Dynamic Magnetic Resonance Imaging- a sensitive tool in managing consecutive exotropia.

BACKGROUND: Proper evaluation and accurate diagnosis are crucial in managing a case of strabismus. OBJECTIVE: Report a case of prolonged large angle complicated consecutive exotropia where dynamic Magnetic Resonance Imaging helped us to diagnose and simplify the management plan. CASE: A 19-year-old male presented with outward deviation of both eyes for last 16 years with right face turn, without diplopia and trauma. However, he had history of two consecutive squint surgeries, a month apart, at the age of 3 years. OBSERVATION: Visual acuity (best corrected) in the right and left eye was 6/36 and 6/6 respectively. Extraocular movements revealed minus (-) 4 adduction deficits in the left eye with right eye suppression. Prism Alternate Cover Test (PACT) showed 65 prism diopter (PD) base in (BI), for primary and near gazes with lateral incommitance and without any pattern. Forced Duction Test (FDT) showed restriction of the left lateral rectus. Dynamic Magnetic Resonance Imaging revealed posterior insertion of the left medial rectus with thinning of the tendinous insertion of the left lateral and medial rectus in neutral position. On adduction of left eye, there was slight increased bulk of the left medial rectus. Medial Rectus (MR) advancement 5.5 mm and Lateral Rectus (LR) recession 9mm was done. Repeat FDT showed improvement in resistance. After 3 month, the patient had excellent outcome with 5 PD primary position exotropia and 2 units of improvement in left eye adduction. CONCLUSION: Precise workup and appropriate investigation decreases the undue interventions with excellent outcome in a case of large angle consecutive XT. Keywords Consecutive exotropia; dynamic MRI; esotropia; medial rectus advancement; slipped muscle.

Hazardous drinking and its association with homelessness among veterans in care.

BACKGROUND: While scholarship on alcohol use and homelessness has focused on the impact of alcohol abuse and dependence, little is known about the effects of lower levels of misuse such as hazardous use. Veterans receiving care in the Department of Veterans Affairs Health Care System (VA) constitute a population that is vulnerable to alcohol misuse and homelessness. This research examines the effects of hazardous drinking on homelessness in the Veterans Aging Cohort Study, a sample of 2898 older veterans (mean age=50.2), receiving care in 8 VAs across the country. METHODS: Logistic regression models examined the associations between (1) hazardous drinking at baseline and homelessness at 1-year follow-up, (2) transitions into and out of hazardous drinking from baseline to follow-up and homelessness at follow-up, and (3) transitioning to hazardous drinking and transitioning to homelessness from baseline to follow-up during that same time-period. RESULTS: After controlling for other correlates including alcohol dependence, hazardous drinking at baseline increased the risk of homelessness at follow-up (adjusted odds ratio [AOR]=1.39, 95% confidence interval [CI]=1.02, 1.88). Transitioning to hazardous drinking more than doubled the risk of homelessness at follow-up (AOR=2.42, 95% CI=1.41, 4.15), while more than doubling the risk of transitioning from being housed at baseline to being homeless at follow-up (AOR=2.49, 95% CI=1.30, 4.79). CONCLUSIONS: Early intervention that seeks to prevent transitioning into hazardous drinking could increase housing stability among veterans. Brief interventions which have been shown to be effective at lower levels of alcohol use should be implemented with veterans in VA care.

Delayed occurrence of restenosis in drug eluting stents: an evidence of delayed healing.

Drug eluting stents have made a significant impact on restenosis. However, there are concerns regarding delayed "catch-up" of restenosis. In this case report we present two such patients with delayed occurrence of restenosis after drug eluting stent implantation.

Coronary stent implantation without lesion predilatation (direct stenting): our experience with this evolving technique.

BACKGROUND: Until recently, conventional intracoronary stent deployment required predilatation of the lesion with a balloon. However, "direct stenting" of the lesion without predilatation offers certain theoretical and practical advantages. We assessed the safety and feasibility of direct stenting in a select group of patients who were likely to benefit most from these advantages, namely, those with acute coronary syndromes. saphenous vein graft lesions, associated renal or left ventricular dysfunction and those requiring multivessel intervention. METHODS AND RESULTS: After direct stenting, intravascular ultrasound was used to assess the adequacy of stent expansion in 51 patients. One hundred and twenty patients with a total of 125 lesions (83.3% males, average age 54.6+/-12.4 years) were enrolled for direct stenting. Of these, 90% of patients had presented with acute coronary syndromes, 21.6% of patients had associated moderate-to-severe left ventricular systolic dysfunction, 6.7% of patients had associated renal dysfunction and 30.8% of patients required multivessel intervention. Angiographically visible thrombus was present in 35.2% of patients. The mean reference diameter of the lesion was 3.18+/-0.32 mm and mean percentage diameter stenosis was 76.4+/-11.2%. Almost all varieties of stents were used (8.8% bare and 91.2% mounted). Procedural success was achieved in 98.3% of patients (98.4% of lesions). In two cases, the lesion had to be predilated prior to stenting. On angiography, the need for postdilatation of the stent was apparent in 29 (23.6%) lesions. In contrast, on intravascular ultrasound evaluation done in 51 lesions after stent deployment, the need for postdilatation to optimize stent expansion was seen in 43 (84.3%) lesions. There was one instance of acute stent thrombosis and two instances of slow-flow phenomenon. There were no deaths, myocardial infarction or need for urgent bypass surgery. CONCLUSIONS: We conclude that direct stenting is feasible and safe in selected groups of patients. Optimization of stent expansion after direct stenting may often require aggressive postdilatation.

Development of biotechnology in India.

India has embarked upon a very ambitious program in biotechnology with a view to harnessing its available human and unlimited biodiversity resources. It has mainly been a government sponsored effort with very little private industry participation in investment. The Department of Biotechnology (DBT) established under the Ministry of Science and Technology in 1986 was the major instrument of action to bring together most talents, material resources, and budgetary provisions. It began sponsoring research in molecular biology, agricultural and medical sciences, plant and animal tissue culture, biofertilizers and biopesticides, environment, human genetics, microbial technology, and bioprocess engineering, etc. The establishment of a number of world class bioscience research institutes and provision of large research grants to some existing universities helped in developing specialized centres of biotechnology. Besides DBT, the Department of Science & Technology (DST), also under the Ministry of S&T, sponsors research at universities working in the basic areas of life sciences. Ministry of Education's most pioneering effort was instrumental in the creation of Biochemical Engineering Research Centre at IIT Delhi with substantial assistance from the Swiss Federal Institute of Technology, Zurich, Switzerland to make available state-of-the-art infrastructure for education, training, and research in biochemical engineering and biotechnology in 1974. This initiative catalysed biotechnology training and research at many institutions a few years later. With a brief introduction, the major thrust areas of biotechnology development in India have been reviewed in this India Paper which include education and training, agricultural biotechnology, biofertilizers and biopesticides, tissue culture for tree and woody species, medicinal and aromatic plants, biodiversity conservation and environment, vaccine development, animal, aquaculture, seri and food biotechnology, microbial technology, industrial biotechnology, biochemical engineering and associated activities such as creation of biotechnology information system and national repositories. Current status of intellectual property rights has also been discussed. Contribution to the India's advances in biotechnology by the industry, excepting a limited few, has been far below expectations. The review concludes with some cautious notes.

Multi-vessel coronary stenting--procedural results and late clinical outcomes: a comparison with single-vessel stenting.

The purpose of this study was to assess the 1-year clinical outcome of patients with multi-vessel coronary artery disease (CAD) who underwent coronary stenting, and to compare the results with single-vessel coronary stenting carried out during the same period. We evaluated the in-hospital and 12-month clinical outcomes [death, Q-wave myocardial infarction (MI) and repeat revascularization rates at one year] in 384 consecutive patients treated with coronary stents in 2 (92% of patients) or 3 of the native coronary arteries and compared the outcome to 624 consecutive patients undergoing stenting in a single coronary artery between January 1, 1997 and January 31, 1999. The overall procedural success was obtained in 99% of patients with 2- or 3-vessel stenting and 98% of patients with single-vessel stenting. Procedural complications were similar (2.9% vs 2.6%; p = 0.12). During follow-up, target lesion revascularization was 16% in multi-vessel and 14% in single-vessel stenting (p = 0.38) and repeat revascularization was also similar for both groups (19% vs. 20%; p = 0.73). There was no difference in death (0.8% vs. 1.3%; p = 0.31) and Q-wave MI (0.7% vs. 1.4%; p = 0. 16) in the 2 groups. Overall cardiac event-free survival was similar for both groups (76% vs. 78%; p = 0.54). Multi-vessel stenting in carefully selected patients in our experience had a high procedural success with very low complication rates. The one-year clinical outcomes were acceptable and were similar to the results of single-vessel stenting.

Percutaneous transluminal myocardial revascularization with a holmium laser system: procedural results and early clinical outcome.

Surgical transmyocardial laser revascularization has been reported to improve clinical outcome in patients with refractory angina who are not candidates for angioplasty or bypass surgery. We investigated the feasibility and safety of a nonsurgical, percutaneous technique for laser channel creation using energy from a holmium:yttrium-aluminium-garnet (YAG) laser. The laser energy was directed through a fiber enclosed in a catheter to the ventricular myocardium creating channels between the blood pool and the myocardium. Thirty-five patients with angina and coronary anatomy not amenable to revascularization with coronary angioplasty or bypass surgery underwent percutaneous transluminal myocardial revascularization. A total of 15 +/- 5 channels were formed per patient. There was no procedure-related mortality. One patient developed cardiac tamponade requiring thoracotomy and another a minor self-limiting pericardial effusion. There was no worsening of regional wall motion function in any patient. All patients were discharged alive after a postprocedure hospital stay of 2.1 +/- 1.4 days. Mean Canadian Cardiovascular Society (CCS) functional class declined from 3.68 +/- 0.4 before procedure to 0.82 +/- 0.7 at 30 days (P < 0.01). At 3 months, mean angina class was 0.94 +/- 0.65 (n = 35; P < 0.01) and at 6 months, mean angina class was 1.08 +/- 0.58 (n = 26; P < 0.01). One patient required repeat revascularization after 5 months for progression of disease in a degenerated saphenous venous graft supplying different region of myocardium. We conclude that transmyocardial revascularization using holmium:YAG laser by percutaneous technique can be carried out safely with encouraging early results and a very low complication rate. The symptomatic relief seen up to 6 months has been excellent. The long-term effects of this technique on mortality and relief of angina, however, remain to be defined. Cathet. Cardiovasc. Intervent. 47:287-291, 1999.

Primary stenting in acute myocardial infarction: a 30-day follow up study.

Primary coronary stenting is being increasingly used in patients undergoing primary coronary angioplasty for acute myocardial infarction. In this prospective study we evaluated our experience of direct angioplasty in 68 patients with acute myocardial infarction of whom 57 received intracoronary stents using high-pressure deployment (> or =12 atmospheres) with adjunct aspirin and ticlopidine therapy without coumadin. All patients underwent pre-discharge follow-up angiography. Stent implantation was successful in all patients. Stent thrombosis was not seen in any patient. However, TIMI grade 3 flow was obtained in only 51 patients (89.6%) with evidence of slow flow present in remaining six patients. Follow-up angiograms showed no stent thrombosis but five out of the six patients (83%) with slow-flow phenomenon persisted to have slow flow. These patients had lower left ventricular ejection fraction as compared to patients with TIMI 3 flow at follow-up angiography (27.5 +/- 10.2% vs. 42.1 +/- 15.2%, P < .001) and a high mortality (two out of six) within 30 days. Primary stenting is safe and feasible in the majority of patients with good short-term outcomes, but persistent slow-flow phenomenon with adverse clinical outcome is seen in a small but significant number of patients.

Outcomes of primary stenting for acute myocardial infarction.

Primary coronary stenting is being increasingly used in patients undergoing primary coronary angioplasty for acute myocardial infarction. In this prospective study we analysed our experience of direct angioplasty in 76 patients with acute myocardial infarction of whom 65 received intracoronary stents using high pressure deployment (> or = 12 atm) with adjunctive aspirin and ticlopidine therapy but without coumadin. All patients underwent pre-discharge angiography. Stent implantation was successful in all patients. Stent thrombosis was not seen in any patient. However, TIMI grade 3 flow was obtained in only 58 (89.2%) patients with evidence of slow-flow present in the remaining seven patients. Pre-discharge angiograms showed no-stent thrombosis but five out of the seven (71%) patients with slow-flow phenomenon persisted to have slow-flow. These patients had lower left ventricular ejection fraction as compared to patients with TIMI 3 flow at pre-discharge angiography (27.5 +/- 10.2% vs 42.1 +/- 15.2%; p < 0.001) and a high mortality (2 out of 7) within 30 days. Primary stenting is safe and feasible in the majority of patients with good short-term outcome. But persistent slow-flow phenomenon with adverse clinical outcome is seen in a small but significant number of patients.

Intravascular Red Light Therapy after Coronary Stenting Ñ Angiographic and Clinical Follow-up Study in Humans.

In animal models of coronary restenosis, intravascular red light therapy (IRLT) using a diode laser source has been shown to reduce neointimal hyperplasia following balloon-induced injury and coronary stenting. We studied the safety and efficacy of catheter-based IRLT for preventing restenosis after coronary stenting in 22 patients with angina pectoris. IRLT was performed using a diode laser (650 nm) at an energy level of 10 megawatts delivered through a rapid exchange balloon system containing the fiberoptics. The procedure was successful in all patients, with no procedural or in-hospital complications. Two patients with recurrence of symptoms had angiography at 3 and 4.1 months respectively. Angiographic follow-up was also done after 6 months in the 20 remaining asymptomatic patients. The mean minimal lumen diameter (MLD) for the whole group at 6 months follow-up was 2.57 +/- 0.62 mm. The calculated late lumen loss was 0.49 +/- 1.12 mm with a late loss index of 0.21 +/- 0.54. Four patients (2 symptomatic and 2 asymptomatic) in the series developed angiographic restenosis. Clinical events at follow-up of 10.9 +/- 3.5 months were repeat angioplasty in 2 patients for symptomatic restenosis with a 91% event free survival. These preliminary results demonstrate that IRLT after coronary artery stenting is safe and feasible; it is associated with low rates of angiographic indices of restenosis.

Heart in hypothyroidism--an echocardiographic study.

55 individuals, 44 of whom served as patients and 11 as controls were included in this study. Patient group was further divided into overt and subclinical hypothyroid group each having 22 patients. Patients were examined in a prospective manner and results compared with control group with an aim to evaluate the effect of hypothyroidism subclinical and overt on cardiac status by echocardiography. Variables of heart structure and function were assessed by cross sectional and Doppler echocardiography. IVS dimensions were significantly raised in moderate subclinical and in severe overt hypothyroidism (mean 0.911 +/- 0.038 and 0.973 +/- 0.217 cm). LVPW thickness was significantly increased only in overt hypothyroidism (mean 1.378 +/- 0.246). However RVW and LVID showed no definite pattern of change. Pericardial effusion and Diastolic dysfunction was seen in significant cases only in overt hypothyroidism. To conclude, hypothyroidism both subclinical and overt is associated with cardiovascular alteration both structural and functional. IVS and LVPW thickness are markedly affected, as well as there is impairment of left ventricular function more in diastole.

Inhibition of Epstein-Barr-virus-transformed human chronic lymphocytic leukaemic B cells with monoclonal-antibody-adriamycin (doxorubicin) conjugates.

The anthracyclin antineoplastic agent doxorubicin (Adriamycin) was linked by four different methods of linkage to DalB02, an IgG1 kappa murine monoclonal antibody (mAb) against surface-associated antigens on human chronic lymphocytic leukaemia (CLL) B cells. All the four conjugates fully retained the immunoreactivity of the parent DalB02. When the inhibitory effect of these conjugates was evaluated in vitro against the target D10-1 cells (a clone derived from an Epstein-Barr-virus-transformed human CLL B cell line that binds DalB02) it was observed that one conjugate was more potent than the free drug but the others were not. When 131I-labelled unmodified DalB02 and the 131I-labelled DalB02-containing conjugate that was found to be potent were injected i.v. into nude mice bearing a subcutaneous D10-1 xenograft, the percentages of the injected dose (%ID) of both 131I-DalB02 and the 131I-DalB02-containing conjugate that localized in the tumour were much higher than the %ID of the respective preparations that localized in normal tissues of D10-1-xenografted mice. The systemic toxicity of the conjugate was less than that of the free drug. At an equitoxic dose level, this conjugate was a more effective inhibitor of established D10-1 xenografts than the free drug.

An analysis of the relative activities of a number of promoter constructs from genes which are expressed during late pollen development as determined by particle bombardment.

The promoters of a tobacco actin gene, a tobacco pectate lyase, a tobacco and maize polygalacturonase and aBrassica S-locus related gene have been fused to theß-glucuronidase reporter gene and their activities determined by biolistic transient assay in tobacco pollen. In stably transformed tobacco all the transgenes with the exception of Cauliflower Mosaic Virus-35S-ß-glucuronidase appear to express efficiently in maturing pollen. Transient assay analysis showed that the tobacco pectate lyase and the polygalacturonase constructs were 8x more active than the tobacco actin construct, and that the tobacco polygalacturonase construct was some 33x more active than the maize polygalacturonase construct. Constructional manipulations that altered the lengths of the 5'-untranslated leaders including one which resulted in the removal of a 490 bp leader intron had little effect on the observed level of expression. However, the alteration of the context of the ATG from A/TnnATGG to CnnATGT resulting in a 70% reduction in the observed levels of activity, was obtained with the pectate lyase and polygalacturonase promoters. An identical reductional was also observed in transgenic plant populations transformed with the polygalacturonase transgenes.

Synthesis and characterization of carbohydrate-linked murine monoclonal antibody K20-human serum albumin conjugates.

Efficacy of antibody mediated targeting depends on retention of immunoreactivity in conjugates. Retention can be improved by site-specific linkage of drugs or drug-loaded carriers to residues that are located well away from the antigen-binding sites. In this study we describe the site-specific linkage of a potential drug carrier, human serum albumin (HSA), to the carbohydrate residues in Dal K20, a murine IgG1 monoclonal antibody (mAb) against human renal cell carcinoma, using disulfide exchange between 3-(2-pyridyldithio)propionic acid succinimidyl ester (SPDP)-derivatized HSA and 11-[[3-(2-pyridyldithio)propionyl]amino]undecanoic acid hydrazide (AUPDP)-derivatized mAb Dal K20. AUPDP gave a higher yield of the conjugate than a functionally analogous 3-(2-pyridyldithio)propionic acid hydrazide (HPDP), suggesting that the extra length of the former facilitated the linkage. The conjugates were found to be unstable without reduction of the hydrazone linkage using sodium cyanoborohydride. Stabilized 1:1 HSA:K20 carbohydrate-linked conjugates were isolated and compared with non-site-specific 1:1 conjugates in which HSA was conjugated to amino groups in mAb Dal K20. The yield and stability of the two conjugates were comparable, but the site-specific conjugate was found to retain three times more antibody activity than the non-site-specific conjugate.

Tumor localization and therapeutic potential of an antitumor-anti-CD3 heteroconjugate antibody in human renal cell carcinoma xenograft models.

A heteroconjugate (HC) antibody, constructed with the monoclonal antibody (MoAB) Dal K29 to human renal cell carcinoma (RCC) and an anti-CD3 MoAb, could induce a very high level of lysis of human RCC cells when incubated with human peripheral blood lymphocytes (PBL) in vitro (Kerr et al., 1990, J. Immunol., 144, 4060-4067). We now report that this HC antibody selectively localizes in RCC xenografts in nude mice and could inhibit RCC in an ascites tumor xenograft model when administered intraperitoneally together with PBL.