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Biomedical subjects

M S Bruno

Publications and source records attributed to M S Bruno.

At least 19 recordsLinked to original sources

LDL induced association of anionic liposomes with cells and delivery of contents as shown by the increase in potency of liposome dependent drugs.

PURPOSE: To establish whether anionic liposomes interact with the low-density lipoprotein (LDL) receptor, to determine the role of lipoproteins in this interaction, and whether the association causes functional delivery of encapsulated drugs. METHODS: The cell lines used were CV1-P and CHO wild type, both of which express the LDL receptor, and CHOldlA7, which lacks the LDL receptor. Cellular association of encapsulated methotrexate and fluorescein, labeled phosphatidylethanolamine in the lipid bilayer, was measured. Potency of three liposome dependent drugs (N-phosphonacetyl-L-aspartic acid, fluoroorotic acid, and methotrexate-gamma-aspartate) was also measured by growth inhibition. RESULTS: Association of liposomes containing at least 75 mol egg phosphatidylglycerol (ePG)/100 mol phospholipid with cells grown in defined medium supplemented with 1.0 mg/ml LDL was up to 30-fold higher with CV1-P or CHO wild type cells than with CHOldlA7, and 5-fold higher than association in defined medium lacking LDL. The addition of LDL did not yield any elevation of cellular association of distearoylphosphatidylglycerol liposomes. Increased association was paralleled by a corresponding increase in potency of all three liposome dependent drugs tested. CONCLUSIONS: ePG liposomes interact with the LDL receptor in an LDL-dependent fashion, and the interaction results in the delivery of contents to cells.

Animals↗

A novel series of amphiphilic imidazolinium compounds for in vitro and in vivo gene delivery.

We have developed three catioinic amphiphiles based on the structure 1-[2-(acyloxy)ethyl]-2-alkyl(alkenyl)-3-(2-hydroxyethyl)imidazolinium chloride. Although these three compounds differ only in the structure of the hydrophobic acyl chains, they differ greatly in their ability to mediate in vivo and in vitro gene delivery. Moreover, in vitro efficiency is not predictive of in vivo efficiency. The myristoyl form is the most effective compound in vitro, and the oleoyl form is the most effective compound in vivo. The compounds readily form suspensions in aqueous media, both in the pure form and as mixtures with either cholesterol or dioleoylphosphatidylethanolamine. These suspensions can be sonicated to produce smaller particles. Particle size, electron microscopy, and the ability to capture glucose suggest that these lipids form liposomes on suspension in aqueous media. When mixed with plasmid DNA, the lipid particles appear to fuse and form larger particles. Fusion is maximal at the critical DNA:lipid ratio where extensive aggregation and precipitation are observed. Therefore, these compounds behave similarly to other cationic liposome-forming lipids upon interaction with DNA.

Animals↗

GABAergic neurotransmission in the C57BL/10 sps/sps mouse mutant: a model of absence seizures.

The C57BL/10 sps/sps mouse mutant displays generalized absence seizure-like behavior. In these mice, glutamic acid decarboxylase activity is reduced in the cortex and hippocampus. Tritiated flunitrazepam binding (3H-flu) is reduced in these areas, as well as in midbrain, cerebellum, and pons-medulla. Quantitative [3H]-flunitrazepam binding autoradiography confirms these observations. GABA uptake by synaptosomes from sps/sps mice is also reduced in all the areas studied. Potassium-stimulated, Ca(2+)-dependent release of radioactivity from synaptosomes preloaded with [14C]-GABA is reduced in the hippocampus, increased in midbrain and pons-medulla, but remains unaltered in the cortex. These results suggest region-specific alterations in GABAergic neurotransmission that may be responsible for the absence-like seizures in C57BL/10 sps/sps mice.

Animals↗

High-affinity binding of proline to mouse brain synaptic membranes.

There is evidence suggestive of the possible neuromodulatory role for L-proline in the mammalian brain. The binding of proline to whole mouse brain synaptic membranes has been partially characterized. Several binding sites for this imino acid have been identified; one in the nanomolar range and at least two in the submicromolar range. The binding of proline is inhibited by NaCl. Pipecolic acid (40 microM), ornithine, aminooxyacetic acid (AOAA), glycine, GABA, and glutamate were capable of significantly inhibiting proline binding. Although detailed pharmacological and functional studies are needed, these results are consistent with a brain-specific function for this imino acid, as well as, with the presence of specific binding site(s) for proline.

Amino Acid Transport Systems, Neutral↗

Proline binding to mouse brain synaptosomes.

L-proline has been shown to exert a variety of physiological and behavioral effects that are consistent with its possible role as a neuromodulator in the mammalian brain. The binding of l-proline to mouse brain synaptosomes has been partially characterized. Preliminary kinetic analysis shows the presence of at least two binding sites in the submicromolar range, and one in the nanomolar range. While more detailed studies are necessary as to determine the biological significance of proline binding to mouse brain synaptosomes, these results further support the possible role of proline as a neuromodulator.

Amino Acid Transport Systems, Neutral↗

Current status of intra-aortic balloon counterpulsation in critical care cardiology.

Retrospective analysis revealed that intra-aortic balloon counterpulsation was attempted in 321 patients at our institute from August 1, 1974, to July 1, 1982. The intra-aortic balloon pump (IABP) was successfully inserted in 298 cases (93%). Indications for an IABP included: cardiogenic shock (84 cases), preoperative hemodynamic coverage (15 cases), low-output syndrome (73 cases), pre- and postinfarction angina (75 cases), intractable congestive heart failure (12 cases), refractory ventricular arrhythmia (9 cases), percutaneous transluminal coronary angioplasty (14 cases), cardiac arrest (7 cases), and a miscellaneous group (9 cases). The overall major complication rate was 9%. The data from this experience support aggressive management of cardiogenic shock, i.e., early balloon insertion, angiography, and cardiac surgery, which significantly increases the survival rate (83%) over medical therapy combined with balloon counterpulsation alone. The IABP was also extremely effective in managing other high-risk categories when combined with some form of definitive mechanical correction, e.g., coronary revascularization, valve replacement, or percutaneous transluminal coronary angioplasty. Left ventricular (LV) function was a significant indicator of long-term survival in our series. Patients with normal or moderately impaired LV function had higher survival rates (95% and 82%, respectively) than patients with poor LV function (42%).

Adolescent↗

Renal disease in patients with AIDS: a clinicopathologic study.

To determine the nature and frequency of renal disorders in AIDS we reviewed the records of thirty-two patients hospitalized over a twenty-two month period. Group I, including all patients with AIDS who demonstrated proteinuria and/or renal insufficiency, numbered thirteen patients, in ten of whom renal tissue was available. Renal abnormalities included proteinuria in twelve patients, which exceeded two grams per day in seven. The glomerular histologic lesions included focal glomerulosclerosis, diffuse mesangial hypercellularity, diffuse proliferative glomerulonephritis, and membranoproliferative glomerulonephritis. The nonglomerular histologic lesions included acute tubular necrosis, nephrocalcinosis, focal interstitial nephritis, and one case each of intrarenal cryptococcal infection and renal cell carcinoma. Nine of these thirteen patients developed renal insufficiency, and four of them required dialysis. Their mortality by the end of the study period was eleven of thirteen patients (85 percent), significantly worse in the short term than AIDS patients without renal problems. The patients in Group I were compared to the nineteen AIDS patients without renal abnormalities in Group II. The Group I patients had a higher incidence of oral and esophageal candidiasis, other fungal infections, and infections with Mycobacterium avium-intracellulare. They also had a higher incidence of exposure to aminoglycoside antibiotics and amphotericin B, and experienced more clinical shock than their Group II counterparts. It is concluded that patients with AIDS may demonstrate renal abnormalities on the basis of immune, hemodynamic, infectious, and neoplastic derangements.

Acquired Immunodeficiency Syndrome↗

The role of intra-aortic balloon counterpulsation in patients undergoing percutaneous transluminal coronary angioplasty.

Between June, 1979, and July, 1982, 14 patients required an IABP in conjunction with PTCA. The clinical indications for balloon counterpulsation, in the performance of PTCA were (1) clinically unstable situations where PTCA might otherwise be contraindicated, e.g., left main stem disease, multivessel coronary artery disease, unstable anginal syndromes, and cardiogenic shock; (2) preoperative insertion of an IABP for added safety following unsuccessful angioplasty; (3) abrupt vessel closure during a PTCA procedure in which the patient becomes hemodynamically unstable; and (4) late vessel closure following an initially successful angioplasty resulting in hemodynamic compromise. Of the 14 cases requiring balloon counterpulsation, 13 survived hospitalization and were alive at the time this report was submitted. We conclude that IABP is a useful adjunct to PTCA in a variety of clinical circumstances.

Adult↗

Comparison of wire-guided percutaneous insertion and conventional surgical insertion of intra-aortic balloon pumps in 151 patients.

Over a 25-month period, percutaneous wire-guided balloon catheter insertion was attempted in 51 patients, and intra-aortic balloon pump insertion was attempted by conventional surgical method in 100 patients. The success rate in the group undergoing percutaneous insertion was 90.2 percent (46 of 51) and 90 percent in the group undergoing surgical insertion (90 of 100). The indications for intra-aortic balloon counterpulsation were diverse in both groups. The major complication rate in the patient population undergoing percutaneous intra-aortic balloon pump insertion was 15.2 versus 15.6 percent for the surgical group, and there were no cases of leg amputation or aortic dissection in the percutaneous group; however, two cases of leg amputation and one case of aortic dissection resulting in death occurred in the surgical group. The percutaneous intra-aortic balloon pump insertion technique was successfully employed in conjunction with percutaneous transluminal coronary angioplasty in six cases. It is concluded that the wire-guided percutaneous balloon catheter method is a highly successful and rapid means of instituting intra-aortic balloon counterpulsation in a wide variety of clinical situations. However, because of the significant associated complication rate, the decision to institute balloon counterpulsation must weigh the benefit-to-risk ratio, and this procedure must still be evaluated on a case-by-case basis.

Adult↗

Management of acute cardiac tamponade by subxiphoid pericardiotomy.

Eighteen patients with cardiac tamponade were treated by subxiphoid pericardiotomy performed with the patients under local anesthesia. This group included 9 cases of uremic pericarditis (50%), 5 cases of metastatic cancer (28%), 2 cases of trauma (11%), 1 case of tuberculosis (5.5%), and 1 case of unknown cause. Immediate relief from acute cardiac tamponade was obtained in all 18 cases with only minor and self-limiting postoperative complications, including transient supraventricular arrhythmias (five cases) and fever (five cases). There were no deaths related to either the operative procedure or reaccumulation of the pericardial effusion. The drainage period averaged 9.6 days (range, three to 28 days). Pericardial biopsy was performed in 15 of 18 cases. We conclude that subxiphoid pericardiotomy is a safe and effective method for the management of pericardial effusion of diverse causes. The ability to perform this technique safely using local anesthesia and the capacity to obtain a biopsy specimen under direct visualization make this technique superior to both needle pericardiocentesis and pericardiectomy in the acutely ill patient.

Acute Disease↗

The brachial artery method to transluminal coronary angioplasty.

The development of a brachial artery guiding catheter for (percutaneous) transluminal coronary angioplasty is described. Three-hundred angioplasty procedures were attempted with 196 (65%) via the branchial and 104 (35%) via the femoral artery. The coronary stenosis was crossed in 202 attempts (67%); in 138 via the brachial (70%) and 64 via the femoral artery (62%). A successful angioplasty occurred in 117 via the brachial (85%) and in 50 via the femoral artery (78%). Successful angioplasty of the left anterior descending artery was equally effective with either technique. Successful angioplasty of the right coronary artery was more difficult (P less than 0.05) using the femoral artery. An unsuccessful angioplasty with one technique was occasionally overcome by use of the other technique. No brachial artery complications were encountered. The brachial method to transluminal coronary angioplasty is an acceptable and complementary alternative to the femoral technique. Those laboratories contemplating percutaneous transluminal coronary angioplasty may desire to utilize both approaches.

Angina Pectoris↗

Laser coronary angioplasty: experience with 9 cadaver hearts.

Experience with laser angioplasty in 16 coronary arteries in 9 cadaver hearts is presented. Coronary obstructions were due to experimentally created thrombi as well as to naturally occurring calcified plaques. Successful laser angioplasty was achieved in 14 of 15 arteries. One artery was sacrificed to determine factors necessary for deliberate perforation of the arterial wall. This procedure required more than 30 seconds of laser energy at 3.0 W with the catheter tip almost perpendicular to the wall. Penetration of the arterial wall occurred only in the second left anterior descending artery which was plaque-occluded because of operator inexperience.

Angioplasty, Balloon↗