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Biomedical subjects

S Ramamurthy

Publications and source records attributed to S Ramamurthy.

At least 19 recordsLinked to original sources

Sulfatides: targets for anti-phospholipid antibodies.

BACKGROUND: Sulfatides are sulfated glycosphingolipids expressed on the surface of erythrocytes, leukocytes, and platelets. Sulfatides interact with several cell adhesion molecules involved in hemostasis. Beta2-glycoprotein I is an anionic phospholipid-binding plasma protein, and the phospholipid-bound form is the target for most anti-phospholipid antibodies that are associated with recurrent thrombosis, miscarriages, and neurological symptoms. In this study, we examined whether beta2-glycoprotein I forms a complex with sulfatides and thereby becomes a target for anti-phospholipid antibodies. METHODS AND RESULTS: Beta2-glycoprotein I binds to surface-bound sulfatides but not to other glycolipids, such as ceramide, cerebrosides, sphingomyelin, or ganglioside. At a sulfatide coating density of 1 microg/well, beta2-glycoprotein I reaches half-maximal binding at 2.5 microg/mL, and the binding is saturated at 10 microg/mL. The binding of beta2-glycoprotein I also depends on the coating density of sulfatides in the well. At a constant beta2-glycoprotein I concentration of 5 microg/mL, maximal binding of beta2-glycoprotein I is observed at a coating density of 1 mug/well. The serum from 14 patients with anti-cardiolipin antibodies, a subset of anti-phospholipid antibodies, bound to sulfatide-bound beta2-glycoprotein I and previous absorption on cardiolipin-coated surfaces decreased the immunoreactivity toward sulfatide-beta2-glycoprotein I complex by >50% in 12 of 14 patients. Furthermore, immunoaffinity-purified anti-cardiolipin antibodies from 4 of 5 patients reacted with sulfatide-bound beta2-glycoprotein I. CONCLUSIONS: These results show that not only anionic phospholipids, as commonly known, but also sulfatides are targets for most anti-phospholipid antibodies. We therefore postulate that interactions of these antibodies with sulfatides may contribute to some of the clinical symptoms of the anti-phospholipid antibody syndrome.

Antibodies, Anticardiolipin↗

Risk factors for recurrence of atrial fibrillation in patients undergoing hybrid therapy for antiarrhythmic drug-induced atrial flutter.

AIMS: Catheter ablation of the inferior vena cava-tricuspid annulus isthmus and continuation of antiarrhythmic drug therapy have been shown to be an effective hybrid therapy for atrial flutter which results from antiarrhythmic drug treatment of atrial fibrillation. The aim of this study was to determine the risk factors for recurrence of atrial fibrillation in patients undergoing hybrid therapy for antiarrhythmic drug-induced atrial flutter. METHODS AND RESULTS: 90 patients with paroxysmal (n=46) or persistent atrial fibrillation (n=44) developed atrial flutter due to the administration of amiodarone (n=48), flecainide (n=22), propafenone (n=14) or sotalol (n=6). Recurrence of atrial fibrillation after ablation was assessed during follow-up on continued antiarrhythmic drug therapy and during long-term follow-up, irrespective of the initial antiarrhythmic medication. During the follow-up on continued antiarrhythmic drug therapy (16+/-13 months), recurrence of atrial fibrillation was documented in 24 of 90 patients (27%). The presence of accompanying pre-ablation episodes of atrial fibrillation on antiarrhythmic treatment (Odds ratio 7.1, 95% confidence interval 2.3 to 25, p=0.001) and decreased left ventricular ejection fraction (Odds ratio 3.7, 95% confidence interval 1.01 to 12.5, p=0.048) were significant and independent predictors of post-ablation atrial fibrillation. Antiarrhythmic medication was discontinued during long-term follow-up due to adverse drug effects (amiodarone, n=12; flecainide, n=1) in 13 patients (14%). During the long-term follow-up, irrespective of the initial antiarrhythmic medication (21+/-15 months), stable sinus rhythm was maintained in 60 of 90 patients (67%). CONCLUSION Hybrid therapy can be considered as the first line therapy for patients with antiarrhythmic drug-induced atrial flutter but patients should be carefully evaluated for accompanying pre-ablation episodes of atrial fibrillation and possible adverse drug effects before initiation of hybrid therapy.

Analysis of Variance↗

Extensive dissection requiring multiple stents following balloon angioplasty for non-specific aorto-arteritis.

Discrete stenoses of the thoraco-abdominal aorta in non-specific aorto-arteritis are considered favorable lesions for balloon angioplasty characterized by good results without major complications. Herein, we describe one such case manifesting with severe hypertension, left ventricular dysfunction and congestive heart failure treated by angioplasty. Balloon dilatation, however, resulted in extensive dissection requiring implantation of two Wallstents. Over a follow-up of one year, hypertension remained under good control with fewer drugs and symptom relief was maintained. Left ventricular ejection fraction improved from 35% to 61%.

Adolescent↗

Successful inoue balloon valvotomy in a difficult case of mitral stenosis using multiple modifications of technique: alternative method for loop formation of the Inoue balloon catheter.

Transseptal puncture was accomplished with difficulty at an unfavorable site in a case of severe mitral stenosis with distorted atrial and septal anatomy. Septal balloon entrapment could not be avoided during attempts to cross the mitral valve using the standard technique. This problem was circumvented by resorting to the loop method and the left ventricle was entered first with a guidewire, which then supported the balloon catheter. Successful mitral valve dilatation could thus be performed. A simple alternative method that was used to form the Inoue balloon catheter into a loop is also described.

Adult↗

Reduced rearing temperature augments responses in sympathetic outflow to brown adipose tissue.

Sympathetic outflow to brown adipose tissue (BAT) contributes to both thermoregulation and energy expenditure in rats through regulation of BAT thermogenesis. Acute cold exposure in mature animals augments BAT thermogenesis; however, the enhanced BAT thermogenic response returns to normal shortly after cessation of the cold exposure. In this study, we sought to determine whether cold exposure in early neonatal life could induce enhanced responses in the sympathetic outflow to BAT and whether this altered sympathetic regulation would be sustained after the cold stimulus was removed. BAT sympathetic nerve activity (SNA) was recorded in urethane-chloralose-anesthetized, artificially ventilated rats that were raised from birth in either 18 or 30 degrees C environments and then, at 8 weeks of age, were maintained in 23 degrees C for at least 4 weeks. An acute hypothermic stimulus, disinhibition of a brainstem thermogenic network in the raphe pallidus, or electrical stimulation in this raphe site produced increases in BAT SNA that were twice as great in rats reared at 18 degrees C as in those reared at 30 degrees C. The norepinephrine content of the interscapular BAT (IBAT) and the number of sympathetic ganglion cells projecting to interscapular BAT were 70% greater in the 18 degrees C-reared rats. We conclude that neonatal exposure to a cold environment induces a permanent developmental alteration in the capacity for sympathetic stimulation of BAT thermogenesis that may be mediated, in part, by a greater number of sympathetic ganglion cells innervating BAT in cold-reared animals.

Acclimatization↗

Utility of coaxial technique for renal angioplasty in patients with a difficult-to-cross stenosis.

The aim of this study was to evaluate the feasibility of coaxial approach in difficult-to-cross lesions in patients with failed percutaneous transluminal renal angioplasty by conventional over-the-wire exchange technique. Twelve stenoses in 10 patients (six women and four men; age range 19 +/- 7 years) with uncontrolled hypertension were treated by this method. The stenosis was caused by nonspecific aortoarteritis in 8 patients and fibromuscular dysplasia in 2 patients. It was ostial in seven and post-ostial in five vessels. Conventional exchange technique was unsuccessful in all of them. All procedures were done by femoral route. Technical success was seen in 11 (92%), without complication. The stenosis improved from 90 +/- 2.1% (range 80-100%) to 6 +/- 7% (range 0-20%), blood pressure decreased from 198 +/- 12.3 mm Hg (range 180-220 mm Hg)/130 +/- 6.7 mm Hg (range 120-140 mm Hg) to 119 +/- 5.7 mm Hg (range 110-130 mm Hg)/83 +/- 3.9 mm Hg (range 80-90 mm Hg), and number of drug treatments for hypertension fell from 3.6 +/- 0.52 (range 3-4) to 1 +/- 0.94 (range 0-3; p < 0.01). Percutaneous transluminal renal angioplasty resulted in "cure" in 3 patients and "improvement" in 7 patients. Follow-up period was 3-21 months (mean 6.4 months). No restenosis was detected. Coaxial approach is safe and effective in treating difficult-to-cross lesions in which renal angioplasty by conventional exchange technique is unsuccessful.

Adult↗

Isolated congenital anterior mitral leaflet cleft: a rare cause of mitral insufficiency.

BACKGROUND AND AIM OF THE STUDY: Isolated cleft of the anterior mitral leaflet is a rare cause of mitral insufficiency. Although an established entity, due to its rarity the exact anatomic diagnosis is difficult to establish unless sought specifically. METHODS: Four patients (age range: 16 to 26 years) with isolated cleft of the anterior mitral leaflet were treated at the authors' institute. Clinical symptoms were typical of mitral insufficiency; the exact anatomic diagnosis was not established preoperatively in any patient. The cleft was directly sutured in all four patients and additional annuloplasty was performed in three. RESULTS: Postoperative echocardiography confirmed satisfactory results. After a mean follow up of 46.7 months (range: 3 to 84 months), one patient had mild mitral insufficiency and the remaining patients had no mitral regurgitation. CONCLUSION: In severe mitral insufficiency with no obvious mitral valve pathology and an intact atrial septum, a cleft of the anterior mitral leaflet should be sought. Repair of the cleft can restore normal mitral valve function.

Adolescent↗

Coarctation of Aorta Mimicking Aortic Arch Interruption and its Successful Dilatation by an Innovative Approach.

Balloon dilatation for coarctation of the aorta is an established alternative to surgery in older children and young adults with a high success rate and a low incidence of restenosis.1Ð4 However, balloon dilatation has to be performed with extreme caution when the coarct segment involves the major branches of the aortic arch or when the coarct has an atypical anatomy. Herein, we report an unusual case which was suggestive of aortic arch interruption on descending thoracic aortography and could not be crossed retrogradely. Brachial approach for ascending aortography revealed that this was indeed a coarct with a distorted anatomy and also made possible crossing of the coarct antegradely. After exteriorizing the guide wire across the coarct with the help of a snare device advanced through the femoral arterial sheath, the coarct could be dilated from the femoral route as is routinely done.

Journal Article↗

Effect of pre-treatment with transdermal glyceryl trinitrate on myocardial ischaemia during coronary angioplasty.

OBJECTIVE: In the light of the reported inconsistent anti-ischaemic and antianginal effects of transdermal glyceryl trinitrate, its efficacy and influence on the effects of intracoronary glyceryl trinitrate were examined during coronary angioplasty, which provides a model of controlled, reversible ischaemia. DESIGN: Double blind, randomised study of the effect of transdermal and intracoronary glyceryl trinitrate on ischaemia during coronary angioplasty. PATIENTS: 40 patients with isolated severe stenosis of the left anterior descending coronary artery. INTERVENTIONS: Patients were randomised (double blind) to transdermal glyceryl trinitrate (10 mg per day) and placebo, starting four to six hours before angioplasty. After 4 one-minute balloon inflations intracoronary glyceryl trinitrate was injected (0.2 mg) and then 4 further one-minute inflations were performed. MAIN OUTCOME MEASURES: The time to angina and the time to > 0.2 mV ST shift on surface electrocardiogram (ECG) or intracoronary ECG during the individual inflations. RESULTS: These times did not significantly differ during initial inflations between transdermal glyceryl trinitrate (27 (11), 25 (9), and 19 (9) s, respectively) and placebo (34 (11), 30 (8), and 21 (7) s. After intracoronary glyceryl trinitrate, they were significantly prolonged compared with the initial values, without differences between patients with transdermal glyceryl trinitrate (37 (10), 30 (8), and 23 (8) s, respectively) or placebo (39 (15), 36 (11), and 28 (12) s). Ischaemic preconditioning was not seen. CONCLUSIONS: Transdermal glyceryl trinitrate (10 mg per day), unlike intracoronary glyceryl trinitrate, did not alleviate the myocardial ischaemia produced by balloon inflation during coronary angioplasty.

Administration, Cutaneous↗

Matrix metalloproteinases and their inhibition in periodontal treatment.

Matrix metalloproteinases (MMPs), produced by both infiltrating and resident cells of the periodontium, play a role in physiologic (e.g., tooth eruption) and pathologic (e.g., periodontitis) events. The evidence for the role of MMPs in periodontal destruction has accumulated over three and a half decades, and it is now recognized that an imbalance between activated MMPs and their endogenous inhibitors leads to pathologic breakdown of the extracellular matrix during periodontitis. This understanding has stimulated the search for a number of synthetic inhibitors that could be used as potential therapeutic agents. Tetracycline analogues, as proteinase inhibitors, are currently closer to being used clinically than any other agents in periodontal therapy. Other MMP inhibitors, such as Batimastat (British Bio-technology, Oxford, UK), are currently being tested clinically for inhibition of cancer metastasis and other diseases. Multiple mechanisms of MMP inhibition by tetracycline analogues have been proposed. The nonantimicrobial chemically modified tetracyclines are potent inhibitors of MMPs, preventing collagen breakdown and alveolar bone loss in animal models of periodontitis. In addition, nonantimicrobial low doses of the commercially available semisynthetic tetracycline doxycycline, have been used in human clinical trails to reduce MMP activity in the gingival crevicular fluid and gingival tissues, with a resultant reduction in pocket depth and attachment loss. Of particular interest, periodontal research on the nonantimicrobial properties of tetracycline has generated new therapeutic approaches to a variety of medical disorders characterized by excess MMP activity.

Alveolar Bone Loss↗

Obstruction to venous outflow from the left lower extremity after renal transplantation.

Three patients with acute massive swelling of the left lower extremity occurring soon after placement of a renal allograft in the left iliac fossa are described. In each patient, obstruction to venous outflow from the left lower limb was documented by venography. We surmise that venous obstruction resulted principally from a combination of extrinsic compression of the left iliac vein by the right common iliac artery or by the allograft, and enhanced venous return from the allograft.

Constriction, Pathologic↗

A survey of physician knowledge of drug costs.

Previous studies have indicated that physicians have inadequate knowledge of drug costs. This study was designed to determine actual pharmacy prices of 12 nonsteroidal anti-inflammatory drugs (NSAIDs) and physicians' knowledge of these prices. Pharmacists (N = 67) in a large urban area were surveyed to determine the lowest retail price of commonly prescribed medications. Pain clinic and orthopedic physicians (N = 95) were surveyed to determine their knowledge of prices for 12 NSAIDs. There was wide variation between pharmacies in the cost of medications. Eighty-one percent of physicians agreed that cost is an important factor to consider. Only 25% of physicians estimated at least one-half of the medications between the highest and lowest pharmacy price. The results of this study indicate that physicians need more information about prices of medications they prescribe.

Anti-Inflammatory Agents, Non-Steroidal↗

Intravenous regional guanethidine in the treatment of reflex sympathetic dystrophy/causalgia: a randomized, double-blind study. Guanethidine Study Group.

This double-blind, randomized, multicenter study was designed to determine the short-term and long-term efficacy of intravenous regional block with guanethidine in patients with reflex sympathetic dystrophy (RSD)/causalgia. Sixty patients were enrolled to receive four intravenous regional blocks at 4-day intervals with either guanethidine or placebo in 0.5% lidocaine. Each patient was randomized to receive either one, two, or four blocks with guanethidine. Follow-up visits were scheduled for 4 days, 1 mo, 3 mo, and 6 mo after their final block. At 4 days after the initial block, the group treated with placebo experienced a greater decrease in pain scores than those treated with guanethidine, although this difference was not statistically significant. On long-term followup there was no difference in pain scores between groups receiving one, two, or four guanethidine blocks. Overall, only 35% of patients experienced clinically significant relief on long-term followup even though all were treated early in the evolution of RSD.

Adult↗