distribution of amino acids in the transmembrane segments of human type I single span membrane proteins.

The distribution of amino acids in the transmembrane segments and flanking regions of 115 human type I single span (amino terminus extracellular and carboxyl terminus cytosolic) plasma membrane proteins was found to be non-random. In this sample, Ile was preferentially localized to the amino-terminal region of the hydrophobic transmembrane segments, followed by Val, while Leu predominated in the carboxyl-terminal half of the segment. Although Gly residues were preferentially located in the transmembrane segment, this residue was excluded from the carboxyl-terminal and adjacent boundary regions. Aromatic residues (Tyr, Trp and Phe) occurred preferentially at the cytoplasmic boundary, with Trp also favored at the extracellular boundary. The extracellular flanking sequence amino-terminal to the transmembrane segment was enriched in residues predicted to initiate helix formation (Pro, Asn and Ser), while Arg and Lys were enriched in the cytoplasmic flank where they may function as topological determinants. The positional preferences of these particular amino acids within the transmembrane segment and flanking regions suggests that, in addition to lipid-protein interactions, these residues may participate in specific protein-protein interactions. A consensus sequence motif for type I membrane proteins is proposed and its role in the biosynthesis, folding, assembly and function of these segments is discussed.

Amino Acid Sequence↗
PubMed1993

True costs of air medical vs. ground ambulance systems.

The economic model created in this paper replaces the existing University of Massachusetts Medical Center's New England Life Flight (NELF) helicopter ambulance service with a ground ambulance system to investigate comparative costs. The model is based on a less than 30-minute response time to the patient, similar medical team staffing and equal service area. The annual budgetary cost of the replacement ground network is $3,804,000 while the helicopter ambulance costs are $1,686,500 (based on 1991 dollars). The cost per patient transported is $4,475 for the ground system and $2,811 for the helicopter system. The comparison finds that the commonly held notion that condemns helicopters as an excessively expensive technology for patient transport is incorrect. Future research to address intermediate alternatives using similar analytical technology assessment techniques is recommended.

Aircraft↗
PubMed1993

Storage, surgery, outcome, and complications of corneal and conjunctival grafts.

Corneal transplantation is still limited by a shortage of donor material, but the type of storage medium used once a cornea has been acquired is probably irrelevant to graft outcome. Vancomycin HCl shows promise as a supplement to gentamicin sulfate in storage media. New methods of HLA typing using donor ocular tissue have largely helped to overcome the problems associated with typing of cadaveric blood, but the value of HLA typing in improving corneal graft survival is now in doubt. Alternative regimens of immunosuppression are being tested in animal models, but there is still no consensus on the best ways to use existing agents such as corticosteroids. Rejection remains the most common cause of unsuccessful corneal grafting in large cohorts, but glaucoma and astigmatism also limit postoperative graft function. Limbal stem cell grafts are promising for the management of many ocular surface diseases and conjunctival limbal autografts for pterygia may be the most successful surgical method for preventing recurrence.

Anti-Bacterial Agents↗
PubMed1993

The structure and function of central nervous system myelin.

Multiple sclerosis (MS) is characterized by the active degradation of central nervous system myelin, a multilamellar membrane system that insulates nerve axons. MS arises from complex interactions between genetic, immunological, infective, and biochemical mechanisms. Although the circumstances of MS etiology remain hypothetical, one persistent theme involves immune system recognition of myelin-specific antigens derived from myelin basic protein, the most abundant extrinsic myelin membrane protein, and/or another equally suitable myelin protein or lipid. Knowledge of the biochemical and physical-chemical properties of myelin proteins, and lipids, particularly their composition, organization, structure, and accessibility with respect to the compacted myelin multilayers, thus becomes central to understanding how and why these antigens become selected during the development of MS. This article focuses on the current understanding of the molecular basis of MS as it may relate to the protein and lipid components of myelin, which dictate myelin morphology on the basis of protein-lipid and lipid-lipid interactions, and the relationship, if any, between the protein/lipid components and the destruction of myelin in pathological situations.

Amino Acid Sequence↗
PubMed1993

First-pass radionuclide angiographic studies of left ventricular function with technetium-99m-teboroxime, technetium-99m-sestamibi and technetium-99m-DTPA.

Technetium-99m-teboroxime (BATO) and 99mTc-sestamibi (MIBI) may provide the opportunity for first-pass evaluation of left and right ventricular function at rest and exercise in conjunction with myocardial perfusion scintigraphy. This study examined the results of age- and gender-matched patients with clinically normal left ventricular function who underwent resting first-pass studies with BATO (n = 25), MIBI (n = 25) and DTPA (n = 25). There were no significant differences between the observed first-pass tracer kinetics or clinical results of MIBI and DTPA. However, there was significantly greater first-pass pulmonary uptake of BATO compared with either MIBI or DTPA. This resulted in five clinically important differences in the BATO FPRNA images: (1) greater background during the levophase of the tracer transit, (2) prolongation of the measured mean pulmonary transit time, (3) lower raw and final ejection fractions, (4) obscured left ventricular border definition resulting in larger geometrically derived left ventricular volumes and (5) poorer image detail and quality which compromised functional image and regional wall motion interpretation. This study suggests that further refinement of the first-pass methodology, particularly with regard to methods of background subtraction, is needed to obtain quality FPRNA results with BATO. However, for the purposes of left ventricular function analysis with FPRNA, MIBI and DTPA are interchangeable.

Female↗
PubMed1992

Transplantation of the cornea.

Corneal transplantation is the most widely practised form of allografting in clinical practice. The operation is used to correct developmental abnormalities of corneal shape such as keratoconus, to overcome opacities of the cornea, to relieve pain and to mend perforations. Corneal transplantation is generally successful but contrary to popular belief, corneal grafts can be rejected. This is a particular problem for patients treated for the sequelae of inflammatory disease. The relative importance of measures such as systemic immunosuppression and tissue typing is less in corneal transplantation than in other forms of clinical allografting. Overcoming rejection, achieving the best optical configuration in a graft, and increasing the number of donor corneas available for transplantation represent the main avenues for achieving improvements in corneal transplantation.

Cornea↗
PubMed1992

Linguistic experience alters phonetic perception in infants by 6 months of age.

Linguistic experience affects phonetic perception. However, the critical period during which experience affects perception and the mechanism responsible for these effects are unknown. This study of 6-month-old infants from two countries, the United States and Sweden, shows that exposure to a specific language in the first half year of life alters infants' phonetic perception.

Analysis of Variance↗