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Biomedical subjects

C T Lewis

Publications and source records attributed to C T Lewis.

At least 19 recordsLinked to original sources

Synchronization of chaotic oscillations in doped fiber ring lasers.

The synchronization of chaotic rare-earth-doped fiber ring lasers is analyzed. The lasers are first coupled by transmitting a fraction c of the circulating electric field in the transmitter and injecting it into the optical cavity of the receiver. A coupling strategy which relies on modulation of the intensity of the light alone is also examined. Synchronization is studied as a function of the coupling strength, and we see excellent synchronization, even with very small c. We prove that in an open loop configuration (c=1) synchronization is guaranteed due to the particular structure of our equations and of the injection method we use. The generalized synchronization of these model lasers is examined when there is parameter mismatch between the transmitter and receiver lasers. The synchronization is found to be insensitive to a wide range of mismatch in laser parameters, but it is sensitive to other parameters, in particular those associated with the phase and the polarization of the circulating electric field. Communicating information between the transmitter and receiver lasers is also addressed. We investigate a scheme for modulating information onto the chaotic electric field and then demodulating and detecting the information embedded in the chaotic signal passed down the communications channel. We show full recovery with very low error for a wide range of coupling strengths.

Journal Article↗

Structure-based design of novel, urea-containing FKBP12 inhibitors.

The structure-based design and subsequent chemical synthesis of novel, urea-containing FKBP12 inhibitors are described. These compounds are shown to disrupt the cis-trans peptidylprolyl isomerase activity of FKBP12 with inhibition constants (Ki,app) approaching 0.10 microM. Analyses of several X-ray crystal structures of FKBP12-urea complexes demonstrate that the urea-containing inhibitors associate with FKBP12 in a manner that is similar to, but significantly different from, that observed for the natural product FK506.

Amino Acid Isomerases↗

Prenatal care in the United States, 1980-94.

OBJECTIVES: This report examines trends in timing of prenatal care in the United States from 1980 to 1994. Demographic characteristics examined include age, race, Hispanic origin, marital status, place of birth of mother, educational attainment of mother, and live-birth order. Social characteristics discussed include barriers to care and pregnancy wantedness. METHODS: The source of data for trends and demographic analysis is the certificate of live birth filed for each child born in the United States. Data for social characteristics are from the 1988 National Maternal and Infant Health Survey (NMIHS). Data from the NMIHS are based on 9,953 responses. RESULTS: Very few groups of women have yet to achieve the goal of 90 percent initiating prenatal care in the first trimester as set by Healthy People 2000. In 1994, 80 percent of all mothers initiated care in the first trimester. Cuban mothers were the only mothers to reach the objective of 90 percent with Japanese mothers close behind at 89 percent. Mothers with the lowest percent initiating early prenatal care were non-Hispanic black (68 percent), Puerto Rican (67 percent), and American Indian mother (65 percent). Mothers who have problems getting prenatal care due to financial, scheduling, transportation, or other problems have lower rates of initiating early care. Mothers who wanted to be pregnant when they did were more inclined to initiate early care than mothers who did not want to become pregnant or whose pregnancies were mistimed. CONCLUSIONS: Prenatal care use in the United States did not improve in the 1980's but has been improving since 1990. Variations in use by demographic characteristics persist. There are wide gaps between mothers with easier access to prenatal care and those who encounter barriers to care. Mothers who want to become pregnant also tend to seek help in understanding their pregnancy and its risks earlier than those who did not intend to get pregnant or cared to become pregnant at another time.

Adolescent↗

Crystal structures of human calcineurin and the human FKBP12-FK506-calcineurin complex.

Calcineurin (CaN) is a calcium- and calmodulin-dependent protein serine/threonine phosphate which is critical for several important cellular processes, including T-cell activation. CaN is the target of the immunosuppressive drugs cyclosporin A and FK506, which inhibit CaN after forming complexes with cytoplasmic binding proteins (cyclophilin and FKBP12, respectively). We report here the crystal structures of full-length human CaN at 2.1 A resolution and of the complex of human CaN with FKBP12-FK506 at 3.5 A resolution. In the native CaN structure, an auto-inhibitory element binds at the Zn/Fe-containing active site. The metal-site geometry and active-site water structure suggest a catalytic mechanism involving nucleophilic attack on the substrate phosphate by a metal-activated water molecule. In the FKBP12-FK506-CaN complex, the auto-inhibitory element is displaced from the active site. The site of binding of FKBP12-FK506 appears to be shared by other non-competitive inhibitors of calcineurin, including a natural anchoring protein.

A Kinase Anchor Proteins↗

Right ventricular failure in patients requiring left ventricular assistance.

Right ventricular failure may complicate isolated left ventricular assistance. In a series of 8 patients undergoing left ventricular assistance in postcardiotomy cardiogenic shock, right ventricular failure developed in 5, directly contributing to death in all cases despite initially satisfactory support. Difficulty in grafting a dominant right coronary artery was a common factor in all cases. Early consideration should be given to biventricular support under these circumstances.

Aged↗

Hepatic portal venous flow in patients undergoing tricuspid valve surgery.

OBJECTIVE: To determine the changes of flow in the hepatic artery and portal vein of patients undergoing tricuspid valve repair together with mitral valve replacement. DESIGN: Non-randomised parallel group study. SETTING: Tertiary referral centre. PATIENTS: 18 patients with mitral valve disease with or without tricuspid regurgitation (age range 46-73; six men) and six patients with coronary artery disease and normal left ventricular function (women age range 39-78; four men). INTERVENTIONS: Mitral valve replacement with or without modified De Vega repair of the tricuspid valve or coronary artery bypass surgery. MAIN OUTCOME MEASURES: Flow in the hepatic artery and portal vein as measured by duplex Doppler flowmetry before and two to four weeks after operation. RESULTS: Preoperative hepatic artery flow was less in patients with mitral valve disease than in patients with coronary artery disease (162.7(13.1) ml.min-1 v 242.5(6.6) ml.min-1, p < 0.05). Portal vein perfusion was significantly reduced only in patients with associated tricuspid regurgitation compared with (844(83) ml.min-1 v 1422(64) ml.min-1 p < 0.05). Hepatic perfusion was unaltered after operation in patients undergoing coronary artery bypass surgery (p > 0.05). Flow in the hepatic artery and portal vein was improved only in patients undergoing mitral valve replacement with associated tricuspid valve repair (p < 0.05). CONCLUSION: Abnormalities of hepatic perfusion can be measured non-invasively in all patients with mitral valve disease but especially in those with associated tricuspid regurgitation needing valve repair. These abnormalities improved two to four weeks after mitral valve surgery and tricuspid valve repair, suggesting that measurement of portal flow might be a useful means of assessing the severity of tricuspid regurgitation.

Adult↗

Identification of vicinal thiols of phosphoenolpyruvate carboxykinase (GTP).

Phosphoenolpyruvate carboxykinase (PEPCK) from the cytosol of rat liver has 13 cysteines, at least one of which (Cys288) is known to be very reactive and critical for catalytic activity (Lewis, C. T., Seyer, J. M., and Carlson, G. M. (1989) J. Biol. Chem. 264, 27-33). Previous results provided evidence for the existence of at least 1 pair of vicinal cysteines within or near the active site of PEPCK (Lewis, C. T., Haley, B. E., and Carlson, G. M. (1989) Biochemistry 28, 9248-9255). An intramolecular cystine disulfide is induced to form upon treatment of PEPCK with equimolar 5,5'-dithiobis(2-nitrobenzoate) (Nbs2) or upon irradiation of the enzyme in the presence of the photoaffinity probe 8-azidoGTP. In each case, modification is accompanied by a substantial loss in catalytic activity, and substrates protect against inactivation and modification. We now report the identification of these modified thiols by differential alkylation of cysteines and half-cystines with radioactive iodoacetate, followed by isolation and sequencing of the modified tryptic peptides. The results indicate that the disulfide formed by equimolar Nbs2 lies within a 15-residue region of the PEPCK sequence that includes Cys399, Cys407, and Cys413. In addition, Cys407 and/or Cys413 also appear to participate in formation of the disulfide induced by 8-azidoGTP. These thiols lie very near a consensus sequence that has been suggested to represent the binding site for the guanine ring of GTP.

Alkylation↗

Effect of vascular clamp on endothelial integrity of the internal mammary artery.

The preservation of endothelial integrity is essential for maintaining patency of vascular grafts. The internal mammary artery flow is often interrupted with the application of a soft vascular clamp to achieve a bloodless field during the anastomosis. We investigated the effect of the vascular clamp on the internal mammary artery endothelium using the scanning electron and light microscope. The endothelium was examined before and at 15 and 30 minutes after clamping in both the pedicled and the skeletonized arteries. Endothelial integrity was breached by clamping with early evidence of platelet adhesion to the damaged areas. The severity of the endothelial damage was related to the clamp time, but there was no difference in the degree of damage between the pedicled and the skeletonized arteries. We conclude that the vascular clamp causes injury to the internal mammary artery endothelium and may be implicated in early postoperative graft failure.

Constriction↗

Surgical repair of aortic root aneurysms in 280 patients.

Bentall's technique for repair of annuloaortic ectasia has been associated with postoperative bleeding and with false aneurysms at the anastomotic site between the coronary orifices and valve-containing graft. To reduce the incidence of these complications, we modified the Bentall procedure, using a simplified technique to implant the graft and to create a fistula between the closed perigraft space and right atrium to control bleeding. A continuous suture of monofilament polypropylene was used to implant the prosthetic valve ring and to anastomose the coronary orifices to the Dacron fabric. In some instances, a brief period of hypothermic circulatory arrest was needed to perform the distal aortic anastomosis. Among 562 patients undergoing operation for aneurysm of the ascending aorta between January 1, 1980, and February 28, 1990, 280 underwent graft replacement with a valve-containing composite conduit. Most (82%) had annuloaortic ectasia. In 267, we performed a classic Bentall procedure with direct anastomosis between the coronary orifices and fabric graft. The remaining 13 patients underwent other procedures for coronary connection. Early mortality was 5.0%. Reoperation for bleeding was needed in 13.2% of patients who underwent operation before we used the right atrial fistula technique and in 4.4% after we began to use the technique (p = 0.044). Actuarial survival was 71% at 5 years and 65% at 7 years. For hospital survivors, it was 76% at 5 years and 70% at 7 years. During follow-up, only 9 patients have required reoperation. A false aneurysm at the coronary anastomosis, which was associated with prosthetic valve endocarditis, developed in 1 patient. No permanent fistulas have developed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Oesophageal erosion of an Angelchik prosthesis: surgical management using fundoplication.

Complications following insertion of the Angelchik prosthesis are becoming increasingly recognised. We report a 35-year-old patient with both mediastinal migration and intraluminal oesophageal erosion of a prosthesis. Successful management included transthoracic removal combined with a modified onlay fundoplication over the oesophageal defect to prevent gastro-oesophageal reflux.

Adult↗

Initial evaluation of an intracorporeal oxygenation device.

We describe a recently developed intracorporeal gas transfer device, its potential applications and hazards. To date, patients with potentially reversible respiratory failure have been treated with controlled oxygen therapy and positive pressure ventilation, but this treatment may itself contribute to lung parenchymal damage from barotrauma and oxygen toxicity. Total or partial extracorporeal gas exchange can be used to reduce these risks, but this treatment is complex and has significant morbidity and mortality. This gas exchange device has been designed to provide partial gas transfer with simplicity of insertion and use. The oxygenator lies in the vena cava to provide prepulmonary gas exchange. In preliminary studies with three calves we have shown that the device increases both mean mixed venous and arterial oxygen content and reduces mean arterial carbon dioxide tension.

Adult↗

Risk factors for cardiac operations in adult Jehovah's Witnesses.

During a 27-year-period, 663 adults of the Jehovah's Witness faith underwent open heart procedures at the Texas Heart Institute. To determine the effect of recent changes in operative techniques and in the patient population itself on early mortality, we reevaluated the surgical outcome in this special group of patients. We reviewed the charts of 88 consecutive Jehovah's Witness patients who had an open heart operation between January 1986 and March 1989 and compared demographic variables in this group with those of 575 patients who underwent operation between May 1963 and January 1986. In our recent series, patients were older (mean age, 61 years versus 54 years), and 16% were seen for repeat procedures. Early mortality (less than or equal to 30 days postoperatively) was lower in the recent series than in the earlier series (7.0% versus 10.7%), but the difference between the groups was not statistically significant. We identified several important factors associated with an increased risk of early death in the recent group of patients. These factors included repeat cardiac operations (p less than 0.01), especially for valvar dysfunction, severe left ventricular dysfunction (defined as an ejection fraction less than 0.35) (p less than 0.01), and a hemoglobin level lower than 80 g/L (8 g/dL) (p less than 0.01) on postoperative day 1. Although blood loss remains the leading cause of death in these patients, cardiac operations can be performed with an acceptable mortality.

Aged↗

Subcutaneous fat necrosis associated with pancreatic islet cell carcinoma.

A 75-year-old man with generalized subcutaneous fat necrosis was found to have an islet cell carcinoma of the pancreas. The histologic diagnosis of islet cell carcinoma was confirmed by electron microscopy, which showed characteristic intracytoplasmic granules. This is the second report of the association of islet cell carcinoma of the pancreas with generalized subcutaneous fat necrosis.

Adenoma, Islet Cell↗

Neo-intimal development on textured biomaterial surfaces during clinical use of an implantable left ventricular assist device.

Implantable left ventricular assist systems are being developed for long term clinical use. Prototype devices are currently used as extended mechanical bridges to cardiac transplantation. The Thermo Cardiosystems Inc. (TCI) pneumatic pusher plate left ventricular assist device (LVAD) features textured blood contacting surfaces to encourage the formation of an adherent fibrin-cellular coagulum. This serves as the foundation for the development of a neo-intimal lining. The TCI LVAD was implanted in 6 male patients (age range 22-53 years) between 1986 and 1988. The duration of implantation ranged from 1-41 days. No clinical thromboembolic events or pump-related thromboembolism occurred and none was evident at necropsy. The six device linings have been fully evaluated. Explanted devices were free of thrombus and calcification. Lining samples for light and electron microscopy were collected from areas of the diaphragm identical for flex and blood shear conditions and from high and low shear areas on the static housing. Islands of collagenous tissue were deposited on the static housing amongst compact fibrin. By day 13, cells populated the surface of the developing neo-intima overlying the diaphragm. By 41 days, the surface cell density increased and the cells became spindle shaped and relatively orientated in the high shear/flex area. Immunohistochemical techniques suggest that these cells are of mesenchymal origin. Textured blood contacting surfaces appear satisfactory in the preliminary clinical use of this device.

Adult↗

The use of an implantable left ventricular assist device following irreversible ventricular fibrillation secondary to massive myocardial infarction.

A TCI1 rough surface left ventricular assist device (LVAD) was implanted in a 47-year-old man who had sustained a recent massive myocardial infarction complicated by ventricular failure which remained unresponsive to intra-aortic balloon pump therapy and which was further complicated by irreversible ventricular fibrillation. Following implantation of the device and while awaiting a suitable donor organ for transplantation, further extension of the previous infarct resulted in left ventricular rupture and massive haemorrhage which led to his death. We report the successful use of the device in providing haemodynamic support, but caution against inordinate delay in bridging to transplantation patients who are at risk of extension of infarction.

Heart-Assist Devices↗