PubMed Health⌕ Search

Biomedical subjects

J E Molina

Publications and source records attributed to J E Molina.

At least 19 recordsLinked to original sources
PubMed2006

Intrinsic FAK activity and Y925 phosphorylation facilitate an angiogenic switch in tumors.

Elevated focal adhesion kinase (FAK) expression occurs in advanced cancers, yet a signaling role for FAK in tumor progression remains undefined. Here, we suppressed FAK activity in 4T1 breast carcinoma cells resulting in reduced FAK Y925 phosphorylation, Grb2 adaptor protein binding to FAK, and signaling to mitogen-activated protein (MAP) kinase (MAPK). Loss of a FAK-Grb2-MAPK linkage did not affect 4T1 cell proliferation or survival in culture, yet FAK inhibition reduced vascular endothelial growth factor (VEGF) expression and resulted in small avascular tumors in mice. This FAK-Grb2-MAPK linkage was essential in promoting angiogenesis as reconstitution experiments using Src-transformed FAK-null fibroblasts revealed that point mutations affecting FAK catalytic activity (R454) or Y925 phosphorylation (F925) disrupted the ability of FAK to promote MAPK- and VEGF-associated tumor growth. Notably, in both FAK-inhibited 4T1 and Src-transformed FAK-null cells, constitutively activated (CA) mitogen-activated protein kinase kinase 1 (MEK1) restored VEGF production and CA-MEK1 or added VEGF rescued tumor growth and angiogenesis. These studies provide the first biological support for Y925 FAK phosphorylation and define a novel role for FAK activity in promoting a MAPK-associated angiogenic switch during tumor progression.

Animals↗
PubMed2000

Approach to the confluence of the subclavian and internal jugular veins without claviculectomy.

A new technique is described to approach the confluence of the subclavian vein and the internal jugular, as well as to expose the innominate vein from its origin to the superior vena cava. The operation accomplishes decompression of the subclavian vein and allows direct approach of the subclavian and the innominate veins. It avoids dividing the clavicle or disarticulating the sternal-clavicular joint. It also has the advantage of accomplishing the procedure without entering the pleural cavity. Its reconstruction is explained in detail and achieves solid stability of the sternum and of the shoulder girdle. This approach also prevents deformity that other operations proposed in the past may cause.

Clavicle↗
PubMed1998

A new surgical approach to the innominate and subclavian vein.

A new technique extending the incision used for thoracic outlet decompression with a subclavicular approach to the first rib is presented. After the first rib and scalenotomy are removed, the subclavicular incision is continued into the sternum medially and superiorly to the sternal notch. This gives easy access to the innominate-subclavian-axillary vein segment. Eight patients with extensive chronic fibrotic obstruction of the subclavian-innominate vein segment underwent operation with this technique. It allows placement of either long patches of saphenous vein to reestablish normal caliber or replacement, as is our choice, with a small-sized cryopreserved descending thoracic aortic homograft. The operation is carried out in an extrapleural plane preserving the sternoclavicular joint, avoiding the deformity caused by transclavicular techniques. Repair of the sternotomy creates a stable incision. Follow-up to 14 months shows patency of the venous channel with no complications. This surgical approach is recommended to solve the problem of satisfactory exposure of the subclavian-innominate venous channel after decompression of the thoracic outlet.

Adolescent↗
PubMed1998

Combined posterior and transaxillary approach for neurogenic thoracic outlet syndrome.

BACKGROUND: Incomplete removal of the first rib in operations intended to decompress the thoracic outlet is often seen after the single transaxillary approach (often leaving a posterior stump) or supraclavicular techniques (leaving an anterior stump). The former may also cause neurogenic and vascular injuries because the exposure is often poor in attempting complete removal of the first rib posteriorly and the surgeon faces a significant struggle. STUDY DESIGN: A new operative procedure is described entailing two stages using two separate incisions: a transaxillary and posterior incision done at the same sitting that accomplishes complete removal of the first rib with less risk. This combined approach is done with the help of a new arm holder device during the transaxillary stage followed by a small incision behind the trapezius ridge for posterior access to the rib. RESULTS: I present 33 patients in whom this operation was implemented, with a cure rate of 79%, improvement in 15%, and unchanged in 6%, with no complications or mortality. Technical details are presented. CONCLUSIONS: A double-incision approach is recommended as a safer and more effective method to accomplish complete removal of the first rib than are single transaxillary supraclavicular techniques in cases with thoracic outlet obstruction.

Adolescent↗
PubMed1997

Undertreatment and overtreatment of patients with infected antiarrhythmic implantable devices.

BACKGROUND: Infection of implantable defibrillators or pacemakers is a serious complication, reported with increasing frequency probably because of an increase in the total number of devices implanted due to a change in trends in the treatment of arrhythmias. This review is aimed to provide guidelines on how to deal with these infections and which method is most likely to be successful. METHODS: This is a review of 38 patients with infected antiarrhythmic implantable devices under three different plans of therapy. There were 17 implantable cardioverter defibrillators and 21 pacemakers. In 27, infection occurred after primary implantation (15 pacers, 12 implantable cardioverter defibrillators), and in 11 after replacement (six pacers, five implantable cardioverter defibrillators). Three therapeutic plans were identified. Group I (n = 12) received intravenous antibiotics without removal of the antiarrhythmic implantable device, but with relocation to a different area or plane, and with or without the use of a topical irrigating-suction system. Group II (n = 19) had complete removal of the system, 2 weeks of intravenous antibiotics, and implantation of a new unit followed by 10 more days of antibiotics. Group III (n = 7) underwent complete removal, 6 weeks of antibiotics, implantation of a new unit, and another 6 or more weeks of antibiotic therapy. RESULTS: Failure occurred in 100% of cases in group I. Groups II and III had complete clearing of infection and successful reimplantation of new systems with no recurring infections. Follow-up was 8 months to 5 years. Two deaths occurred, both in group I. Hospitalization for groups I and III was 104 days and 65 days, respectively, versus 22 days for group II. No deaths occurred in group II or III. CONCLUSIONS: With an infected antiarrhythmic implantable device, immediate removal of the entire unit is recommended, followed by 2 weeks of intravenous antibiotics, implantation of a new system, and 10 more days of postoperative antibiotics. This regimen is sufficient to cure the problem. No attempts should be made to save an infected system from removal because it endangers the patient's life, prolongs hospitalization, increases costs, and most likely will fail.

Adolescent↗
PubMed1996

Perforation of the right ventricle by transvenous defibrillator leads: prevention and treatment.

A series of 78 consecutive implants of the transvene PCD (Medtronic, Inc.) defibrillator system is presented and the occurrence of right ventricular perforation in 4 patients reported (5.2%). Diagnosis of perforation is made using four signs: (1) decrease in arterial blood pressure without any other explanation; (2) decrease in pulsatility of the cardiac silhouette as monitored by fluoroscopy; (3) increased size of the cardiac silhouette; and (4) abnormal position of the transvenous lead too far out toward the left ventricle along the pericardial outline. Perforation causes rapid and dramatic cardiac tamponade due to the large diameter and stiffness of the coil carrier lead. Immediate drainage of the hemopericardium must be carried out using the transxiphoid approach. The use of a thin blue-coded lead stylet (0.014-inch gauge) is recommended over the stiffer maroon-coded stylet. Since treatment must be carried out immediately, it is advised that a surgeon either perform, assist, or be immediately available whenever one of these systems is implanted.

Adult↗
PubMed1995

Implantation of transvenous pacemakers in infants and small children.

A series of 14 infants and small children ranging from 7 months to 7 years in age (mean, 2.5 years) underwent implantation of transvenous pacemaker systems. Three factors are of utmost importance in children: small subclavian vein size, thin subcutaneous layer in the chest, and growth. A five-point protocol is followed strictly: (1) duplex assessment of upper veins, (2) use of active fixation leads, (3) use of short (36 to 45 cm) leads, (4) anchoring of pulse generator with nonabsorbable material to prevent migration, and (5) routine use of the "lateral approach" in children more than 2 years old when the pulse generator is implanted in the chest. Because lead diameters measure 2 to 2.3 mm, a one-lead system needs a vein diameter of 5 mm (cross-sectional area of 19 mm2). A two-lead system needs a vein at least 7 mm in diameter and a cross-sectional area of 38 mm2 to prevent vein occlusion. Therefore all children less than 3 years of age had the leads implanted via the internal jugular vein. In 50% of children between 4 and 7 years of age, the internal jugular system also was used. Children more than 7 years old have leads implanted via the subclavian veins. Duplex ultrasound assessment of the upper veins is important to decide route of implantation. Use of short leads is recommended to reduce bulk at the pulse generator site. The "lateral approach" prevents problems at the generator implantation site.

Adolescent↗
PubMed1995

Crinkling of epicardial defibrillator patches. A common and serious problem.

The durability and reliability of the implantable cardioverter-defibrillator epicardial patch systems have not been reported. In 128 consecutive patients such systems manufactured by Cardiac Pacemakers, Inc. (St. Paul, Minn.) or Medtronic, Inc. (Minneapolis, Minn.) were implanted with 100% follow-up to investigate the rate of patch crinkling and its consequences. A total of 122 patients survived the operation (operative mortality, 6 patients: 4.7%). Ninety-four patients received Cardiac Pacemakers, Inc. AICD patches and 28 received Medtronic PCD patches. Patients had chest x-ray studies every 3 to 6 months and function of the defibrillator was checked every 3 months. Late mortality occurred in 17 patients (13%) leaving a total of 105 long-term survivors (82%) to the present. Among 122 survivors, severe crinkling of the patches occurred in 48 patients--33 in the Cardiac Pacemakers, Inc. AICD group (36%) and 15 in the PCD group (54%)--within 2 years of the implant. Crinkling of patches caused not only malfunction of the system, but also cardiac pain in three patients. Crinkling occurred as early as 2 months after implant and progressed throughout the period of observation. Fourteen patients later required implant of an additional transvenous defibrillator because of failure of the epicardial system. The percentage of transvenous implantable cardioverter-defibrillator systems needed was higher for the Medtronic group (28%) than for the Cardiac Pacemakers, Inc. AICD group (6.3%). Both systems have shown an unacceptably high rate of patch crinkling that occurs in a relatively short time. There is no difference whether a thoracotomy or midline sternotomy is used or whether the patches are implanted intrapericardially or extrapericardially. The quest should continue for a better patch system design.

Adult↗
PubMed1995

Composite and plain tubular synthetic graft conduits in right ventricle-pulmonary artery position: fate in growing lambs.

Our goal was to identify the most appropriate material for right ventricle-pulmonary artery conduits in growing animals. We used 100 lambs that were 3 to 4 weeks old (mean weight 11.7 kg). Follow-up was up to 24 months. Group I received plain tubular conduits: (1) Dacron knitted fabric, (2) collagen-coated knitted fabric, (3) Milliknit and Microknit material, (4) woven Dacron fabric, (5) three-dimensional Dacron fabric (crossweave 500 and 800), or (6) polytetrafluoroethylene. Group II received either a (1) woven Dacron fabric conduit with a built-in tissue valve or (2) polytetrafluoroethylene graft with a built-in St. Jude Medical valve. We did angiograms and catheterizations every 3 to 6 months and killed the lambs at 6, 12, 18, or 24 months. Tubular Dacron fabric woven or knitted grafts, regardless of matrix, pore size, thickness, or coating, caused formation of a thick acellular pseudointima buildup, which led to progressive obstruction starting as early as 3 months. Polytetrafluoroethylene grafts in groups I and II showed the formation of thin inner and outer capsules (0.5 mm) and none developed obstruction despite wall calcification. Conduits of woven Dacron fabric with a built-in tissue valve degenerated rapidly, leading to calcification thrombosis and obstruction within 3 months; no lamb survived 12 months. Polytetrafluoroethylene conduits with a St. Jude Medical valve in lambs receiving anticoagulants remained free of obstruction and continued to function well. It appears that synthetic conduits of polytetrafluoroethylene perform well in either of the situations here tested and may be the best choice at present.

Animals↗
PubMed1995

Need for emergency treatment in subclavian vein effort thrombosis.

BACKGROUND: Effort thrombosis of the subclavian vein is often inadequately treated--and most of the time treatment is late. Physicians are unfamiliar with this syndrome and its treatment. STUDY DESIGN: In 65 patients with this syndrome, three major categories were recognized. The acute group (less than one week) comprised 14 patients subdivided into first time occurrence, recurrent episode, or occurrence after previous surgery for thoracic outlet. The subacute group (between one and two weeks) comprised four patients with the same subdivisions as the acute group. The chronic group (greater than two weeks) comprised 47 patients. Acute and subacute cases were treated with direct lytic therapy (urokinase) followed by operation. An anterior subclavicular approach was used to remove the first rib, subclavius, and anterior scalene muscles and to have safe access to the vein. Patients in the chronic stage required vein patch angioplasty of the strictured segment. RESULTS: In acute cases (first time occurrence) decompression of the vein only at the thoracic outlet was effective in 100 percent of cases (eight patients). Vein patch angioplasty was needed in recurrent, subacute, and chronic cases. This procedure was 100 percent effective if stenosis was less than 2 cm long. Longer-segment obstructions had only a 37.5 percent (three of eight) success rate. Fourteen patients were considered inoperable. CONCLUSIONS: It is recommended that effort thrombosis of the subclavian vein be treated acutely with thrombolytic agents followed by operation. This aims to prevent chronic fibrous obliteration of the subclavian vein, which is a consistent complication in patients who have had delayed treatment for more than two weeks. If operable, chronic stage patients always require vein patch angioplasty.

Acute Disease↗
PubMed1993

Primary closure for infected dehiscence of the sternum.

I propose a new irrigation-suction system to achieve primary closure of the sternum in cases of postoperative infected dehisced sternotomy. Of 16 cases, I had no treatment failures, no recurring infections, and no patient deaths after 1 to 8 years of follow-up. The new system entails retrosternal and superficial sets of tubes, both in double-staggered position, with primary closure of the sternum and of the skin. Skin or muscle flaps are avoided, and the stability of the chest cage is maintained. Hospitalization time is 14 to 18 days.

Adolescent↗