Electrosprayed hydroxyapatite on polymer nanofibers to differentiate mesenchymal stem cells to osteogenesis.

Electrospraying of hydroxyapatite (HA) nanoparticles onto the surface of polymer nanofibers provides a potentially novel substrate for the adhesion, proliferation and differentiation of mesenchymal stem cells (MSCs) into bone tissue regeneration. HA nanoparticles (4%) were electrosprayed on the surface of electrospun polycaprolactone (PCL) nanofibers (420 ± 15 nm) for bone tissue engineering. PCL/HA nanofibers were comparatively characterized with PCL/Collagen (275 ± 56 nm) nanofibers by FT-IR analysis to confirm the presence of HA. Fabricated PCL/HA and PCL/Collagen nanofibers and TCP (control) were used for the differentiation of equine MSC into osteogenic lineages in the presence of DMEM/F12 medium supplemented with ß-glycerophosphate, ascorbic acid and dexamethasone. Cell proliferation and differentiation into an osteogenic lineage was evaluated by MTS assay, SEM observation, ALP activity, ARS staining, quantification of mineral deposition and expression of osteocalcin. Proliferation of MSCs increased significantly (P ⩽ 0.05) up to 12% in PCL/Collagen (day 15) compared to PCL/HA nanofibrous substrate. ALP activity was increased 20% in PCL/HA by day 10 confirming the direction of osteogenic lineage from MSCs differentiation. PCL/HA stimulated an increased mineral secretion up to 26% by day 15 on ARS staining compared to PCL/Collagen nanofibers and showing cuboidal morphology by expressing osteocalcin. These results confirmed that the specifically fabricated PCL/HA composite nanofibrous substrate enhanced the differentiation of MSCs into osteogenesis.

Continuous nanostructures for the controlled release of drugs.

The annual world wide market for controlled release of polymer systems which extends beyond drug delivery is now estimated to $60 billion and these systems are used by over 100 million people each year. It was estimated that drug delivery will play a pivotal role in approximately 40% of all pharmaceutical sales in near future. Novel methods of drug delivery will not only result in more effective and efficacious treatments but also generates new niche markets to provide greater intellectual property protection to already existing drug formulations. Recently, biodegradable electrospun polymer nanofibrous substrate as drug carrier seems to be a promising method for delivering anticancer drugs, especially in postoperative local chemotherapy. Alternatively drug release can be triggered by the environment or other external events such as changes in pH, temperature, or the presence of analyte such as glucose. In general, controlled release of polymer systems delivering drugs in the optimum dosage for long periods is to increase the efficacy of drug, reducing patient compliance. Recent research for the use of nanotechnology (nanoparticle and nanofibers) in drug delivery suggests that the technology might solve problems in the areas such as controlled release, various topical administration, gut absorption and targeted systemic delivery. This review article described the applications of polymer nanoparticles and nanofibers for loading potential drugs for the controlled release to target incurable diseases.

Variation in the histopathological features of patients with ascending aortic aneurysms: a study of 111 surgically excised cases.

BACKGROUND: Ascending aortic aneurysms (AA) are a common, though poorly understood medical condition. AIMS: To document the histological changes in a large series of human ascending AA, and to correlate these changes with clinical variables. METHODS: 111 ascending AA were excised at surgery over a 3 year period. Each aneurysm was received as a continuous ring of tissue. Sections were taken from the anterior, posterior, greater and lesser curvature of the aorta and graded in a semi-quantitative fashion for the degree of elastin fragmentation, elastin loss, smooth muscle cell (SMC) loss, intimal changes and inflammation. RESULTS: Mean patient age at surgery was 58.7 (15.6) years; there were 70 men and 41 women. 12 patients had Marfan syndrome, 34 (30.6%) had a bicuspid aortic valve (BAV), while 71 (64.0%) had a tricuspid aortic valve (TAV). Inflammatory cells were present in 28 cases (25.2%) and were confined to the adventitia. No particular region of the aortic circumference was more severely affected, however a BAV was associated with significantly less intimal change, and less fragmentation and loss of elastic tissue compared with patients with a TAV. Advanced age (>65 years), female gender and Marfan syndrome were all associated with more severe elastin degeneration and smooth muscle cell loss (p<0.05 for all). CONCLUSION: Results indicate a wide variation in the histological appearance in ascending AA, depending on patient characteristics. They suggest that the underlying aneurysm pathogenesis may also be highly variable; this warrants further investigation.

Sustained local drug delivery to the arterial wall via biodegradable microspheres.

This study was designed to evaluate the feasibility of applying locally delivered polylactic acid microspheres for drug delivery to the arterial wall. To study drug persistence, rhodamine-loaded microspheres were infused into one carotid artery of 14 rabbits and plain rhodamine solution into the other by using a porous balloon. To study tissue response, plain microspheres and dexamethasone-loaded microspheres were infused into the carotid arteries of another group of rabbits. To study the antiproliferative effects of locally delivered drug, 20 rabbits were subjected to overstretch balloon injury to both carotid arteries and divided into 4 groups: injury alone, plain microspheres, dexamethasone-loaded microspheres, and microspheres containing colchicine and dexamethasone. Fluorescent microspheres persisted in the vessel wall for 4 wk, whereas rhodamine without microspheres disappeared at 72 h. Histopathologic studies in arteries infused with unloaded microspheres showed inflammatory cell infiltrate with polymorphonuclear cells at 1 wk and macrophages and giant cells at 4 wk. Arteries infused with dexamethasone-loaded microspheres did not show any inflammatory cell infiltrate. Local delivery of dexamethasone or dexamethasone plus colchicine did not result in significant change in the intima-to-media ratio or in residual lumen following balloon injury. Polylactic acid microspheres may be used for prolonged delivery of drugs or other bioactive agents locally to the arterial wall. They induce an inflammatory reaction that is suppressable by dexamethasone in the microspheres. Dexamethasone or dexamethasone and colchicine delivered via this system, however, failed to reduce the degree of intimal hyperplasia after overstretch balloon injury to the rabbit carotid arteries.

Subacute thrombosis and vascular injury resulting from slotted-tube nitinol and stainless steel stents in a rabbit carotid artery model.

BACKGROUND: Our objectives were to quantify the thrombogenicity and extent of vascular injury created by slotted-tube geometry stainless steel and nitinol coronary stents in a rabbit carotid artery model. METHODS AND RESULTS: Stents were implanted in rabbit right carotid arteries without antiplatelet therapy. Stainless steel stents were implanted for 4 days while nitinol stents were placed for 4 and 14 days (n = 8, 8, and 6, respectively). Stent thrombosis was assessed by thrombus weight, grading thrombus encroachment of the lumen, and by blood flow in the stented and contralateral arteries. Stainless steel stents at 4 days contained more thrombus than 4- and 14-day nitinol stents (20.0 +/- 5.9 versus 2.5 +/- 0.6 and 2.7 +/- 0.3 mg, respectively; P < .000001). Stainless steel stents were more often occluded by thrombus (6 of 8) or contained more subocclusive thrombus (2 of 8) than nitinol stents (0 of 14, P < .002). Resting blood flow was reduced in arteries with stainless steel stents compared with 4- and 14-day nitinol stents (1.5 +/- 2.8 versus 24.0 +/- 2.0 and 25.5 +/- 1.9 mL/min, respectively, P < .000001). Stainless steel stents were less uniformly expanded, had deeper strut penetration into the vascular wall, and were associated with more extensive medial smooth muscle cell necrosis. There were strong correlations (r = .77 to .95) between variables of thrombosis extent (thrombus weight and grade) and histologically determined vascular injury (strut penetration and medial necrosis). CONCLUSIONS: Slotted-tube stainless steel stents were more thrombogenic and created more extensive vascular injury than nitinol stents in a rabbit carotid artery model. The mechanisms underlying these differences probably are related to metallurgic and design geometry properties of the two stent types.

A follow up study of major intimal dissections treated with perfusion balloon catheter.

Major intimal dissections during coronary angioplasty are an important cause of early morbidity and mortality. In the recent past various non-surgical modalities to manage such dissections have been developed. The choice of therapy among these needs knowledge not only of immediate success but also of long term results. Data on long term follow up of patients managed with prolonged balloon inflations using a perfusion balloon catheter is limited. We herein report our experience of twenty seven consecutive patients managed by prolonged dilatations using Stack perfusion balloon catheter. All the patients had a long dissection with luminal compromise, 6 (22%) had in addition an acute complete occlusion, and in 4 (15%) there was a thrombus. Only 6 (22%) needed an emergency CABG, with the remaining having an event free hospital stay. At follow up after 6-26 months, 7/21 (33%) had severe symptoms and 5 of them underwent coronary arteriography with four having a repeat successful dilatation. The findings of this study suggest that the perfusion balloon catheter is a useful modality for management of major dissections with a restenosis rate similar to that of primary PTCA. Randomised controlled trials are required to assess its efficacy vis a vis the newer therapeutic options like stents, lasers and atherectomy.

Echocardiographic diagnosis of aneurysm of the sinus of Valsalva.

Echocardiographic and Doppler data of 62 patients with ASOV are presented. Catheterization and angiography were performed in 38 cases and surgery in 25 of the 38. The origin of these aneurysms was the RCS in 56 cases, NCS in 5, and LCS in 1 case. Seven had unruptured aneurysms, 6 rising from RCS dissected into the ventricular septum, producing heart block in 4, AR in 5, mitral regurgitation in 1; 1 aneurysm rising from the LCS was asymptomatic. In other cases (n = 55) the aneurysm had ruptured into one of the cardiac chambers. Thirty-two of the 50 RCS aneurysms ruptured into the RVOT, 13 into the RV cavity, 2 into the RA, and 3 into the LV. Of the 5 NCS aneurysms, (3 ruptured into the RA, 1 into the RV, and 1 into both the RA and RV. Associated VSD was identified in 16 (25.8%) of 62 cases. All of these patients had RCS aneurysms that ruptured into the RVOT. Echocardiography missed VSD in three cases that at surgery were found to have VSD. AR was found in 34 of 62 cases. Echocardiography picked up discrete subaortic stenosis in two cases but missed subvalvar PS in 2 of the 3 cases. A detailed echocardiographic study (two-dimensional, Doppler, and color flow imaging) is accurate in the diagnosis of ASOV, in the identification of its site of origin and rupture, and in the evaluation of the associated defects; in the vast majority of cases, it can totally supplant the need for angiography.

Management of hepatic venous outflow obstruction.

Hepatic venous outflow obstruction (HVOO) is a rare cause of portal hypertension and conservative treatment is usually ineffective. A large series of patients gave us an opportunity to devise a management protocol for this disorder. Between 1978 and 1992, we prospectively studied 75 patients with HVOO. The obstruction was in the hepatic vein in 24, in the inferior vena cava (IVC) in 44, and in both in 7. For hepatic vein obstruction proximal splenorenal shunts were done in 7 (2 died postoperatively); 4 shunts blocked and only 1 patient became completely symptom free. In 2 patients with partial obstruction we performed balloon dilatation of the right hepatic veins but within 6 months the obstruction recurred. In the next 6 patients we constructed a side-to-side portocaval shunt; 2 died of encephalopathy after discharge and 4 are alive and well. For IVC obstruction, after surgical procedures had yielded poor results in 14 patients, we changed to balloon angioplasty which was successful in 28 of the 30 other patients; restenosis occurred in 4. Of the 7 patients with a combined block, 3 have had balloon angioplasty followed by a side-to-side portocaval shunt; 1 died, 2 are well, and the remainder have not completed treatment. Of our 75 patients, 22 have died (5 in hospital and 17 after discharge), 7 have not completed treatment, and 2 have been lost to follow-up. However, 44 are symptom free. We did not encounter any case of hepatocellular carcinoma. We suggest that patients with HVOO should be actively managed with a side-to-side portocaval shunt for hepatic vein obstruction, balloon angioplasty for inferior vena caval obstruction, and perhaps both procedures for those with combined obstructions.

Echocardiographic diagnosis of total anomalous pulmonary venous connection.

Over a 7-year period, 110 of 35,000 echocardiographic cases were diagnosed to have total anomalous pulmonary venous connection (TAPVC). Ages ranged from 7 days to 38 years (male 62, female, 48). In 60 cases the diagnosis was confirmed by angiography (n = 47) and/or surgery (n = 50). In 13 cases angiography was not performed; surgery was performed on the basis of echocardiographic diagnosis. Diagnosis of TAPVC was correctly made in all of the 60 confirmed cases. Drainage sites were correctly identified by echocardiography in 58 (96.7%) of these 60 cases. Of the five cases of mixed TAPVC, the second drainage site was missed by echocardiography in two cases. Of the 110 cases the drainage sites were as follows: supracardiac 70, cardiac 30, infracardiac 5, and mixed variety 5. Seventeen cases had Doppler echocardiographic evidence of obstruction along the course of the anomalous vein. The continuous wave Doppler signal for tricuspid regurgitation was present in 14 of 47 catheterized patients, and catheterization-measured peak pulmonary artery systolic pressure correlated well with that derived by Doppler study (r = 0.96, p = 0.001). Additionally, 17 patients had other cardiac anomalies that were correctly diagnosed by echocardiography. Combined two-dimensional and Doppler echocardiography is accurate in the diagnosis of TAPVC, identification of the site of drainage, presence of obstruction, and assessment of pulmonary arterial hypertension and other associated anomalies.

Chorionic villus sampling: quality control--a continuous improvement model.

OBJECTIVE: Our purpose was to describe Vanderbilt University Medical Center's experience in establishing a chorionic villus sampling program and the importance of quality control along with a continuous improvement model on the first 1000 cases. STUDY DESIGN: A continuous improvement model was established with emphasis on a multidisciplinary team approach and quality assurance process. A computerized data base was used for continuing analysis of complications and for allowing facile access to pertinent information. RESULTS: A continuous improvement model allowed for an improved process and outcome for patients, personnel, and referring health care providers. Follow-up for initial symptoms after chorionic villus sampling was obtained on 98.5% of patients. Pregnancy follow-up, including birth data, was obtained on 93%. CONCLUSION: A continuous improvement mode from the project's onset resulted in an improved process and outcome, information helpful for accessing spontaneous abortion rates and pregnancy outcomes (including the incidence of limb abnormalities and factors associated with abortions) and recommendations for training personnel.

Comparison of immediate hemodynamic response to closed mitral commissurotomy, single-balloon, and double-balloon mitral valvuloplasty in rheumatic mitral stenosis.

The hemodynamic response to closed mitral commissurotomy, single-balloon, and double-balloon mitral valvuloplasty was compared using 20 patients in each group. All patients had symptomatic rheumatic mitral stenosis with a mitral valve area < 1 cm2, without any left atrial clot, mitral valve calcification, or mitral regurgitation. There was a significant improvement in hemodynamics following intervention in all three groups. The mean pulmonary artery pressure decreased from 49.1 +/- 17.5 to 28.6 +/- 8.3 mm Hg (p < 0.001), 48.8 +/- 12.3 to 34.0 +/- 13.9 mm Hg (p < 0.001), and 46.7 +/- 18.0 to 26.3 +/- 13.7 mm Hg (p < 0.001) in the closed mitral commissurotomy, single-balloon, and double-balloon mitral valvuloplasty groups, respectively. The mitral valve area increased from 0.62 +/- 0.27 to 1.5 +/- 0.5 cm2 (p < 0.001), 0.68 +/- 0.24 to 1.5 +/- 0.4 cm2 (p < 0.001), and 0.68 +/- 0.25 to 1.9 +/- 0.8 cm2 (p < 0.001) in the closed mitral commissurotomy, single-balloon, and double-balloon mitral valvuloplasty groups, respectively. The increase in the mitral valve area was maximum in the group with double-balloon mitral valvuloplasty. In the closed mitral commissurotomy group there was a significant rise in left ventricular end-diastolic pressure, from 6.8 +/- 3.9 to 9.3 +/- 3.1 mm Hg (p < 0.001), but this remained unchanged in the single-balloon and double-balloon mitral valvuloplasty groups. Our study shows that single-balloon and double-balloon mitral valvuloplasty are comparable to closed mitral commissurotomy in the immediate hemodynamic response, with a larger valve area in the double-balloon mitral valvuloplasty group.

High-risk coronary angioplasty using percutaneous cardiopulmonary bypass support.

BACKGROUND: Balloon angioplasty has a high success rate but results in abrupt closure of the vessel in 2% to 6% of patients. This can lead to haemodynamic collapse and death, particularly if the patient has poor left ventricular function. In the event of abrupt closure of the coronary vessels, such patients may not survive long enough to undergo emergency bypass surgery. The prophylactic use of cardiopulmonary bypass to support patients at high-risk for angioplasty has been reported recently. We describe our initial experience with this technique. METHODS: Eighteen high-risk patients with severe angina were subjected to balloon angioplasty after instituting percutaneous cardiopulmonary bypass support to enhance the safety of high-risk elective coronary angioplasty. All patients had a low ejection fraction, a large amount of viable myocardium perfused by the targeted artery or both (left ventricular ejection fraction < 25% in 13 patients). Triple-vessel disease was present in all of them. Angioplasty of the only remaining vessel was done in 12 patients, 2 vessels in 5 patients and a sequential graft in 1 patient. Bypass flow ranged from 2.8 to 4.5 litres and was discontinued after a mean of 35 minutes. Haemostasis was achieved by external clamp compression in 16 patients. RESULTS: The angioplasty was successfully performed in all the patients and was well tolerated. During the bypass period, the pulmonary artery diastolic pressure ranged from 0 to 8 mmHg. There was no hospital death. Two patients required surgical exploration of the femoral artery puncture site--one because of poor distal perfusion and the other for continued bleeding. During the follow up period of 1 to 10 months, 11 patients were free of angina and 1 had died. CONCLUSION: Our experience confirms that percutaneous bypass support in selected patients undergoing high-risk coronary angioplasty is safe and effective.

Fish oil supplements for prevention of restenosis after coronary angioplasty.

We have evaluated the effect of fish oil supplementation in the prevention of restenosis after percutaneous transluminal coronary angioplasty by a randomised trial conducted in 107 patients. The treatment group (n = 58, 96 significant coronary narrowings) received 10 capsules of fish oil (1.8 g eicosapentaenoic acid, 1.2 g docosahexaenoic acid) besides aspirin and calcium blockers, beginning 4.3 (SD 2.9) days before coronary angioplasty. The conventional medical treatment group (n = 49, 81 significant coronary narrowings) received only aspirin and calcium blockers. Enrollment required the presence of angina pectoris and successful dilatation of all significant coronary narrowings. All patients were followed-up for at least 6 months. Restenosis was identified by symptoms and exercise testing and confirmed by angiography. The incidence of angiographic restenosis was 32% in the fish oil group and 27% in the conventional treatment group. Biochemical investigations showed a greater decrease in serum triglyceride levels in fish oil group as compared to the conventional treatment group. There was no significant difference in the cholesterol levels over the treatment period. Administration of fish oil in a dose of 3 g per day did not reduce the incidence of early restenosis after coronary angioplasty.

Immunosuppressive therapy in inflammatory myocarditis: long-term follow-up.

Sixteen patients (12 male and 4 female, age 2-46 years) with endomyocardial biopsy-proven myocarditis were prospectively evaluated with immunosuppressive therapy including azathioprine and prednisolone in addition to other standard measures. Patients were either in NYHA class IV (n = 12) or class III (n = 4). Twelve patients showed improvement and the remaining 4 continued to deteriorate: 2 died at 1 and 2 months after therapy and the other 2 were lost to follow-up after 4-6 weeks of therapy. Three of the 12 patients who showed significant improvement, after sudden omission of therapy (at 8 weeks, 6 and 8 months) worsened and died. One patient who showed significant improvement died suddenly after 9 months of therapy while playing football. The remaining patients have shown significant clinical and haemodynamic improvement with normalization of myocardial morphology. Serial haemodynamic studies revealed a significant fall in cardiothoracic ratio (before: 62.3 +/- 4.7%; 3 months: 55.1 +/- 3.1%, P less than 0.0001; 6-12 months: 50.6 +/- 1.5%, P less than 0.0001), mean pulmonary artery pressure (before: 34.3 +/- 13.05 mm; 3 months: 20.4 +/- 8.71 mm, P less than 0.01; 6-12 months: 20.0 +/- 2.75 mm, P less than 0.01) and mean pulmonary artery wedge pressure (before: 26.0 +/- 9.07 mm; 3 months 14.0 +/- 5.63 mm, P less than 0.001; 6-12 months: 13.2 +/- 4.57 mm, P less than 0.001). The left ventricular ejection fraction improved from 24.3 +/- 8.36% to 35.8 +/- 9.72% (P less than 0.001) at 3 months and 49.8 +/- 18.2% (P less than 0.0001) at 6-12 months of therapy. Two patients have been subsequently lost to follow-up whereas the remaining 6 patients are on follow-up for 1-4 years after therapy and are doing fine. Our uncontrolled observations suggest that immunosuppressive therapy may be useful in patients with inflammatory myocarditis.

Persistent atrial standstill--clinical, electrophysiological, and morphological study.

Persistent atrial standstill (PAS) is a rare disorder characterized by absence of atrial activity on the surface and intracavity electrograms, absence of atrial mechanical activity, and inability to electrically stimulate the atria. Four patients (ages 18-60 years) with PAS were evaluated. One of these (no. 3) only had right atrial (RA) standstill, whereas left atrium (LA) showed spontaneous activity and could be stimulated electrically. As RA biopsy is not possible, right ventricular (RV) endomyocardial biopsy (EMB) was obtained to identify possible atrial pathology that revealed inflammatory myocarditis, 2; amyloidosis, 1; and myocardial hypertrophy with fibrosis, 1. Three patients were given permanent pacemakers. One of these with amyloidosis died suddenly. One is lost to follow-up. The others cases are persisting with PAS.

Silent myocardial ischemia after percutaneous transluminal coronary angioplasty and its prognostic significance.

A cohort of 175 patients who underwent successful percutaneous transluminal coronary angioplasty (PTCA) were subjected to a treadmill exercise test to determine the prognostic significance of silent and symptomatic myocardial ischemia during the follow-up (average 11.7 months). The cardiac events during the follow-up were defined as cardiac death, nonfatal myocardial infarction, class III angina, and need for repeat angioplasty or coronary artery bypass surgery. During exercise, 39 patients (22%) had abnormal exercise-induced ST depression without chest pain (Group I). A group of 22 patients (13%) had both exercise-induced chest pain and ST-segment depression (Group II), and 114 patients (65%) had normal exercise test and no chest pain (Group III). The groups were similar in sex distribution, history of previous myocardial infarction, distribution of vessel disease, and presence of left ventricular dysfunction. Group III included more patients with complete revascularization. Follow-up data revealed that cardiac event rates in Groups I and II were significantly higher than in Group III (41%, 41%, vs. 16%) (p less than 0.01). The event rates in Groups I and II with multivessel angioplasty also were significantly higher than in Group III (58%, 61%, vs. 21%) (p less than 0.01). Exercise-induced silent myocardial ischemia is frequently seen early after successful PTCA and is more prevalent in patients undergoing multivessel angioplasty and incomplete revascularization. Both silent and symptomatic ischemia early after PTCA are predictors of an unfavorable prognosis.

The morphology of coronary arterial dissection occurring subsequent to angioplasty and its influence on acute complications.

We reviewed the records of 402 patients undergoing percutaneous transluminal coronary angioplasty to identify factors predicting an ischemic event with arterial disruption during an otherwise uncomplicated angioplasty. Major dissection of the coronary arteries without immediate occlusion was found in 25 patients, who exhibited 28 dissected lesions. Dissections were classified into 2 types: those producing a continuous extraluminal and parallel filling tract, and those with a continuous parallel filling tract extending into and compromising the lumen. Ischemic complications (defined as myocardial infarction, the need for repeat angioplasty, or coronary arterial bypass surgery) occurred in 6 patients (24%) within 24 hours of the completion of the procedure. The remaining 19 patients had an uncomplicated hospital course. Acute ischemic complications following dissection correlated with the percentage of luminal compromise 50 +/- 0% in those with complications as opposed to 17 +/- 21% in those without: P less than 0.001) and the development of dissection producing a filling tract which compromised at least half the lumen (100% in those with complications versus 9.1% in those without: P less than 0.001). There was a trend towards an increase in ischemic complications in patients with proximal and eccentric lesions. We conclude that patients who develop dissections which produce significant luminal compromise after an otherwise uncomplicated angioplasty are at a high risk of developing an acute ischemic complication within 24 hours of the procedure.

Idiotypic cross-reactivity of immunoglobulins expressed in Waldenström's macroglobulinemia, chronic lymphocytic leukemia, and mantle zone lymphocytes of secondary B-cell follicles.

Monoclonal antibodies (MoAbs) specific for autoantibody-associated cross-reactive idiotypes (CRIs) of Waldenström's IgM react frequently with the surface Ig (slg) expressed by leukemia cells of patients with chronic lymphocytic leukemia (CLL). Evaluation of the molecular basis for this cross-reactivity indicates that such CRIs are encoded by conserved antibody variable region genes (V genes) that have undergone little or no somatic hypermutation. We find that such anti-CRI MoAbs stain a subpopulation of cells within the mantle zones surrounding the germinal centers of normal human tonsil. In contrast, MoAbs specific for variable region subgroup determinants react with cells in both the mantle zones and germinal centers of secondary B-cell follicles. To test whether mantle zone B cells not reactive with existing anti-CRI MoAbs may express slg bearing as-yet-unrecognized CRIs present on Igs produced by neoplastic cells of some patients with Waldenström's macroglobulinemia or CLL, we immunized mice with purified Waldenström's IgM that have been characterized for their variable region subgroups using subgroup-specific antisera raised against synthetic peptides. The supernatants of hybridomas generated from the splenocytes of immunized mice were screened for their ability to stain a subpopulation of mantle zone lymphocytes in human tonsil. With this approach, two new anti-CRI MoAbs were identified, designated OAK1 and VOH3. OAK1 binds to a CRI present on a subset of kappa light chains of the VK1 subgroup. VOH3 recognizes a CRI determinant(s) present on a subset of antibody heavy chains of the VH3 subgroup. Flow cytometric analyses demonstrated that OAK1 specifically binds leukemia cells from 5 to 20 patients (25%) with kappa light chain expressing CLL. In addition, VOH3 reacted with the leukemia cells from 1 of 17 (6%) patients tested. The success of these methods demonstrates that the variable regions of the Igs produced by mantle zone B cells share idiotypic determinants with Igs expressed in B-cell CLL (B-CLL) and Waldenström's macroglobulinemia.

Profile of coronary artery disease in Indian women: correlation of clinical, non invasive and coronary angiographic findings.

Clinical and risk factor profile of 101 consecutive female patients subjected to coronary angiography was analysed. Coronary angiography showed single vessel disease (SVD) in 15.8 per cent, double vessel disease (DVD) in 12.9 per cent, triple vessel disease (TVD) in 39.6 per cent and normal coronary arteries (NC) in 30.7 per cent. Risk factor profile in patients with angiographic coronary artery disease (group II) included hypertension (HT) in 52.9 per cent, diabetes mellitus (DM) in 44.3 per cent, post menopausal state in 84.3 per cent, positive family history in 51.4 per cent, obesity in 58.3 per cent, low density and high density lipoprotein ratio (LDL/HDL) more than 3.0 in 58 per cent and smoking in 4.3 per cent. Risk factors in 31 patients with NC (group I) included HT in 29 per cent, DM in 6.5 per cent, positive family history in 45.2 per cent, obesity in 45.2 per cent, post menopausal state in 48.4 per cent, LDL/HDL ratio more than 3.0 in 30 per cent and smoking in none. The clinical presentation in group II was unstable angina in 64.3 per cent, stable angina pectoris in 24.3 per cent, myocardial infarction in 4.3 per cent and atypical chest pain in 2.8 per cent. In group I half the patients presented with atypical chest pain. The other modes of presentation included unstable angina 25.8 per cent, stable angina pectoris in 16.2 per cent and myocardial infarction in 6.5 per cent. Predictive value of exercise electrocardiography (Ex ECG) or exercise radionuclide studies (Ex RNU) was 61.7 and 68.4 per cent respectively. DM, post-menopausal state and LDL/HDL ratio more than 3 were significant risk factors in women.(ABSTRACT TRUNCATED AT 250 WORDS)