Isolation of insoluble secretory product from bovine thyroid: extracellular storage of thyroglobulin in covalently cross-linked form. Extracellular storage of thyroglobulin (TG) is an important prerequisite for maintaining constant levels of thyroid hormones in vertebrates. Storage of large amounts is made possible by compactation of TG in the follicle lumen with concentrations of at least 100-400 mg/ml. We recently observed that the luminal content from bovine thyroids can be isolated in an intact state and be separated from soluble TG. For this purpose, bovine thyroid tissue was homogenized and subjected to various steps of purification. This procedure resulted in a pellet of single globules measuring 20-120 microns in diameter. Scanning electron microscopy revealed a unique cobblestone-like surface pattern of isolated globules, showing in detail the impressions of the apical plasma membranes of thyrocytes which had formerly surrounded the luminal content before tissue homogenization. Isolated thyroid globules were rapidly digested by trypsin but extremely resistant to various protein solubilization procedures. Homogenization of isolated globules resulted in the release of approximately 3% of total protein, showing that only a minor proportion of TG was loosely incorporated in thyroid globules whereas approximately 22% appeared to be interconnected with the globule matrix by disulfide bridges. Analysis by SDS-gel electrophoresis and immunoblotting confirmed that the protein released by this procedure consisted of TG. The vast majority (approximately 75%) of the globule matrix protein was found to be covalently cross-linked by non-disulfide bonds. TG in isolated globules was highly iodinated (approximately 55 iodine atoms per 12-S TG subunit) suggesting that the covalent nondisulfide cross-linking occurs in part during the iodination of TG and that this process involves the formation of intermolecular dityrosine bridges. Mechanisms must exist which solubilize or disperse the insoluble luminal content prior to endocytosis of TG.


Role of the COOH-terminal nonhelical tailpiece in the assembly of a vertebrate nonmuscle myosin rod. A short nonhelical sequence at the COOH-terminus of vertebrate nonmuscle myosin has been shown to enhance myosin filament assembly. We have analyzed the role of this sequence in chicken intestinal epithelial brush border myosin, using protein engineering/site-directed mutagenesis. Clones encoding the rod region of this myosin were isolated and sequenced. They were truncated at various restriction sites and expressed in Escherichia coli, yielding a series of mutant myosin rods with or without the COOH-terminal tailpiece and with serial deletions from their NH2-termini. Deletion of the 35 residue COOH-terminal nonhelical tailpiece was sufficient to increase the critical concentration for myosin rod assembly by 50-fold (at 150 mM NaCl, pH 7.5), whereas NH2-terminal deletions had only minor effects. The only exception was the longest NH2-terminal deletion, which reduced the rod to 119 amino acids and rendered it assembly incompetent. The COOH-terminal tailpiece could be reduced by 15 amino acids and it still efficiently promoted assembly. We also found that the tailpiece promoted assembly of both filaments and segments; assemblies which have different molecular overlaps. Rod fragments carrying the COOH-terminal tailpiece did not promote the assembly of COOH-terminally deleted material when the two were mixed together. The tailpiece sequence thus has profound effects on assembly, yet it is apparently unstructured and can be bisected without affecting its function. Taken together these observations suggest that the nonhelical tailpiece may act sterically to block an otherwise dominant but unproductive molecular interaction in the self assembly process and does not, as has been previously thought, bind to a specific target site(s) on a neighboring molecule.


Kinectin, a major kinesin-binding protein on ER. Previous studies have shown that microtubule-based organelle transport requires a membrane receptor but no kinesin-binding membrane proteins have been isolated. Chick embryo brain microsomes have kinesin bound to their surface, and after detergent solubilization, a matrix with an antibody to the kinesin head domain (SUK-4) (Ingold et al., 1988) bound the solubilized kinesin and retained an equal amount of a microsome protein of 160-kD. Similarly, velocity sedimentation of solubilized membranes showed that kinesin and the 160-kD polypeptide cosedimented at 13S. After alkaline treatment to remove kinesin from the microsomes, the same 160-kD polypeptide doublet bound to a kinesin affinity resin and not to other proteins tested. Biochemical characterization localized this protein to the cytoplasmic face of brain microsomes and indicated that it was an integral membrane protein since it was resistant to alkaline washing. mAbs raised to chick 160-kD protein demonstrated that it was absent in the supernatant and concentrated in the dense microsome fraction. The dense microsome fraction also had the greatest amount of microtubule-dependent motility. With immunofluorescence, the antibodies labeled the ER in chick embryo fibroblasts (similar to the pattern of bound kinesin staining in the same cells) (Hollenbeck, P. J. 1989. J. Cell Biol. 108:2335-2342), astroglia, Schwann cells and dorsal root ganglion cells but staining was much less in the Golgi regions of these cells. Because this protein is a major kinesin-binding protein of motile vesicles and would be expected to bind kinesin to the organelle membrane, we have chosen the name, kinectin, for this protein.


Transcripts for the acetylcholine receptor and acetylcholine esterase show distribution differences in cultured chick muscle cells. In situ hybridization of chick cultured muscle cells using exonic DNA probes for both AChR alpha-sub-unit and the catalytic subunit of AChE, revealed major differences in the distribution of label both over nuclei and in their surrounding cytoplasm, although some overlap in these distributions exists. For the AChR alpha-subunit there is a highly skewed distribution of labeled nuclei, with 35% of the nuclei being relatively inactive (less than 0.25 times the mean label) and approximately 10% being very heavily labeled (greater than 2.5 times the mean label). In contrast the nuclei labeled with the exonic probe for the AChE transcripts had a more Gaussian distribution, yet with some slight skewness in the direction of a few heavily labeled nuclei. There was also a difference in the cytoplasmic distribution of the label. The AChR alpha-subunit mRNA was mainly within 4 microns of labeled nuclei while the AChE mRNA was more widely distributed throughout the cytoplasm, possibly within a 10 microns rim around labeled nuclei. An intronic probe for the AChE gave the identical distribution of nuclear label to that of the exonic probe (but without any cytoplasmic label). In addition, calibration of the technique indicated that per myotube the AChE transcript is about sixfold more abundant than the AChR alpha-subunit transcript.


A GTPase controls cell-substrate adhesion in Xenopus XTC fibroblasts. Cell-substrate adhesion is crucial at various stages of development and for the maintenance of normal tissues. Little is known about the regulation of these adhesive interactions. To investigate the role of GTPases in the control of cell morphology and cell-substrate adhesion we have injected guanine nucleotide analogs into Xenopus XTC fibroblasts. Injection of GTP gamma S inhibited ruffling and increased spreading, suggesting an increase in adhesion. To further investigate this, we made use of GRGDSP, a peptide which inhibits binding of integrins to vitronectin and fibronectin. XTC fibroblasts injected with non-hydrolyzable analogs of GTP took much more time to round up than mock-injected cells in response to treatment with GRGDSP, while GDP beta S-injected cells rounded up in less time than controls. Injection with GTP gamma S did not inhibit cell rounding induced by trypsin however, showing that cell contractility is not significantly affected by the activation of GTPases. These data provide evidence for the existence of a GTPase which can control cell-substrate adhesion from the cytoplasm. Treatment of XTC fibroblasts with the phorbol ester 12-o-tetradecanoylphorbol-13-acetate reduced cell spreading and accelerated cell rounding in response to GRGDSP, which is essentially opposite to the effect exerted by non-hydrolyzable GTP analogs. These results suggest the existence of at least two distinct pathways controlling cell-substrate adhesion in XTC fibroblasts, one depending on a GTPase and another one involving protein kinase C.


Nectadrin, the heat-stable antigen, is a cell adhesion molecule. Nectadrin, the cell surface glycoprotein recognized by the novel mAb 79, was found to be immunologically identical to the heat-stable antigen (HSA). It is a glycoprotein with a polypeptide core of only 30 amino acids and a very high carbohydrate content (Wenger, R. H., M. Ayane, R. Bose, G. Köhler, and P. J. Nielsen. 1991. Eur. J. Immunol. 21:1039-1046). Immunocytological studies using cultured splenic B-lymphocytes, neuroblastoma cells, and cerebellar cells indicated that nectadrin is preferentially expressed at sites of cell-cell contact. Purified nectadrin and monoclonal nectadrin antibody 79, but not other monoclonal nectadrin antibodies, inhibited the aggregation of B-lymphocytes by 70%, suggesting that nectadrin may act as a cell adhesion molecule. Nectadrin was purified from a mouse lymphoma cell line in two forms of 40-60 and 23-30 kD. The lower molecular weight form appears to be generated from the higher molecular weight form by degradative removal of saccharide residues characteristic of complex type oligosaccharide side chains. Latex beads coated with purified nectadrin aggregated and the rate of their aggregation depended on the molecular form of nectadrin, with the larger form being more potent than the smaller one in mediating bead aggregation. Nectadrin thus appears to be a self-binding cell adhesion molecule of a structurally novel type in that its extensive glycan structures may be implicated in mediating cell adhesion.


Bravo/Nr-CAM is closely related to the cell adhesion molecules L1 and Ng-CAM and has a similar heterodimer structure. Diverse cell-surface molecules of the nervous system play an important role in specifying cell interactions during development. Using a method designed to generate mAbs against neural surface molecules of defined molecular weight, we have previously reported on the surface protein, Bravo, found in the developing avian retinotectal system. Bravo is immunologically detected on developing optic fibers in the retina, but absent from distal regions of the same fibers in the tectum. We have isolated cDNA clones encompassing the entire coding region of Bravo, including clones containing five alternative sequences of cDNA. These putative alternatively spliced sequences encode stretches of polypeptide ranging in length from 10-93 amino acids and are predicted to be both extra- and intracellular. The deduced primary structure of Bravo reveals that, like the cell adhesion molecules (CAMs) chicken Ng-CAM and mouse L1, Bravo is composed of six Ig-like domains, five fibronectin type III repeats, a transmembrane domain, and a short cytoplasmic region. Recently, the cDNA sequence of a related molecule, Nr-CAM, was reported and its possible identity with Bravo discussed (Grumet, M., V. Mauro, M. P. Burgoon, G. E. Edelman, and B. A. Cunningham. 1991. J. Cell Biol. 113:1399-1412). Here we confirm this identity and moreover show that Bravo is found on Müller glial processes and end-feet in the developing retina. In contrast to the single polypeptide chain structure of Nr-CAM reported previously, we show that Bravo has a heterodimer structure composed of an alpha chain of M(r) 140/130 and a beta chain of 60-80 kD. As with L1 and Ng-CAM, the two chains of Bravo are generated from an intact polypeptide by cleavage at identical locations and conserved sites within all three molecules (Ser-Arg/Lys-Arg). The similar domain composition and heterodimer structure, as well as the 40% amino acid sequence identity of these molecules, defines them as an evolutionarily related subgroup of CAMs. The relationship of Bravo to molecules known to be involved in cell adhesion and process outgrowth, combined with its pattern of expression and numerous potential isoforms, suggests a complex role for this molecule in cell interactions during neural development.


Coordinated expression of extracellular matrix-degrading proteinases and their inhibitors regulates mammary epithelial function during involution. Extracellular matrix (ECM) plays an important role in the maintenance of mammary epithelial differentiation in culture. We asked whether changes in mouse mammary specific function in vivo correlate with changes in the ECM. We showed, using expression of beta-casein as a marker, that the temporal expression of ECM-degrading proteinases and their inhibitors during lactation and involution are inversely related to functional differentiation. After a lactation period of 9 d, mammary epithelial cells maintained beta-casein expression up to 5 d of involution. Two metalloproteinases, 72-kD gelatinase (and its 62-kD active form), and stromelysin, and a serine proteinase tissue plasminogen activator were detected by day four of involution, and maintained expression until at least day 10. The expression of their inhibitors, the tissue inhibitor of metalloproteinases (TIMP) and plasminogen activator inhibitor-1, preceded the onset of ECM-degrading proteinase expression and was detected by day two of involution, and showed a sharp peak of expression centered on days 4-6 of involution. When involution was accelerated by decreasing lactation to 2 d, there was an accelerated loss of beta-casein expression evident by day four and a shift in expression of ECM-remodeling proteinases and inhibitors to a focus at 2-4 d of involution. To further extend the correlation between mammary-specific function and ECM remodeling we initiated involution by sealing just one gland in an otherwise hormonally sufficient lactating animal. Alveoli in the sealed gland contained casein for at least 7 d after sealing, and closely resembled those in a lactating gland. The relative expression of TIMP in the sealed gland increased, whereas the expression of stromelysin was much lower than that of a hormone-depleted involuting gland, indicating that the higher the ratio of TIMP to ECM-degrading proteinases the slower the process of involution. To test directly the functional role of ECM-degrading proteinases in the loss of tissue-specific function we artificially perturbed the ECM-degrading proteinase-inhibitor ratio in a normally involuting gland by maintaining high concentrations of TIMP protein with the use of surgically implanted slow-release pellets. In a concentration-dependent fashion, involuting mammary glands that received TIMP implants maintained high levels of casein and delayed alveolar regression. These data suggest that the balance of ECM-degrading proteinases and their inhibitors regulates the organization of the basement membrane and the tissue-specific function of the mammary gland.(ABSTRACT TRUNCATED AT 400 WORDS)


Conjunctival epithelial cells from patients with Sjögren's syndrome inappropriately express major histocompatibility complex molecules, La(SSB) antigen, and heat-shock proteins. The La(SSB) antigen has been detected within the cytoplasm and on the membrane of conjunctival cells (CC) from patients with Sjögren's syndrome, whereas it was weakly expressed in the nucleus of normal cells. The diseased CC were shown to overproduce major histocompatibility complex (MHC) class I antigens and express MHC class II antigens. Anti-heat-shock protein monoclonal antibody bound to the cell membrane in patients but not in normal controls.


Chronic enteroviral meningoencephalitis in agammaglobulinemia: case report and literature review. Chronic enteroviral meningoencephalitis is a well-recognized complication in patients with X-linked agammaglobulinemia (XLA). The majority of published cases refers to its occurrence in patients on no replacement therapy or on only intramuscular immunoglobulin. The advent of intravenous immunoglobulin (IVIg) in the early 1980s and its widespread use in XLA was thought to have virtually eradicated enteroviral meningoencephalitis in these patients. We describe the development of echovirus meningoencephalitis in an 11-year-old boy on regular IVIg replacement whose serum IgG levels were maintained at between 6 and 8 g/L (NR 6-13 g/L). Treatment with daily high-dose IVIg was commenced, with significant clinical improvement being noted within a few weeks in association with a reduction in blood-brain barrier permeability. The persistence of live virus, however, necessitated the use of intraventricular immunoglobulin. The virus proved resistant to two courses of specific intraventricular immunoglobulin and a 6-week course of oral ribavirin and eventually proved fatal 5 months after presentation. In view of the therapeutic uncertainties we have reviewed the use of immunoglobulin in the treatment of enteroviral meningoencephalitis over the past 6 years.


Major histocompatibility complex (MHC) class II restriction, lymphokine production, and IgE regulation of house dust mite-specific T-cell clones. To elucidate the regulatory mechanism of human IgE synthesis, we have cloned house dust mite (Dermatophagoides pteronyssinus; Dp)-specific T-cell clones from three asthmatic children and three healthy individuals. Twelve clones were cloned from each group. All of these clones were CD3+, CD4+, CD8-, and HLA-DR+. After stimulation with allergen in the presence of antigen presenting cells (APCs), half of the T-cell clones from asthmatic children and one-third of those from normals produced interleukin 4 (IL-4). None of the patients' clones produced interferon gamma (IFN-gamma), while 10 of 12 normals' clones did. After stimulation with calcium ionophore A23187 and phorbol myristic acetate (PMA), the production of IL-4 was markedly increased in both patients and normals. However, only 3 of the 12 patients' clones produced IFN-gamma, while all of the normals' clones did. The T-cell clones of both patients and normals produced comparable IL-2. To study the kinetics of lymphokine productions, a HLA-DRw12-restricted T-cell clone (FYD 3.1) was stimulated, respectively, with a combination of A23187 and PMA, phytohemagglutinin (PHA), or Dp antigen in the presence of APCs. Maximal IL-2 and IL-4 productions were detected 12 hr after A23187 and PMA stimulation, whereas IFN-gamma could not be detected even 36 hr after stimulation. When stimulated with PHA, the production of IFN-gamma peaked on the fourth day, but IL-4 was not detected. After stimulation with Dp antigen and APCs, IL-4 and IL-2 were detected on the second and third days, but IFN-gamma was not detected. The IgE production by autologous purified B cells in the presence of allergen or IL-4 was found to be augmented by the FYD 3.1 T-cell clones. IFN-gamma was observed to counteract the effects of the T-cell clones and IL-4. Thus, the secretory patterns of lymphokine and kinetics of lymphokine production of allergen-specific T-cell clones can be used to explore the regulatory mechanism of human IgE synthesis [corrected].


Induction of lymphokine-activated killer cells with low-dose interleukin 2 and interferon-gamma in oral cancer patients. Lymphokine-activated killer (LAK) cells were induced with low-dose recombinant interleukin 2 (rIL-2) and recombinant interferon-gamma (IFN-gamma) in 28 oral carcinoma patients. The patients received daily intravenous injections of rIL-2 (1.2 x 10(5) U/m2) and rIFN-gamma (7.0 x 10(4) U/m2), and both natural killer (NK) and LAK activities were periodically examined. A significant increase in CD16+CD57+ and CD16+CD57- NK subsets was observed after the induction. An increase in the T-cell population was also found, with a significant increase in CD3+HLA-DR+, CD8+Leu8-, and CD4+Leu8- cells. Significant increases in NK activity, from the original level of 32.0 +/- 13.7 to 49.9 +/- 15.2%, and LAK activity, from 4.8 +/- 3.5 to 11.0 +/- 6.1%, at Day 7 were observed. Both activities were maintained at high levels during the cytokine injections, but greater enhancement of the killing activities could not be obtained subsequently. When NK and LAK activities were investigated in each subpopulation of CD3- and CD16- cells, no remarkable cytotoxic activity could be observed before induction in any subset without NK activity in CD3- cells (31.1 +/- 14.3%). At Day 7, NK activity of CD16- cells increased up to 21.4 +/- 14.9%, accompanied by an increase in CD3(-)-cell activity (54.5 +/- 20.6%). LAK activities of both subsets were also enhanced, with activity at Day 7 of 6.5 +/- 5.6 and 9.4 +/- 6.6% in CD16- and CD3- cells, respectively. These increased activities were maintained at the same level during the induction. Phorbol myristate acetate-induced polymorphonuclear leukocyte (PMNL) O2-generation was significantly increased, from the original 81.1 +/- 28.1 to 95.6 +/- 34.9 pmol/min/10(4) cells, after 1 week of treatment. Protein kinase C activity in the cytosol decreased, and the activity in the membrane fraction conversely increased. No remarkable adverse effects except for mild fever were observed. Together with LAK induction ability and PMNL enhancement, with scarce toxicity, a combination of low-dose rIL-2 and rIFN-gamma is thought to be useful in cancer treatments.


Altered cytokine production in black patients with keloids. The treatment of keloids in black patients remains a medical dilemma. Previous studies have focused on primary alterations in the metabolism of fibroblasts as the key in the etiology of this condition. Yet alterations in the production of various cytokines which may alter fibroblast responses secondarily have received little attention. Twelve black patients with clinical and histological diagnosis of keloids and eight black control volunteers were studied. Peripheral blood mononuclear-cell (PBMC) fractions from both groups were assayed for production of interleukin-1 (IL-1), interleukin-2 (IL-2), interleukin-6 (IL-6), alpha-interferon (IFN-alpha), beta-interferon (IFN-beta), gamma-interferon (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and tumor necrosis factor-beta (TNF-beta). The production of IFN-alpha, IFN-gamma, and TNF-beta were markedly depressed in keloid patients compared to normal controls. However, IL-1 and IL-2 production was not significantly different between the two groups. In contradistinction, keloid patients produce greater amounts of IL-6, TNF-alpha, and IFN-beta. Altered levels of immunoregulatory cytokines may play a significant role in the net increase in collagen which characterizes keloid formation.


Why do elderly people seek professional home care? Methodologies compared. In order to investigate which characteristics, besides physical limitations, of elderly people living at home contribute to the utilization of professional home care, a study was conducted in which 450 elderly people aged 55 and over, 123 with and 327 without professional home care, were interviewed. To obtain a selection for the interviews, a postal questionnaire, containing questions on functional status and care utilization, sent out to a random sample of the elderly people (55+) living at home (n = 2451), preceded the actual interviews. The oral interviews yielded the same information, plus an inventory of aspects of the mental status, the social network, the socio-economic status and the housing condition. Analysis was performed in three ways: bivariate analysis, logistic regression analysis and discriminant analysis. The bivariate analysis revealed that users of professional care were older, more often female and more often not married. Their social network was less extensive, as they received less informal care and lived alone more often. Besides they had more mental and financial problems. From the regression analysis it appeared that, in addition to the functional status, the amount of informal care and the household composition contributed to the utilization of professional home care. For the other characteristics inventoried, no independent association with the utilization of professional care could be established. With hindsight, it appeared that in this study long interviews hardly had additional value over postal questionnaires, in which the contribution of functional status and informal care to professional care was already discovered.


Recognition of depression by internal medicine residents. We studied the ability of internal medicine residents to recognize depressive symptoms in a population of lower socio-economic primary care patients. Four hundred twenty patients completed the short form of the Beck Depression Inventory (BDI). Simultaneously, the resident caring for the patient estimated the degree of depression for each patient. One-fourth of the patients scored at or above the moderately depressed level on the BDI and the residents rated 23 percent of their patients as at least moderately depressed. However, the accuracy of the residents' assessment of his or her individual patient was poor (correlation = 0.42, sensitivity = 0.46, specificity = 0.84). Patients with a prior history of psychiatric disorder scored higher on the BDI and were given higher ratings of depression. No other pre-existing medical condition was significantly associated with a higher or lower BDI score. The amount of alcohol consumed and the amount smoked, were both associated with higher BDI scores. Residents varied in their sensitivity to their patients' BDI scores. Some showed high agreement with BDI scores, others low. There were no specific resident characteristics (e.g. year of training, resident gender) that could explain this variability. Patients with a history of depression were given lower resident ratings compared to other patients and patients with a history of depression were given lower resident ratings than predicted by their BDI scores. Residents' ability to accurately diagnose and treat depression in the underprivileged primary care patient can be facilitated by the institution of depression screening in the ambulatory clinic.


How sources of health information relate to knowledge and use of cancer screening exams. Utilization of many screening procedures to detect cancer in early stages remains low. In order to design more effective strategies to increase utilization of these tests, we assessed the role and relative importance of different information sources on knowledge and use of cancer screening exams. Where individuals get useful information about disease prevention, and the relationship of information sources to cancer screening knowledge and behavior are reported using data from the 1987 National Health Interview Survey. Results indicate that physicians are perceived as important sources of information on how to prevent illness. However, persons who use print media as their most useful source of information are significantly more likely to have heard of cancer screening procedures than those who rely on the doctor as the source. Those who rely on electronic media tend to be less knowledgeable of all screening procedures examined. A strong and consistent association between doctor as the most useful source of information and actually having received the procedure was found. These results suggest that knowledge may not necessarily be a prerequisite to screening and indicate that reliance on the physician to recommend cancer screening may be critical in utilization of these services.


Improving future preventive care through educational efforts at a women's community screening program. Cervical cancer mortality continues to be a significant problem in the United States. Pap Test screening programs have been effective in attracting high risk women, but the impact of these programs on subsequent health care has seldom been explored. This follow up study examined the impact of a cervical cancer screening and education program on preventive health behaviors of New Hampshire women in the 24 months following the screening program. A mailed survey was sent to a random sample of 750 women from program participants to evaluate both their recent preventive health care practices and to identify perceived barriers to obtaining preventive health services. Of these, 71.1 percent responded. Survey responses of the original program participants were linked to each subject's previous answers to the same questions asked 24 months earlier. A comparison group was derived by asking follow up study participants to identify a female acquaintance within five years of her age. Seventy-four percent of the comparison group responded. Survey responses of original program participants were then compared to those of the comparison group. Results indicate that women who participated in the original Project received significantly more preventive health care services in the two years since the Project than in the two years prior to it. Women in the comparison group received more Paps and clinical breast examinations than women in the participant group, perhaps because all participants had received a Pap test two years before. Having a regular health care provider was the most significant characteristic associated with obtaining indicated preventive services. An important contribution of community screening programs may be to encourage women to establish a regular source of care.


Dental prosthetic status and needs of an elderly population living in long-term care facilities in Singapore. This study examined the prosthetic status and needs among an elderly population living in long-term care facilities in Singapore. A total of 488 subjects were randomly selected and 479 of them were examined. The results show that 56.2 percent of selected subjects were edentulous while 43.8 percent had one or more teeth missing. The average number of teeth present among dentate subjects was 7.5. Of the edentulous subjects, 78 percent of them reported not having any dentures, and more than 20 percent of existing dentures were found to be defective and had to be replaced. A higher proportion (94 percent) of dentate subjects who could have benefitted from having partial dentures did not have them. The findings of this study clearly demonstrate high unmet needs for prosthetic care among an institutionalized elderly population.


Soft tissue augmentation of periorbital fine lines and the orbital groove with Zyderm-I and fine-gauge needles. A new procedure utilizing Zyderm-I (Collagen Biomedical, Palo Alto, CA) and a 32-gauge needle for augmentation of the periorbital fine lines and the orbital groove is described. This advanced soft tissue augmentation technique is described in detail in 30 patients with before, after, and 1-week post-augmentation photographs presented by the author. This technique requires familiarity with soft tissue augmentation and the use of collagen injectable materials as well as specific training on a one-to-one basis with someone experienced with this particular technique.


A review of sutures and suturing techniques. The ideal suture is strong, handles easily, and forms secure knots. It causes minimal tissue inflammation and does not promote infection. It stretches and accommodates wound edema. Although no single suture possesses all of these features, proper selection of sutures helps achieve better results in skin surgery. Proper suturing technique is essential for obtaining good cosmetic results and avoiding scarring and poor wound healing. Techniques that must be mastered include good eversion of skin edges, avoiding suture marks, maintaining uniform tensile strength along the skin edges, and precise approximation along skin edges.


Extensive scalp lifting. Decrease in complications utilizing unilateral occipital artery ligation and other modifications. The superior yield from extensive scalp lifting has been detracted from by complications, including hemorrhage, scalp necrosis, and the need for greater anesthesia. Intraoperative unilateral occipital artery ligation, with extensive undermining to the nape of the neck on only one side, can minimize the risk of postoperative scalp necrosis or telogen effluvium. Careful hemostasis, extensive infusion of dilute anesthetic, and modifications in instrumentation can decrease the morbidity associated with this procedure. The advantages of the operation include removal of the large amounts of bald scalp, excellent intraoperative visualization, and lack of stretchback and asymmetry.


Extensive scalp lifting as a reconstructive tool for a large scalp defect. Extensive scalp lifting is a relatively new technique for the treatment of alopecia. Because this technique involves the undermining of the entire occipitoparietal scalp down to the hairline of the nape, a significant anterior and medial advancement is accomplished with one operation. This case report describes a patient with a large surgically induced scalp defect that was reconstructed with the use of extensive scalp lifting in combination with coronal brow lifting--thus, the intermediate cosmetic deformity of the more commonly used tissue expansion technique was completely circumvented. Why this technique can be substituted for tissue expansion or multiple rotation-transposition flaps in certain cases in elaborated.


The purse-string suture in facial reconstruction. Mohs surgical defects in 26 patients were reconstructed utilizing a purse-string suture and a full-thickness graft. The placement of the purse-string suture decreased the surface area of the wound an average of 53%. A full-thickness graft was then placed in the remaining defect. This technique enabled us to repair large wounds of the facial region with a relatively small full-thickness graft. There were no complications in our series. The resultant areas were cosmetically acceptable and resistant to trauma.


Q-switched ruby laser treatment of nevus of Ota. Emission of 694-nm laser energy from a Q-switched ruby laser causes photodestruction of cutaneous pigment. The 40-nanosecond pulse duration of Q-switched ruby laser light initiates specific damage to melanosomes thus allowing selective treatment of benign pigmented lesions. Nevus of Ota is a benign facial oculocutaneous melanosis that has melanosomes lying deeply within the dermis. We report the successful use of the Q-switched ruby laser in the treatment of two patients with the nevus of Ota.


Tissue sparing repair. A new approach to shorten excisional lines. Tissue sparing repair uses primary closure to make a circular or irregular defect into a line. The resultant closure ratio is 1.5:1 without a dog-ear defect for circular closures. Irregular defects will have different closure ratios. Two new suture techniques are used: 1) the horizontal oblique dermal suture, which approximates tissue without undermining and with minimal epidermal wound edge tension; and 2) the apex cutaneous suture, which repairs most dog-ear defects with a suture. Tissue sparing repair may be a useful addition to primary wound closure.


An objective quality assessment method for bit-reduction coding of wideband speech. This paper proposes a new objective quality assessment method for bit-reduction coding of wideband speech taking into account the masking effect of quantizing noise. First, this paper analyzes the reliability and sensitivity of the speech quality assessment method, based on a paired-comparison test with a modulated noise reference signal, for the bit-reduction coding of high-quality wideband speech. Then, the perception of quantizing noise is studied using speech with noise synthesized similar to the quantizing noise. The detection of quantizing noise is found to be influenced by masking by the source signal. This leads to a new method of objectively estimating the quality of coding speech by multiple regression analysis. The factors for the estimation are segmental signal-to-noise ratio, spectrum envelope distance between source signal and quantizing noise, and the similarity of the noise power envelope to the source signal in the time domain. This estimation method is applied to the parameter optimization of wideband coding systems.


Formant movements of Dutch vowels in a text, read at normal and fast rate. Speaking rate in general, and vowel duration more specifically, is thought to affect the dynamic structure of vowel formant tracks. To test this, a single, professional speaker read a long text at two different speaking rates, fast and normal. The present project investigated the extent to which the first and second formant tracks of eight Dutch vowels varied under the two different speaking rate conditions. A total of 549 pairs of vowel realizations from various contexts were selected for analysis. The formant track shape was assessed on a point-by-point basis, using 16 samples at the same relative positions in the vowels. Differences in speech rate only resulted in a uniform change in F1 frequency. Within each speaking rate, there was only evidence of a weak leveling off of the F1 tracks of the open vowels /a a/ with shorter durations. When considering sentence stress or vowel realizations from a more uniform, alveolar-vowel-alveolar context, these same conclusions were reached. These results indicate a much more active adaptation to speaking rate than implied by the target undershoot model.


Production of the word-final English /t/-/d/ contrast by native speakers of English, Mandarin, and Spanish. The primary aim of this study was to determine if adults whose native language permits neither voiced nor voiceless stops to occur in word-final position can master the English word-final /t/-/d/ contrast. Native English-speaking listeners identified the voicing feature in word-final stops produced by talkers in five groups: native speakers of English, experienced and inexperienced native Spanish speakers of English, and experienced and inexperienced native Mandarin speakers of English. Contrary to hypothesis, the experienced second language (L2) learners' stops were not identified significantly better than stops produced by the inexperienced L2 learners; and their stops were correctly identified significantly less often than stops produced by the native English speakers. Acoustic analyses revealed that the native English speakers made vowels significantly longer before /d/ than /t/, produced /t/-final words with a higher F1 offset frequency than /d/-final words, produced more closure voicing in /d/ than /t/, and sustained closure longer for /t/ than /d/. The L2 learners produced the same kinds of acoustic differences between /t/ and /d/, but theirs were usually of significantly smaller magnitude. Taken together, the results suggest that only a few of the 40 L2 learners examined in the present study had mastered the English word-final /t/-/d/ contrast. Several possible explanations for this negative finding are presented. Multiple regression analyses revealed that the native English listeners made perceptual use of the small, albeit significant, vowel duration differences produced in minimal pairs by the nonnative speakers. A significantly stronger correlation existed between vowel duration differences and the listeners' identifications of final stops in minimal pairs when the perceptual judgments were obtained in an "edited" condition (where post-vocalic cues were removed) than in a "full cue" condition. This suggested that listeners may modify their identification of stops based on the availability of acoustic cues.


Temporal decline of masking and comodulation masking release. Masking sounds can be continuously present, gated simultaneously with the signal, or gated somewhat prior to the signal. This continuum of relative onset times was explored using waveforms of the sort commonly employed in studies of comodulation masking release (CMR). There was a 50-Hz masker band centered on the 1250-Hz tonal signal, and four 50-Hz flanker bands centered at 850, 1050, 1450, and 1650 Hz. In some conditions, all four flanker bands had the same temporal envelope, and the masker band either had that same envelope (correlated presentations) or a different envelope (uncorrelated presentations). In other conditions, all five bands had different temporal envelopes (all-uncorrelated presentations). The masker band and/or the four flanker bands were either gated nearly simultaneously with the signal (burst conditions) or were gated prior to the signal by a duration that was systematically varied (fringed conditions). The eight listeners could be partitioned into three groups on the basis of their response to these fringing manipulations. Two listeners (the large fringers) showed a gradual improvement in detectability with increasing fringe duration (called a temporal decline of masking), while three others (the small fringers) showed little improvement in detectability. For the remaining three subjects, there was evidence of a "learning" effect that changed them from large fringers to small fringers over a 10-week period of listening. When present, the temporal decline of masking was greater for the correlated than for the uncorrelated comodulation condition; as a consequence, the difference in detectability between them (the comodulation masking release or CMR) increased with fringe duration. By fringing the masker and flanker bands separately and in combination, it was revealed that the temporal declines of masking were primarily attributable to the fringing of the flanker bands. In contrast, large CMRs required long fringes on both the masker and flanker bands. The above results were obtained with 50-ms signals, but generally similar data were obtained with a signal duration of 240 ms. The difficulties raised for experimentalists and theorists by such long-term practice effects are discussed.


Sound-power collection by the auditory periphery of the Mongolian gerbil Meriones unguiculatus. I: Middle-ear input impedance. This is the first paper of a series dealing with sound-power collection by the auditory periphery of the gerbil. The purpose of the series is to quantify the physiological action of the gerbil's relatively large tympanic membrane and middle-ear air cavities. To this end the middle-ear input impedance ZT was measured at frequencies between 10 Hz and 18 kHz before and after manipulations of the middle-ear cavity. The frequency dependence of ZT is consistent with that of the middle-ear transfer function computed from extant data. Comparison of the impedance and transfer function suggests a middle-ear transformer ratio of 50 at frequencies below 1 kHz, substantially smaller than the anatomical value of 90 [Lay, J. Morph. 138, 41-120 (1972)]. Below 1 kHz the data suggest a low-frequency acoustic stiffness KT for the middle ear of 970 Pa/mm3 and a stiffness of the middle-ear cavity of 720 Pa/mm3 (middle-ear volume V MEC of 195 mm3); thus the middle-ear air spaces contribute about 70% of the acoustic stiffness of the auditory periphery. Manipulations of a middle-ear model suggest that decreases in V MEC lead to proportionate increases in KT but that further increases in middle-ear cavity volume produce only limited decreases in middle-ear stiffness. The data and the model point out that the real part of the middle-ear impedance at frequencies below 100 Hz is determined primarily by losses within the middle-ear cavity. The measured impedance is comparable in magnitude and frequency dependence to the impedance in several larger mammalian species commonly used in auditory research. A comparison of low-frequency stiffness and anatomical dimensions among several species suggests that the large middle-ear cavities in gerbil act to reduce the middle-ear stiffness at low frequencies. A description of sound-power collection by the gerbil ear requires a description of the function of the external ear.


Using acoustic distortion products to measure the cochlear amplifier gain on the basilar membrane. Most models of the cochlea developed during the last decade have explained frequency selectivity and sensitivity of the cochlea at threshold by the use of power amplification of the acoustic wave on the basilar membrane. This power amplification has been referred to as the cochlear amplifier (CA). In this paper, a method to measure the cochlear amplifier gain as a function of position along the basilar membrane is derived from a simple model. Next, experimental evidence is presented that strongly restricts the properties of these proposed cochlear amplifier models. Specifically, it is shown that small signals generated by mechanical nonlinearities in the basilar membrane motion are not amplified during basilar membrane propagation, contrary to what would be expected from the cochlear amplifier hypotheses. This paper describes a method of measuring the cochlear power gain as a function of frequency and position, from the stapes to within 2 mm of the place corresponding to the frequency being measured. Experimental results in the cat indicate that the total gain of the cochlear amplifier, over the range of positions measured, must be less than 10 dB. The simplest interpretation of the experimental results is that there is no cochlear amplifier. The results suggest that the cochlea must achieve its frequency selectivity by some other means.


Psychometric functions for level discrimination and the effects of signal duration in the goldfish (Carassius auratus): psychophysics and neurophysiology. Classical conditioning of respiration was used to obtain psychometric functions for pulsed tone level discrimination in the goldfish (Carassius auratus). Conditioned respiratory suppression is a graded response that has some properties of a confidence rating measure. These properties were used to obtain receiver operating characteristics (ROC) and psychometric functions using a blocked method of constant stimuli. Empirical ROCs and neurometric functions were also obtained for single auditory-nerve fibers using spike count as the decision variable in order to evaluate a simple rate code for level discrimination. Psychometric and neurometric functions for level discrimination are similar in showing the same general form (summarized by Weibull functions) that is independent of signal duration. The lower slope of neurometric functions compared with behavioral functions for level discrimination is in accord with similar data on sound detection and vision in nonhuman mammals. Both neural and psychophysical level discrimination thresholds decline with increasing duration (20 to 320 ms), with similar slopes except at short signal durations (20 to 50 ms). At these durations, the animal's use of a channel-selection strategy and neural information following stimulus offset could reduce the difference between neural and psychophysical thresholds. The slopes of the neural and psychophysical duration functions are similar to those for human observers, but the majority of auditory-nerve fibers sampled have lower level discrimination thresholds than the behaving animal. Since human observers perform better than the majority of neurons in level discrimination, well-trained human listeners may be able to select channels with superior information, or to combine information across channels in ways that the goldfish and other animals do not. In general, one is encouraged to believe that neural mechanisms need not be more complex or sensitive than those considered here to account for pure-tone level discrimination in fishes, humans, and other vertebrates.


Vowel duration in Afrikaans: the influence of postvocalic consonant voicing and syllable structure. A production study was conducted to investigate the effect of vowel lengthening before voiced obstruents, and the possible influence that the openness versus closedness of syllables have on the temporal structure of vowels in some languages. The results revealed that vowels were significantly longer when followed by voiced consonants than voiceless consonants. Vowel duration did not, however, vary with syllable structure. However, vowels in open syllables followed by [+ voiced] consonants tended to be longer than when the following consonants were [- voiced]. These results are discussed in the context of current knowledge of other languages.


Preliminary results on speaker-dependent variation in the TIMIT database. A set of phonetic studies based on analysis of the TIMIT speech database is presented. Using a database methodological approach, these studies detail new results in speaker-dependent variation due to sex and dialect region of the talker including effects on stop release frequency, speaking rate, vowel reduction, flapping, and the use of glottal stop. TIMIT was found to be fertile ground for gathering acoustic-phonetic knowledge having relevance to the phonetic classification and recognition goals for which TIMIT was designed, as well as to the linguist attempting to describe regularity and variability in the pronunciation of read English speech.


Observations on a principal components analysis of head-related transfer functions. A recent principal components analysis (Kistler and Wightman, 1992) has shown that the transfer functions of the human external ear, for a wide range of source locations, can be expressed as weighted sums of a small number of basis vectors. Directional transfer functions obtained in this laboratory, using substantially different measurement techniques, yielded principal component basis vectors that are remarkably similar to those reported by Kistler and Wightman. When this subject population was divided in half according to the overall physical sizes of subjects, basis vectors computed for the subpopulation of smaller subjects were shifted systematically to higher frequencies relative to those computed for the subpopulation of larger subjects.


Correlation between level of heparinization and patency of the infarct-related coronary artery after treatment of acute myocardial infarction with alteplase (rt-PA). The conjunctive use of intravenous heparin may influence the efficacy of alteplase for coronary thrombolysis in patients with acute myocardial infarction. In this study we examined the relation between the level of intravenous anticoagulation with heparin and sustained coronary artery patency in a subgroup of patients of the European Cooperative Study Group (ECSG) trial. In the ECSG trial, patients treated with alteplase and aspirin were randomized to concomitant fixed doses of intravenous heparin (a bolus dose of 5,000 U followed by a continuous infusion of 1,000 U/h or placebo). The current study group comprised 149 of 324 ECSG patients allocated to heparin therapy and 132 of 320 ECSG patients allocated to placebo administration who had both an interpretable coronary angiogram obtained within 6 days of treatment and sufficient plasma samples to assess the level of anticoagulation. Activated partial thromboplastin times, fibrinogen and D-dimer levels were determined on plasma samples at baseline and at 45 min and 3, 12, 24 and 36 h after the start of alteplase administration. The coronary artery patency rate was higher in patients allocated to heparin therapy than in those allocated to placebo (80% and 71%, respectively, p = 0.05). Patients allocated to heparin were classified into three subgroups: 48 patients (32%) with all activated partial thromboplastin times at least twice their own baseline value (optimal anticoagulation), 40 patients (27%) with the lowest activated partial thromboplastin time at 3, 12, 24 or 36 h between 130% and 200% of the baseline value (suboptimal anticoagulation) and 61 patients with at least one activated partial thromboplastin time less than 130% of baseline (inadequate anticoagulation). In the heparin group, coronary artery patency correlated with the level of anticoagulation: 90%, 80% and 72%, respectively, in patients with optimal, suboptimal and inadequate anticoagulation (p = 0.02, optimal vs. inadequate anticoagulation). Heparin administration was associated with a smaller reduction in fibrinogen and a smaller increase in D-dimer level during and after alteplase administration. No correlation was found between fibrinogen or D-dimer levels and coronary artery patency. No intracerebral hemorrhage occurred in these patients; however, bleeding was more frequent in the subgroup with optimal anticoagulation (p = 0.05). Intense anticoagulation with intravenous heparin enhances coronary artery patency after alteplase treatment of acute myocardial infarction.


PAIMS 2: alteplase combined with heparin versus heparin in the treatment of acute pulmonary embolism. Plasminogen activator Italian multicenter study 2. The effect of alteplase versus heparin in pulmonary embolism has not been studied extensively with serial pulmonary angiograms. The aim of this randomized, open trial was to evaluate the efficacy and safety of alteplase followed by heparin, versus heparin alone, in 36 patients with angiographically documented pulmonary embolism. Twenty patients were allocated randomly to a 2-h infusion of alteplase (10 mg bolus, then 90 mg over 2 h) followed by heparin; the other 16 patients were given intravenous heparin at a continuous infusion rate of 1,750 IU/h. The vascular obstruction, assessed by the Miller index at pulmonary angiography, decreased significantly in alteplase-treated patients (p less than 0.01) from a baseline of 28.3 +/- 2.9 to a value of 24.8 +/- 5.2 2 h after the start of infusion; in the heparin group there was no change (from 25.3 +/- 5.3 to 25.2 +/- 5.4). Mean pulmonary artery pressure decreased significantly from a baseline of 30.2 +/- 7.8 mm Hg to 21.4 +/- 6.7 in the alteplase group and increased in the heparin group (from 22.3 +/- 10.5 to 24.8 +/- 11.2 mm Hg). For a subset of patients, lung scans were performed at baseline and on days 7 and 30. There were no differences between the two groups in the follow-up lung scans, but there were significant decreases from the baseline values. Bleeding occurred in 14 of 20 alteplase-treated patients and in 6 of 16 in the heparin group (p = NS). There were three major bleeding episodes in the alteplase group and two in the heparin group. Two patients died after fibrinolysis (one of acute renal failure after cardiac tamponade and one of cardiac arrest after cerebral hemorrhage) and one patient in the heparin group died of recurrent pulmonary embolism. Alteplase resulted in a greater and faster improvement of the angiographic and hemodynamic variables compared with heparin. However, the high frequency of bleeding observed with alteplase in this trial suggests that patients should be carefully selected before thrombolytic therapy is given.


Antiarrhythmic drug therapy and cardiac mortality in atrial fibrillation. The Stroke Prevention in Atrial Fibrillation Investigators. The relation between cardiac mortality and antiarrhythmic drug administration has not been fully determined. This relation was analyzed in 1,330 patients enrolled in the Stroke Prevention in Atrial Fibrillation Study, a randomized clinical trial comparing warfarin, aspirin and placebo for the prevention of ischemic stroke or systemic embolism in patients with nonvalvular atrial fibrillation. Patients who received antiarrhythmic drug therapy for atrial fibrillation in this study were compared with patients not receiving antiarrhythmic agents. The relative risk of cardiac mortality, including arrhythmic death, in patients receiving antiarrhythmic drug therapy was determined and adjusted for other cardiac risk factors. In patients receiving antiarrhythmic drug therapy, cardiac mortality was increased 2.5-fold (p = 0.006, 95% confidence interval [CI] 1.3 to 4.9) and arrhythmic death was increased 2.6-fold (p = 0.02, 95% CI 1.2 to 5.6). Among patients with a history of congestive heart failure, those given antiarrhythmic medications had a relative risk of cardiac death of 4.7 (p less than 0.001, 95% CI 1.9 to 11.6) compared with that of patients not so treated; the relative risk of arrhythmic death in the treated group was 3.7 (p = 0.01, 95% CI 1.3 to 10.4). Patients without a history of congestive heart failure had no increased risk of cardiac mortality (relative risk 0.70, 95% CI 0.2 to 3.1) during antiarrhythmic drug therapy. After exclusion of 23 patients with documented ventricular arrhythmias and adjustment for other variables predictive of cardiac death, patients receiving antiarrhythmic drugs were not at increased risk of cardiac death or arrhythmic death. However, in patients with a history of heart failure who received antiarrhythmic drug therapy, the relative risk of cardiac death was 3.3 (p = 0.05, 95% CI 0.99 to 11.1) and that of arrhythmic death was 5.8 (p = 0.009, 95% CI 1.5 to 21.7) compared with the risk in patients not taking antiarrhythmic medications. Although antiarrhythmic drug therapy was not randomly determined in this trial, the data suggest that in patients with atrial fibrillation and a history of congestive heart failure, the risk of such therapy may outweigh the potential benefit of maintaining sinus rhythm.


Incidence and prognostic implications of heart block complicating inferior myocardial infarction treated with thrombolytic therapy: results from TIMI II. The aim of this study was to determine the incidence and significance of second- or third-degree heart block among patients with inferior myocardial infarction treated with thrombolytic therapy. Data from the prethrombolytic era suggest that heart block occurs in approximately 20% of patients with acute inferior myocardial infarction and is associated with a marked increase in mortality. Little is known about the incidence and prognostic implications of heart block among patients receiving thrombolytic therapy. We studied 1,786 patients with acute inferior myocardial infarction enrolled in the Thrombolysis in Myocardial Infarction (TIMI) II Trial who received recombinant tissue-type plasminogen activator (rt-PA) within 4 h of the onset of symptoms. Heart block occurred in 214 patients (12%); 113 (6.3%) had heart block on presentation and 101 (5.7%) developed heart block in the 24 h after treatment with rt-PA. Patients with heart block at entry were slightly older and a greater proportion had cardiogenic shock. The 21-day mortality rate among patients with heart block at entry was 7.1% (8 of 113), compared with 2.7% (45 of 1,673) among patients without heart block at study entry (relative risk 2.6, p = 0.007). However, heart block was not independently associated with 21-day mortality after adjustment for other variables, including shock. Mortality and other adverse cardiac events in the following year were similar among patients with and without heart block. Among patients without heart block at study entry, coronary angiography among patients randomly assigned to coronary catheterization 18 to 48 h after admission revealed that the infarct-related artery was occluded in 28.2% (11 of 39) of patients who developed heart block versus 15.5% (112 of 723) of patients without heart block (p = 0.04). The 21-day mortality rate was increased among patients in whom heart block developed after thrombolytic therapy (9.9% [10 of 101] versus 2.2% [35 of 1,572] of patients without heart block, relative risk 4.5, p less than 0.001). Analysis of the increased mortality among patients who developed heart block suggests that mortality was due to severe cardiac dysfunction; no patient was considered to have died as a result of the heart block or its treatment. Heart block is common among patients with inferior infarction given thrombolytic therapy and is associated with increased mortality. These clinical and anatomic data provide insight into the mechanism of heart block and increased mortality among such patients.


Propafenone-mexiletine combination for the treatment of sustained ventricular tachycardia. The purpose of this study was to explore the efficacy of combined therapy with propafenone and mexiletine for control of sustained ventricular tachycardia. Combination antiarrhythmic drug therapy may enhance efficacy and lead to control of ventricular arrhythmias in some patients. Few reports have studied the combination of class IB and class IC drugs. Thus, this study was designed to investigate a combination of mexiletine and propafenone in patients with refractory ventricular tachycardia. Sixteen patients with sustained ventricular tachycardia had their clinical arrhythmia induced by programmed stimulation. Procainamide and propafenone alone failed to prevent reinduction of tachycardia in all. Mexiletine was subsequently added to propafenone and programmed stimulation was repeated. With combination therapy ventricular tachycardia was noninducible in three patients (19%). A fourth who had presented with polymorphic ventricular tachycardia had slow bundle branch reentry (cycle length 500 ms) induced. In the other 12, tachycardia cycle length increased from 262 +/- 60 ms at baseline to 350 +/- 82 ms with propafenone and to 390 +/- 80 ms with propafenone plus mexiletine (p less than 0.0001 compared with baseline). Hemodynamic deterioration requiring defibrillation occurred in six patients at baseline study, in five taking propafenone and in two taking both drugs. The combination of propafenone and mexiletine is effective in suppressing the induction of ventricular tachycardia in some patients refractory to procainamide and propafenone alone. In those in whom ventricular tachycardia could still be induced, the rate was slower and hemodynamically tolerated.


Comparison of 24-hour parasympathetic activity in endurance-trained and untrained young men. This study compares 24-h parasympathetic activity in aerobically trained and untrained healthy young men. Higher values of parasympathetic nervous system activity are associated with a low mortality rate in patients after myocardial infarction, but it remains uncertain what therapeutic interventions can be used to increase parasympathetic activity. Although it is thought that exercise training can increase parasympathetic activity, studies have reported conflicting results, perhaps because this variable was measured for only brief intervals and usually inferred from changes in reflex responses induced by pharmacologic blockade. Parasympathetic activity was assessed noninvasively from 24-h ECG recordings by calculating high frequency (0.15 to 0.40 Hz) beat to beat heart period variability in eight endurance-trained men (maximal oxygen consumption greater than or equal to 55 ml/kg per min) and eight age-matched (mean = 29 yr) untrained men (maximal oxygen consumption less than or equal to 40 ml/kg per min). The data were analyzed separately for sleeping hours when parasympathetic activity is dominant and also for waking hours. The geometric mean of high frequency power was greater in the trained than in the untrained men during the day (852 vs. 177 ms2, p less than 0.005), during the night (1,874 vs. 427 ms2, p less than 0.005) and over the entire 24 h (1,165 vs. 276 ms2, p less than 0.001). Parasympathetic activity is substantially greater in trained than in untrained men, and this effect is present during both waking and sleeping hours. These data suggest that exercise training may increase parasympathetic activity over the entire day and may therefore prove to be a useful adjunct or alternative to drug therapy in lessening the derangements of autonomic balance found in many cardiovascular diseases.


Clinical outcome of patients with advanced coronary artery disease after viability studies with positron emission tomography. The aim of this study was to determine the prognostic significance of perfusion-metabolism imaging in patients undergoing positron emission tomography for myocardial viability assessment. Positron emission tomography using nitrogen-13 ammonia and 18fluorodeoxyglucose to assess myocardial blood flow and metabolism has been shown to predict improvement in wall motion after coronary artery revascularization. The prognostic implications of metabolic imaging in patients with advanced coronary artery disease have not been investigated. Eighty-two patients with advanced coronary artery disease and impaired left ventricular function underwent positron emission tomographic imaging between August 1988 and March 1990 to assess myocardial viability before coronary artery revascularization. Forty patients underwent successful revascularization. Patients who exhibited evidence of metabolically compromised myocardium by positron emission tomography (decreased blood flow with preserved metabolism) who did not undergo subsequent revascularization were more likely to experience a myocardial infarction, death, cardiac arrest or late revascularization due to development of new symptoms than were the other patient groups (p less than 0.01). Concordantly decreased flow and metabolism in segments of previous infarction did not affect outcome in patients with or without subsequent revascularization. Those with a compromised myocardium who did undergo revascularization were more likely to experience an improvement in functional class than were patients with preoperative positron emission tomographic findings of concordant decrease in flow and metabolism. Positron emission tomographic myocardial viability imaging appears to identify patients at increased risk of having an adverse cardiac event or death. Patients with impaired left ventricular function and positron emission tomographic evidence for jeopardized myocardium appear to have the most benefit from a revascularization procedure.


Functional recovery after coronary revascularization for chronic coronary artery disease is dependent on maintenance of oxidative metabolism. This study was performed to define the importance of maintenance of oxidative metabolism as a descriptor and determinant of functional recovery after revascularization in patients with left ventricular dysfunction attributable to chronic coronary artery disease. Although myocardial accumulation of 18F-fluorodeoxyglucose indicates the presence of tissue that is metabolically active, it may not identify those metabolic processes required for restoration of myocardial contractility. Experimental studies suggest that, under conditions of ischemia and reperfusion, maintenance of myocardial oxidative metabolism is an important metabolic determinant of the capacity for functional recovery. In 16 patients positron emission tomography was performed to characterize myocardial perfusion (with H(2)15O), oxidative metabolism (with 11C-acetate) and utilization of glucose (with 18F-fluorodeoxyglucose). Dysfunctional but viable myocardium was differentiated from nonviable myocardium on the basis of assessments of regional function before and after coronary revascularization. To define the importance of coronary revascularization on myocardial perfusion and metabolism, tomography was repeated in 11 patients after revascularization. Before revascularization, perfusion in 24 dysfunctional but viable myocardial segments and 29 nonviable segments averaged 79% and 74%, respectively, of that in 42 normal myocardial segments (both p less than 0.01). Dysfunctional but viable myocardium exhibited oxidative metabolism comparable to that in normal myocardium. In contrast, in nonviable myocardium, oxidative metabolism was only 66% of that in normal (p less than 0.01) and 69% of that in reversibly dysfunctional myocardium (p less than 0.003). Regional utilization of glucose normalized to regional perfusion in dysfunctional but viable myocardium was greater than that in normal myocardium (p less than 0.01). However, in both reversibly and persistently dysfunctional myocardium, utilization of glucose normalized to relative perfusion was markedly variable. The results indicate that preservation of oxidative metabolism is a necessary condition for recovery of function after coronary recanalization in patients with chronic coronary artery disease. Consequently, approaches that measure myocardial oxygen consumption, such as dynamic positron emission tomography with 11C-acetate, should facilitate the identification of those patients most likely to benefit from coronary revascularization.


Improved myocardial ischemic response and enhanced collateral circulation with long repetitive coronary occlusion during angioplasty: a prospective study. The goal of the study was to evaluate the progressive increase in ischemic threshold with multiple sequential transient coronary occlusions and to assess the role of the collateral circulation in adaptation to ischemia. It has been observed that the duration of balloon inflations during coronary angioplasty can be gradually prolonged during subsequent dilations with a reduction in patient symptoms and diminished ischemic electrocardiographic (ECG) changes. Although the mechanism has not been fully explained, recruitment of coronary collateral circulation induced by repeated coronary occlusion has been reported. The stimuli for recruitment and the natural history of coronary collateral circulation are not understood. Seventeen patients with isolated stenosis of the left anterior descending coronary artery and a normal left ventricle were enrolled. Angioplasty consisted of five successive prolonged inflations. Sequential changes in clinical, intracoronary ECG and left ventricular indexes of myocardial ischemia were examined. Coronary collateral channels were evaluated during balloon inflations by ipsilateral and contralateral injections of contrast medium and hemodynamically by occlusion pressure. An improved tolerance to myocardial ischemia with repetitive coronary occlusions was demonstrated by a significant reduction of angina, ST segment deviation, left ventricular filling pressure and less impairment of ejection fraction. Left ventricular wall motion abnormalities remained unchanged. Collateral angiographic grade did not change in 7 patients and increased in 10. This study confirms a progressive adaptation of myocardial ischemia to repetitive coronary occlusions and supports the concept that sequential episodes of myocardial ischemia are a stimulating factor for the recruitment of collateral channels in humans. These results also suggest that enhancement of recruitable collateral circulation might be an underlying mechanism of myocardial ischemic preconditioning.


Effects of converting enzyme inhibition on baroreflex sensitivity in patients with myocardial infarction. Baroreflex sensitivity provides useful prognostic information in patients after acute myocardial infarction. However, no data are available about the effects of converting enzyme inhibition on this variable. The aim of the study was to evaluate the effects of angiotensin-converting enzyme inhibition on baroreflex sensitivity in patients after uncomplicated myocardial infarction. Twenty-five patients after uncomplicated myocardial infarction underwent baroreflex sensitivity evaluation 72 to 96 h after symptom onset and after 4 days of captopril therapy. Twenty additional patients with the same characteristics were evaluated at the same time intervals before and after placebo administration to identify spontaneous baroreflex sensitivity variations. Baroreflex sensitivity was assessed by calculating the regression line relating phenylephrine-induced increases in systolic blood pressure to the attendant changes in the RR interval. The mean baroreflex sensitivity value increased after captopril administration from 6.5 +/- 4.2 to 11.8 +/- 6.1 ms/mm Hg (p less than 0.01) and in individual analyses increased by greater than 2 ms/mm Hg in 68% of patients. Mean plasma renin activity increased after captopril from 3.7 +/- 2.4 to 8.5 +/- 4.9 ng/ml per h (p less than 0.005). No difference was detectable in baroreflex sensitivity and plasma renin activity values according to the site of necrosis. In the control group, baroreflex sensitivity and plasma renin activity remained unchanged between the two studies. This study demonstrates that in patients with uncomplicated myocardial infarction, captopril significantly improves the chronotropic response to baroreceptor stimulation.


Prospective analysis of possible myocardial damage or hemolysis occurring as a result of prolonged autoperfusion angioplasty in humans. The purpose of this study was to further explore the procedural safety of prolonged (15-min) dilation using an autoperfusion coronary angioplasty balloon by assessing the degree of myocardial damage or hemolysis, if any, occurring as a result of the procedure. Prolonged balloon inflation periods may be beneficial during percutaneous transluminal coronary angioplasty. The duration of standard balloon angioplasty is often limited by the occurrence of myocardial ischemia due to loss of anterograde blood flow. Autoperfusion angioplasty allows continued myocardial perfusion during balloon inflation and has previously been shown to reduce but not totally eliminate acute myocardial ischemia during prolonged (up to 15 min) balloon inflation. The risk of intravascular hemolysis as a result of autoperfusion angioplasty has not yet been fully delineated. Sixty-two consecutive patients (76% men; mean age 58 years) undergoing elective percutaneous transluminal coronary angioplasty of a single lesion were studied. Serial electrocardiographic and creatine kinase MB isoenzyme data were examined to detect evidence of myocardial damage. Tests for hemolysis (plasma free hemoglobin, serum haptoglobin and serum lactate dehydrogenase) were obtained in the 1st 24 consecutive patients. Inflation time was 14 +/- 4 min (mean +/- SD) and the procedure was successful (less than or equal to 50% residual lesion stenosis) in 59 patients (95%). Electrocardiographic evidence of myocardial infarction (greater than 1 mm persistent ST segment depression, greater than 1 mm ST segment elevation or new Q waves) was not observed in any patient. Cardiac enzyme assays were within the normal range in all patients. No evidence of hemolysis was found in the 24 consecutive patients studied. We conclude that prolonged autoperfusion angioplasty can be performed in patients without clinical evidence of myocardial damage or hemolysis.


Intraoperative evaluation of mitral valve regurgitation and repair by transesophageal echocardiography: incidence and significance of systolic anterior motion. This study was designed to delineate the utility and results of intraoperative transesophageal echocardiography in the evaluation of patients undergoing mitral valve repair for mitral regurgitation. Mitral valve reconstruction offers many advantages over prosthetic valve replacement. Intraoperative assessment of valve competence after repair is vital to the effectiveness of this procedure. Intraoperative transesophageal echocardiography was performed in 143 patients undergoing mitral valve repair over a period of 23 months. Before and after repair, the functional morphology of the mitral apparatus was defined by two-dimensional echocardiography; Doppler color flow imaging was used to clarify the mechanism of mitral regurgitation and to semiquantitate its severity. There was significant improvement in the mean mitral regurgitation grade by composite intraoperative transesophageal echocardiography after valve repair (3.6 +/- 0.8 to 0.7 +/- 0.7; p less than 0.00001). Excellent results from initial repair with grade less than or equal to 1 residual mitral regurgitation were observed in 88.1% of patients. Significant residual mitral regurgitation (grade greater than or equal to 3) was identified in 11 patients (7.7%); 5 underwent prosthetic valve replacement, 5 had revision of the initial repair and 1 patient had observation only. Of the 100 patients with a myxomatous mitral valve, the risk of grade greater than or equal to 3 mitral regurgitation after initial repair was 1.7% in patients with isolated posterior leaflet disease compared with 22.5% in patients with anterior or bileaflet disease. Severe systolic anterior motion of the mitral apparatus causing grade 2 to 4 mitral regurgitation was present in 13 patients (9.1%) after cardiopulmonary bypass. In 8 patients (5.6%), systolic anterior motion resolved immediately with correction of hyperdynamic hemodynamic status, resulting in grade less than or equal to 1 residual mitral regurgitation without further operative intervention. Transthoracic echocardiography before hospital discharge demonstrated grade less than or equal to 1 residual mitral regurgitation in 86.4% of 132 patients studied. A significant discrepancy (greater than 1 grade) in residual mitral regurgitation by predischarge transthoracic versus intraoperative transesophageal echocardiography was noted in 17 patients (12.9%). Transesophageal echocardiography is a valuable adjunct in the intraoperative assessment of mitral valve repair.


Nonsurgical closure of femoral pseudoaneurysms complicating cardiac catheterization and percutaneous transluminal coronary angioplasty. This study was performed to describe the initial experience and follow-up of ultrasound-guided compression of pseudoaneurysms in patients receiving systemic anticoagulant or antiplatelet therapy, or both, after recent cardiac catheterization or percutaneous transluminal coronary angioplasty. Femoral artery pseudoaneurysm formation after an interventional procedure is becoming more common as larger caliber catheters and prolonged anticoagulant and antiplatelet therapy are being used. Traditional treatment of this complication has been surgical repair. This study describes a new method of closing femoral pseudoaneurysms by using external compression guided by Doppler color flow imaging. Fifteen patients, 3 undergoing cardiac catheterization and 12 undergoing coronary angioplasty, developed an expansile groin mass at the vascular access site diagnosed as a femoral artery pseudoaneurysm by Doppler ultrasound. Seven of the patients had undergone coronary stenting and were receiving postprocedural anticoagulant therapy. These patients underwent progressive graded mechanical (C-clamp) external compression guided by ultrasound. The mechanical compression was titrated to obliterate the vascular tracts to these aneurysms and maintain adequate flow in the femoral artery. After an average compression time of 30 min (range 10 to 120), these tracts remained closed. Follow-up ultrasound examination at 24 h or later confirmed continued closure in all. This study suggests that nonsurgical closure of femoral pseudoaneurysms is feasible. This technique may be valuable in managing vascular access-related complications after diagnostic and interventional procedures, even in patients requiring prolonged anticoagulant therapy.


Effects of diuretic therapy on the development of tolerance during continuous therapy with nitroglycerin. This study examined the effects of concurrent diuretic therapy on the hemodynamic responses to short-term and sustained therapy with transdermal nitroglycerin. Sodium retention and plasma volume expansion occur during therapy with nitroglycerin and may play a role in the loss of nitroglycerin effects during sustained therapy. Twenty-two normal male volunteers were treated for 1 week with either hydrochlorothiazide and amiloride (50 + 5 mg) (n = 11) or placebo (n = 11) in a randomized, double-blind fashion. All 22 subjects then received continuous transdermal nitroglycerin (19 +/- 1 mg/24 h) for 5 to 7 days. On the first and last day of transdermal nitroglycerin therapy, standing heart rate, systolic blood pressure and hematocrit values were assessed at 8, 9 and 10 AM and 12 noon. Heart rate and blood pressure responses to sublingual nitroglycerin (0.6 mg) were also evaluated before and after sustained transdermal nitroglycerin therapy. A significant loss of the hemodynamic effects of transdermal and sublingual nitroglycerin occurred during sustained therapy in both the diuretic and placebo therapy groups. In both groups, transdermal nitroglycerin therapy was associated with a significant decrease in hematocrit that persisted for the entire treatment period. These results suggest that diuretic therapy does not prevent plasma volume expansion or the loss of hemodynamic effects during sustained transdermal nitroglycerin therapy. The persistent decrease in hematocrit suggests that plasma volume expansion plays a role in the attenuation of nitrate effects. It also provides evidence of continued vascular activity of nitroglycerin despite loss of systemic hemodynamic effects.


Restenosis after directional coronary atherectomy. This study evaluates the incidence of restenosis after successful directional coronary atherectomy and identifies risk factors for restenosis. Directional coronary atherectomy has been shown to be a safe and effective treatment of obstructive coronary artery disease; however, information regarding restenosis is limited. Between October 1986 and December 1989, 289 patients with 332 lesions were successfully treated with directional coronary atherectomy and followed up prospectively. Clinical follow-up information was available for 98% and angiographic follow-up information was obtained for 82% at approximately 6 months, or earlier if symptoms recurred. Angiograms were quantitatively analyzed. Restenosis was defined as greater than 50% stenosis at the site of intervention. Seventy-four percent of patients were either asymptomatic or clinically improved after the procedure. Thirty-two percent were subsequently treated by coronary artery bypass surgery (14%), percutaneous transluminal coronary angioplasty (4%) or repeat atherectomy (13%). Angiographic evidence of restenosis was observed in 42%. The restenosis rate in native coronary arteries was 31% for primary lesions and 28% and 49%, respectively, for lesions treated with one or two previous angioplasty procedures. The restenosis rate for saphenous vein grafts was 53% for primary lesions and 58% and 82%, respectively, for lesions treated with one or two previous angioplasty procedures. The median interval to angiographically documented restenosis was 133 days. A higher restenosis rate was associated with a saphenous vein graft, hypertension, a longer lesion (greater than or equal to 10 mm), a smaller vessel diameter (less than 3 mm), a noncalcified lesion and use of a smaller (6F) device. Restenosis remains a limitation of directional coronary atherectomy. A subset of patients with larger vessels, shorter lesions or lesions treated with a larger (7F) device may have a more favorable outcome.


Natural history of sinus node disease treated with atrial pacing in 213 patients: implications for selection of stimulation mode. This study was designed to analyze the incidence and determinants of complications and long-term survival in sinus node disease treated with atrial pacing. Knowledge of the natural history of sinus node disease treated with different pacing modes is imperfect, and controversy exists regarding the optimal pacemaker therapy. A consecutive series of 213 patients with sinus node disease initially treated with atrial pacing was studied for a median follow-up period of 60 months. The end points studied were permanent atrial fibrillation, high grade atrioventricular (AV) block, P wave undersensing, pacing mode change, reoperation and death. Several prognostic factors were evaluated statistically and the survival rate was compared with that of a matched general population. The incidence rate of permanent atrial fibrillation during follow-up was 7% (1.4%/year). The risk of this arrhythmia increased substantially with age greater than or equal to 70 years at pacemaker implantation. Only 2 of the 15 patients who developed permanent atrial fibrillation required ventricular pacing. High grade AV block occurred in 8.5% (1.8%/year) and its incidence was much greater in patients with complete bundle branch block or bifascicular block (35%) than in patients without such conduction disturbances (6%). A change to ventricular or dual-chamber stimulation was necessary in 14% of all patients, primarily because of early lead dislodgment or high grade AV block. Surgical intervention with maintenance of atrial pacing was required in 7% of patients. The survival rates of 97% at 1 year, 89% at 5 years and 72% at 10 years did not differ significantly from those of a matched general population. In sinus node disease, atrial pacing can be successfully applied during long-term follow-up. Patients with complete bundle branch or bifascicular block in addition to sinus node disease should initially receive a dual-chamber pacemaker, but routine application of dual-chamber stimulation does not appear to be warranted.


Sudden cardiac death associated with isolated congenital coronary artery anomalies. Congenital coronary anomalies are associated with sudden death and exercise-related death. Clarification of the risk and mechanisms of sudden death in patients with coronary anomalies may aid in decisions on intervention. The clinicopathologic records of 242 patients with isolated coronary artery anomalies were reviewed for information on mode of death and abnormalities of the initial segment (acute angle takeoff, valvelike ridges or aortic intramural segments) and course of the anomalous coronary artery. Cardiac death occurred in 142 patients (59%); 78 (32%) of these deaths occurred suddenly. Of sudden deaths, 45% occurred with exercise. Sudden death (28 of 49, 57%) and exercise-related death (18 of 28, 64%) were most common with origin of the left main coronary artery from the right coronary sinus. Anomalous origin of the right coronary artery from the left coronary sinus was also commonly associated with exercise-related sudden death (6 of 13 sudden deaths, 46%). High risk anatomy involved abnormalities of the initial coronary artery segment or coursing of the anomalous artery between the pulmonary artery and aorta. Younger patients (less than or equal to 30 years old) were significantly more likely than older patients (greater than or equal to 30 years old) to die suddenly (62% vs. 12%, p = 0.0001) or during exercise (40% vs. 2%, p = 0.00001) despite their low frequency of significant atherosclerotic coronary artery disease (1% vs. 40%, p = 0.00001). Younger patients (less than or equal to 30 years old) with an isolated coronary artery anomaly are at risk of dying suddenly and with exercise. Therefore, greater effort for early detection and surgical repair of these lesions is warranted.


Ventricular tachycardia after surgical repair of tetralogy of Fallot: results of intraoperative mapping studies. Four patients with previous repair of tetralogy of Fallot and ventricular tachycardia underwent map-guided surgery to ablate the arrhythmias. Although patients with repaired tetralogy of Fallot are at increased risk of sudden death due to ventricular tachycardia, little is known of the origin and mechanism of this arrhythmia. A customized right ventricular balloon with 112 electrodes was used to record endocardial activation and, where possible, simultaneous epicardial recordings were obtained with a sock electrode array. Three patients had an aneurysm of the right ventricular outflow tract and one had a septal aneurysm. All had moderate to severe pulmonary valve insufficiency. Preoperative electrophysiologic study demonstrated inducible rapid (cycle length 180 to 300 ms) hemodynamically unstable monoform ventricular tachycardias. Intraoperatively, five different tachycardias (two in one patient) were induced and mapped. The sites of earliest activation were located in the subendocardium of the right ventricular outflow tract in all, but they varied widely among the septum, free wall and parietal band and could not be identified by visible scar. All were due to a macroreentrant circuit initiated by a critical delay in activation beyond a functional arc of block. Two patients treated by cryoablation while the heart was beating and perfused at normal temperature had inducible ventricular tachycardia postoperatively. In the two subsequent patients, the application of cryoablation under anoxic cardiac arrest resulted in noninducibility of arrhythmia. Ventricular tachycardia in tetralogy of Fallot in these four patients was caused by macroreentry in the right ventricular outflow tract. Surgical success depends on detailed mapping and cryoablation under anoxic cardiac arrest. In patients at risk of sudden death, map-directed surgery may offer distinct advantages over either implantable devices or drug therapy.


Characteristics of local electrogram predicting successful transcatheter radiofrequency ablation of left-sided accessory pathways. The purpose of this study was to analyze and compare the local electrograms recorded at successful and unsuccessful sites of ablation to identify the criteria that may predict successful sites and minimize unnecessary radiofrequency delivery. Transcatheter ablation of accessory pathways using radiofrequency energy requires extremely precise localization of an accessory pathway. Local electrograms from 50 consecutive patients with left-sided accessory pathways who underwent transcatheter radiofrequency ablation were analyzed. During catheter ablation, localization of accessory pathways was performed in 39 pathways during pre-excited sinus rhythm and in 14 pathways during orthodromic tachycardia. A total of 429 local electrograms at target sites obtained before delivery of radiofrequency current was analyzed. A prospective study was performed in another 20 patients using the criteria derived from the retrospective study. Accessory pathway conduction block was achieved in 36 (92%) of 39 pathways in which mapping was performed during pre-excited sinus rhythm and in 9 (64%) of 14 pathways in which mapping was performed during orthodromic tachycardia (p less than 0.05). When mapping was performed during pre-excited sinus rhythm, a combination of four variables (that is, an accessory pathway potential, stability of local electrograms, atrial activation greater than 1 mV and ventricular activation preceding the onset of the delta wave) showed a 62% probability of success. In contrast, excluding these variables resulted in a 95% probability of failure (noneffective or transiently effective). The prospective study shows that the use of these criteria can significantly reduce the number of current applications. When mapping was performed during orthodromic tachycardia, recording the earliest atrial activation was the most powerful predictor of success. A stable local electrogram with a small notch on the ventricular potential, presumed to be an accessory pathway potential, may add predictive value. Transcatheter radiofrequency ablation is highly effective in the treatment of patients with left-sided accessory pathways. Specific characteristics of local electrograms can be important predictors of success or failure. Mapping during pre-excited rhythm renders ablation more effective than does mapping during orthodromic tachycardia.


Clinical characteristics and electrophysiologic properties of atrioventricular accessory pathways: importance of the accessory pathway location. This study was designed to assess the influence of accessory atrioventricular (AV) pathway location on the clinical and electrophysiologic characteristics of 384 consecutive symptomatic patients having a single accessory pathway. Four locations were studied: left free wall (n = 270), posteroseptal (n = 52), anteroseptal (n = 29) and right free wall (n = 33). Ten clinical variables and 12 electrophysiologic variables were analyzed, including the effective refractory period of the accessory pathway and the different clinically occurring and inducible arrhythmias. Only two clinical findings were associated with accessory pathway location: 1) later age at onset of symptoms in the left free wall versus other accessory pathway locations (24 +/- 12 vs. 20 +/- 11 years, p = 0.02), and 2) later age at the time of electrophysiologic study in the left free wall accessory pathway location (36 +/- 13 vs. 32 +/- 11 years, p = 0.01). Six electrophysiologic variables showed a correlation with the accessory pathway location: 1) retrograde conduction only was found less frequently in right free wall (9%) and anteroseptal (10%) than in left free wall (26%) and posteroseptal (29%) accessory pathway locations (p = 0.05); 2) the retrograde effective refractory period of the accessory pathway was shorter in anteroseptal (253 +/- 52 ms) and left free wall (270 +/- 72 ms) as compared with right free wall (296 +/- 101 ms) and posteroseptal (301 +/- 76 ms) locations (p = 0.05); 3) retrograde decremental conduction over the accessory pathway was present in the posteroseptal (17%) and left free wall (3%) but absent in the other locations (p less than 0.001); 4) anterograde decremental conduction was only seen in the right free wall location (12%) (p less than 0.001); 5) orthodromic reentrant tachycardia was induced less frequently in the right free wall than in other locations (70% vs. 93%, p less than 0.001); and 6) inducibility of atrial fibrillation was greater in anteroseptal (62%) than in right free wall (21%), left free wall (44%) and posteroseptal (36%) locations (p = 0.01). The location of the accessory AV pathway is associated with specific electrophysiologic characteristics.


Parathyroid hormone responses to marked hypocalcemia in infants and young children undergoing repair of congenital heart disease. The integrity of the parathyroid axis was tested in 18 infants and young children undergoing repair of congenital heart disease with cardiopulmonary bypass. Infants are believed to have an immature parathyroid hormone response to hypocalcemia. Whereas adults are known to respond appropriately to hypocalcemia during cardiopulmonary bypass, children have not been studied carefully. Calcium, magnesium, parathyroid hormone, phosphate and total protein were measured in blood samples withdrawn at defined times before, during and after cardiopulmonary bypass. At the initiation of cardiopulmonary bypass, ionized calcium decreased markedly in 12 infants less than or equal to 24 months old (mean +/- SEM 1.11 +/- 0.04 to 0.29 +/- 0.05 mM) and decreased significantly in 6 young children greater than 24 months old (1.19 +/- 0.02 to 0.42 +/- 0.12 mM). In response to hypocalcemia, parathyroid hormone concentration increased significantly in both the infants (from 42 +/- 8 to 103 +/- 29 and 85 +/- 22 pg/ml) and the young children (from 39 +/- 8 to 44 +/- 20 and 92 +/- 30 pg/ml). Before separation from cardiopulmonary bypass, increased parathyroid hormone concentration restored ionized calcium concentration to 0.75 +/- 0.03 mM in the infants and to 0.92 +/- 0.07 mM in the young children. There was no significant influence of either age or the use of deep hypothermia and circulatory arrest on either calcium or parathyroid hormone responses. Total magnesium and total protein concentrations decreased on initiation of cardiopulmonary bypass and thereafter remained stable. Phosphate concentrations were unchanged during the study. In infants and young children undergoing cardiac surgery, the parathyroid hormone response to both hypocalcemia and to rising ionized calcium concentrations was at least as great as that of adults. Thus, the calcium-parathyroid-vitamin D axis functions in infants and young children as it does in adults.


Mechanisms of balloon angioplasty and directional coronary atherectomy as assessed by intracoronary ultrasound. This study was designed to use intracoronary ultrasound imaging to elucidate the physical effects of balloon angioplasty and directional coronary atherectomy in vivo in humans. The proposed mechanisms of coronary artery interventions such as balloon angioplasty and directional atherectomy are based on animal studies or pathologic findings and these data may not be applicable to living patients. Intracoronary ultrasound findings correlate highly with pathologic results and may allow in vivo assessment of the mechanisms of such interventions in humans. Intracoronary ultrasound imaging was performed in 45 patients after a successful coronary intervention (balloon angioplasty in 30, directional coronary atherectomy in 15). Ultrasound images obtained at the treatment site and at an adjacent angiographically normal references site were analyzed quantitatively for minimal lumen diameter, cross-sectional lumen area, are enclosed by the internal elastic lamina, plaque area (internal elastic lamina area--lumen area) and percent area stenosis (plaque area/internal elastic lamina area). Qualitative analysis included assessment of presence of dissection, plaque composition and plaque topography. The results of the two procedures were similar with respect to minimal lumen diameter (angioplasty 2.6 +/- 0.5 vs. atherectomy 2.6 +/- 0.3 mm, p = NS), lumen area (0.07 +/- 0.03 vs. 0.07 +/- 0.02 cm2, p = NS) and percent area stenosis (59 +/- 14% vs. 51 +/- 21%, p = NS). However, after angioplasty, the internal elastic lamina area was significantly larger at the treated site than at the reference site (delta = +0.03 +/- 0.04 cm2, p = 0.01). There was no significant difference between the two sites after atherectomy (delta = -0.01 +/- 0.05 cm2, p = NS). In addition, dissection was seen significantly more often after balloon angioplasty than after atherectomy (50% vs. 7%, p less than 0.01). The results were similar when stratified for plaque composition and morphology. These data were confirmed in six additional patients who underwent ultrasound imaging before and after the intervention. Thus, the improvement in lumen dimensions after coronary balloon angioplasty is a result of both vessel stretch, demonstrated by a larger internal elastic lamina area at the treated site, and dissection. Both vessel stretch and dissection are uncommon after atherectomy, a finding consistent with plaque removal as the major mechanism for improved lumen area after this procedure.