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The ‘Sepsis Six’ bundle was promoted as a deliverable tool outside of the critical care settings, but there is very little data available on the progress and change of sepsis care outside the critical care environment in the UK. Our aim was to compare the yearly prevalence, outcome and the Sepsis Six bundle compliance in patients at risk of mortality from sepsis in non-intensive care environments. Patients with a National Early Warning Score (NEWS) of 3 or above and suspected or proven infection were enrolled into four yearly 24-h point prevalence studies, carried out in fourteen hospitals across Wales from 2016 to 2019. We followed up patients to 30 days between 2016–2019 and to 90 days between 2017 and 2019. Out of the 26,947 patients screened 1651 fulfilled inclusion criteria and were recruited. The full ‘Sepsis Six’ care bundle was completed on 223 (14.0%) occasions, with no significant difference between the years. On 190 (11.5%) occasions none of the bundle elements were completed. There was no significant correlation between bundle element compliance, NEWS or year of study. One hundred and seventy (10.7%) patients were seen by critical care outreach; the ‘Sepsis Six’ bundle was completed significantly more often in this group (54/170, 32.0%) than for patients who were not reviewed by critical care outreach (168/1385, 11.6%; p Trial registration Defining Sepsis on the Wards ISRCTN 86502304 https://doi.org/10.1186/ISRCTN86502304 prospectively registered 09/05/2016.

Background & objectives: Acute myocardial infarction (AMI) is characterized by irreparable and irreversible loss of cardiac myocytes. Despite major advances in the management of AMI, a large number of patients are left with reduced left ventricular ejection fraction (LVEF), which is a major determinant of short and long term morbidity and mortality. A review of 33 randomized control trials has shown varying improvement in left ventricular (LV) function in patients receiving stem cells compared to standard medical therapy. Most trials had small sample size and were underpowered. This phase III prospective, open labelled, randomized multicenteric trial was undertaken to evaluate the efficacy in improving the LVEF over a period of six months, after injecting a predefined dose of 5-10 Χ 10 [8] autologous mononuclear cells (MNC) by intra-coronary route, in patients, one to three weeks post ST elevation AMI, in addition to the standard medical therapy. Methods: In this phase III prospective, multicentric trial 250 patients with AMI were included and randomized into stem cell therapy (SCT) and non SCT groups. All patients were followed up for six months. Patients with AMI having left ventricular ejection fraction (LVEF) of 20-50 per cent were included and were randomized to receive intracoronary stem cell infusion after successfully completing percutaneous coronary intervention (PCI). Results: On intention-to-treat analysis the infusion of MNCs had no positive impact on LVEF improvement of ≥ 5 per cent. The improvement in LVEF after six months was 5.17 ± 8.90 per cent in non SCT group and 4.82 ± 10.32 per cent in SCT group. The adverse effects were comparable in both the groups. On post hoc analysis it was noted that the cell dose had a positive impact when infused in the dose of ≥ 5 X 10 [8] (n=71). This benefit was noted upto three weeks post AMI. There were 38 trial deviates in the SCT group which was a limitation of the study. Interpretation & conclusions:Infusion of stem cells was found to have no benefit in ST elevation AMI. However, the procedure was safe. A possible benefit was seen when the predefined cell dose was administered which was noted upto three weeks post AMI, but this was not significant and needs confirmation by larger trials.

Background: The Trauma Expectation Factor Trauma Outcomes Measure (TEFTOM) questionnaire is a self-administered, patient-rated outcome measurement questionnaire designed to measure both ‘expectation’ and ‘outcome’ in orthopaedic trauma patients using two subsets of 10 items. We aimed to validate this instrument in a culturally diverse cohort of patients recruited from Asian and European regions. Methods: A total of 193 adult patients with surgically treated AO Foundation/Orthopaedic Trauma Association types 43 and 44 ankle malleolar and distal tibia fractures were recruited with 158 followed up till 1 year. Expectations were assessed prior to surgery, at 2 weeks and after 6 months using the trauma expectation factor (TEF) score. Outcomes were evaluated at 2 weeks, 6 and 12 months using the trauma outcome measure (TOM), American Academy of Orthopaedic Surgeons (AAOS), foot and ankle outcome score (FAOS) and short form-36 (SF-36) questionnaires. Psychometric properties of TEFTOM were assessed. Results: TEF and TOM demonstrated good internal consistency (Cronbach’s α > 0.87) and reliability at all time points (intra-class correlation coefficients > 0.90). TOM showed strong correlations ( R 2 ≥ 0.60) with the AAOS foot and ankle score, all FAOS subscales, except ‘symptoms’ and SF-36 physical functioning, role physical, bodily pain, social functioning and the physical component summary at 6 and 12 months. Effect sizes for TOM were 2.30 and 0.74 from 2 weeks to 6 months and from 6 months to 12 months, respectively. The baseline patient TEF was predictive for the 1-year TOM score. Conclusions: TEFTOM demonstrated good psychometric properties in this cohort of patients with ankle fractures. The TEF ‘expectation’ score was predictive of the TOM ‘outcome’ score. We recommend researchers and clinicians to utilize TEFTOM when patient expectation measurement is concerned for orthopaedic trauma patients.

The clinical presentation of hantavirus infections in India is unclear. We report here a case of hantavirus infection in a 46 year old quarry worker presenting with fever, abdominal pain, jaundice, thrombocytopenia and renal dysfunction. Seroconversion and rising anti-hantavirus IgG titers were taken as evidence of hantavirus infection. Clinicians should consider hantavirus infections in the differential diagnosis of acute febrile illness along with scrub typhus, leptospirosis and dengue.

Micro catheter tubes were prepared from poly (carbonate urethane) (PCU, Bionate) and poly (ether urethane) (PEU, Pellethane) and their stability was investigated in vitro under applied strain. The tubes were stretched to an elongation of 200% or 300% and exposed to hydrogen peroxide/cobalt chloride (H(2)O(2)/CoCl(2)) solution for specific periods of time (up to 10 months). The samples were observed for surface degradation via scanning electron microscopy, the bulk erosion via the weight difference, and the changes in molecular weight using gel permeation chromatography. The 200% and 300% strained Pellethane tubes kept in H(2)O(2)/CoCl(2) solution for 1 month showed substantial cracking of the surface layer with pitting and have degraded completely within 45 to 60 days (from scanning electron microscopy). Bionate tubes treated in similar conditions for a 10-month period exhibited minute surface erosion in the depth of 0.25-1 microm and showed no evidence of major cracking or pitting. The gel permeation chromatography analysis of 300% strained catheters indicated that the degradation of Bionate tubes was negligible. The 10-month samples had shown approximately 18% reduction in their number average molecular weight (M(n)) and about 8% reduction in weight average molecular weight (M(w)). The Pellethane studied in similar conditions had indicated approximately 72% reduction in M(n) and about approximately 50% reduction in M(w) for 1 month. Overall, the Bionate underwent less degradation and the degradated surface layer was much thinner than Pellethane. These in vitro results are valuable in designing the in vivo studies for using Bionate tube as a long-term implant.

Aims To characterize the atrial remodelling in mitral stenosis (MS). Methods and results Twenty-four patients with severe MS undergoing commissurotomy and 24 controls were studied. Electrophysiological evaluation was performed in 12 patients in each group by positioning multi-electrode catheters in both atria to determine the following: effective refractory period (ERP) at 10 sites at 600 and 450 ms; conduction time; conduction delay at the crista terminalis (CT); and vulnerability for atrial fibrillation (AF). P-wave duration (PWD) was determined on the surface ECG. In the remaining 12 patients in each group, electroanatomic maps of both atria were created to determine conduction velocity and identify regions of low voltage and electrical silence. Patients with MS had larger left atria (LA) ( P < 0.0001); prolonged PWD ( P = 0.0007); prolonged ERP in both LA ( P < 0.0001) and right atria (RA) ( P < 0.0001); reduced conduction velocity in the LA ( P = 0.009) and RA ( P < 0.0001); greater number ( P < 0.0001) and duration ( P < 0.0001) of bipoles along the CT with delayed conduction; lower atrial voltage in the LA ( P < 0.0001) and RA ( P < 0.0001); and more frequent electrical scar ( P = 0.001) compared with controls. Five of twelve with MS and none of the controls developed AF with extra-stimulus ( P = 0.02). Conclusion Atrial remodelling in MS is characterized by LA enlargement, loss of myocardium, and scarring associated with widespread and site-specific conduction abnormalities and no change or an increase in ERP. These abnormalities were associated with a heightened inducibility of AF.

The development of suitable three-dimensional matrices for the maintenance of cellular viability and differentiation is critical for applications in tissue engineering and cell biology. To this end, gel matrices of different proportions of alginate/elastin/polyethylene glycol (Alg/Ela/PEG) were prepared and examined. The composite matrix membranes were evaluated for their porous scaffold using SEM, enzymatic degradation and water content. An equal blend of Alg/Ela with a ratio of Alg/Ela: PEG (7:3) was selected for fabricating Alg/Ela/PEG scaffolds for this study. The Alg/Ela/PEG membranes fabricated at 20 degrees C and - 20 degrees C had a mean surface pore size of 35-45 microm. However, their ultrastructures had shown bigger pore structures (60-75 microm) compared to their surface. It is interesting to note that the membranes of Alg/Ela/PEG prepared at 20 degrees C had larger ultrastructural pores than that of membranes prepared at -20 degrees C. Further, the SEM studies revealed that in the absence of PEG the composite membranes of Alg/Ela formed with less porous structures. The water content of membranes prepared at 20 degrees C was higher with Alg/Ela/PEG (61.6 +/- 4.8%), compared to Alg/Ela (49.9 +/- 0.3%). The enzymatic degradation and water content studies also revealed that the membranes fabricated at - 20 degrees C had high water uptake and low enzymatic degradation, as that of the membranes prepared at 20 degreees C. In other words the larger pore structured membranes had less water content and high degradation profile. This study proposes that this novel composite matrix produces a hierarchical structure that is useful for generating tissue scaffolds for repairing the failing cardiac muscles. However, more detailed investigations with cytocompatibility studies are needed to find applications.

Heparin remains the gold-standard inhibitor of the process involved in the vascular response to injury. Continued anticoagulation is achieved by subcutaneous administration of low-molecular-weight heparin (LMW Hep) or with an orally active anticoagulant such as warfarin. An oral heparin would avoid the inconvenience of subcutaneous injections and adverse events associated with warfarin. A mild chitosan/PEG/calcium alginate microencapsulation process, as applied to encapsulation of biological macromolecules such as heparin and LMW Hep was investigated. Heparin and LMW Hep entrapped alginate beads were further surface/enteric coated with chitosan and cellulose acetate phthalate (CAP) via carbodiimide (EDC) functionalities. It was observed that approximately 70% of the content is being released into Tris-HCl buffer, pH 7.4 within the initial 6 hours and no significant release of LMW Hep was observed from enteric coated microspheres (12%) during treatment with 0.1 M HCl, pH 1.0 for 4 hours. But acid treated capsules had released almost all the entrapped LMW Hep into Tris-HCl, pH 7.4 media within 6 hours. From scanning electron microscopic and swelling studies, it appeared that the surface coatings (via chitosan and CAP) had modified the alginate microspheres and subsequently the drug release. The released heparin and LMW Hep had shown their anticoagulant functions. These results established the feasibility of modifying the formulation in order to obtain the desired controlled release of bioactive agent (LMW Hep), for a convenient pH dependent delivery system.

A case of chylothorax following innominate vein thrombosis, which developed as a late complication of transvenous pacemaker implantation, is discussed. A 78-year-old man presented with a refractory left-sided pleural effusion, which turned out to be chylothorax. He had undergone a transvenous pacemaker implantation 6 years earlier for sick sinus syndrome. The aetiological workup showed occlusion of the innominate vein as the cause for the chylothorax. The chylothorax resolved following pleurodesis with talc slurry, and the innominate vein was recanalized by angioplasty. To our knowledge this is the first report of a case of this nature.

Aims There is increasing evidence of the role direction-dependent conduction plays in the arrhythmogenic interaction between ectopic triggers and abnormal atrial substrates. We thus sought to characterize direction-dependent conduction in chronically stretched atria. Methods and results Twenty-four patients with chronic atrial stretch due to mitral stenosis and 24 reference patients with left-sided accessory pathways were studied. Multipolar catheters placed at the lateral right atrium, crista terminalis, and coronary sinus (CS) characterized direction-dependent conduction along linear catheters and across the crista terminalis. Bi-atrial electroanatomic maps were created in both sinus rhythm and an alternative wavefront direction by pacing from the distal CS. This allowed an assessment of conduction velocities, electrogram, and voltage characteristics during wavefronts propagating in different directions. While differing wavefront directions caused changes in both chronic atrial stretch and reference patients ( P < 0.001 for all), these direction-dependent changes were greater in chronic atrial stretch compared with reference patients, who exhibited greater slowing in conduction velocities ( P = 0.09), prolongation of bi-atrial activation time ( P = 0.04), increase in number ( P < 0.001) and length ( P < 0.001) of lines of conduction block, increase in fractionated electrograms ( P < 0.001), and decrease in voltage ( P = 0.08) during left-to-right compared with right-to-left atrial activation. These direction-dependent changes were associated with a greater propensity for chronically stretched atria to develop atrial fibrillation ( P = 0.02). Conclusions Atrial remodelling in chronic atrial stretch exacerbates physiological direction-dependent conduction characteristics. Our data suggest that the greater direction-dependent conduction seen in patients with chronic atrial stretch may promote arrhythmogenesis due to ectopic triggers from the left atrium.

The principal cause of the clinical failure of bioprosthetic heart valves fabricated from glutaraldehyde-pretreated bovine pericardial valves is calcification. The present investigation describes the mineralization of glutaraldehyde-treated bovine pericardium (GBP), in an extra-circulatory environment and the possible methods of prevention via metal ions. Calcification was examined on GBP incubated in metastable solutions of calcium phosphate and the role of certain anesthetic drugs, ferric ions and magnesium ions in the media was evaluated. It seems that the addition of ethyl alcohol, pentothal and xylocaine in the calcium phosphate solutions, variably inhibited the GBP calcification. The metals like Fe3+ ions and Mg2+ ions and their combinations also substantially reduced the GBP mineralization. It is assumed that ferric ions may slow down or retard the calcification process by delaying the proper formation of hydroxyapatite while magnesium ions disrupt the growth of these crystals by replacing Ca2+. Hence, it is conceivable that a combination therapy-via local delivery of low levels of ferric ions and magnesium ions-may prevent the GBP-associated calcification. Further, a very low daily intake of alcohol appears to be beneficial to reduce the profile of calcium deposition at tissue interfaces.

Hantaviruses cause hemorrhagic fever with renal syndrome in Europe and Asia. There are about 20 documented hantavirus species and newer species are being described worldwide, especially in non-rodent reservoirs, i.e shrews. Focus reduction neutralization test is the classical serotyping technique for hantavirus. However, this study employs a previously established serotyping ELISA, to retrospectively analyze known hantavirus IgG reactive samples for infecting serotypes. The result suggests presence of Thailand virus- like and Hantaan virus -like strains in India.

The emerging viral diseases haemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS) are a cause of global concern as they are increasingly reported from newer regions of the world. The hantavirus species causing HFRS include Hantaan virus, Seoul virus, Puumala virus, and Dobrava-Belgrade virus while Sin Nombre virus was responsible for the 1993 outbreak of HCPS in the Four Corners Region of the US. Humans are accidental hosts and get infected by aerosols generated from contaminated urine, feces and saliva of infected rodents. Rodents are the natural hosts of these viruses and develop persistent infection. Human to human infections are rare and the evolution of the virus depends largely on that of the rodent host. The first hantavirus isolate to be cultured, Thottapalayam virus, is the only indigenous isolate from India, isolated from an insectivore in 1964 in Vellore, South India. Research on hantaviruses in India has been slow but steady since 2005. Serological investigation of patients with pyrexic illness revealed presence of anti-hantavirus IgM antibodies in 14.7% of them. The seropositivity of hantavirus infections in the general population is about 4% and people who live and work in close proximity with rodents have a greater risk of acquiring hantavirus infections. Molecular and serological evidence of hantavirus infections in rodents and man has also been documented in this country. The present review on hantaviruses is to increase awareness of these emerging pathogens and the threats they pose to the public health system.

We present two cases of segmental arterial mediolysis, which can present with dissecting aneurysms or thrombosis of the visceral branches of the abdominal aorta. Segmental arterial mediolysis (SAM) causes ischemic bowel disease and has characteristic CT and angiographic features.

Two young female patients with Takayasu arteritis presented with symptomatic long-segment abdominal aortic stenosis in the vicinity of previously deployed celiac and renal artery stents that projected markedly into the narrowed aortic lumen. Crushing or distortion of the visceral artery stents during aortic angioplasty was avoided by performing simultaneous or alternating balloon dilatations in the aorta and in the visceral artery stents. Consequently, the visceral artery stents remained patent and shortened longitudinally, allowing unhindered deployment of Wallstents in the adjacent aorta and abolition of a pressure gradient across the aortic lesions. Access to side branches covered by the Wallstent was obtained without difficulty, enabling the performance of balloon dilatation in multiple side branches and ostial stent deployment in a renal artery. These techniques could increase the scope of endovascular therapy in the treatment of patients with Takayasu arteritis.

Radiation doses to patients during cardiological procedures are of concern in the present day scenario. This study was intended to audit the radiation dose imparted to patients during the balloon mitral valvuloplasty (BMV) procedure. Thirty seven patients who underwent the BMV procedure performed using two dedicated cardiovascular machines were included in the study. The radiation doses imparted to patients were measured using a dose area product (DAP) meter. The mean DAP value for patients who underwent the BMV procedure from one machine was 19.16 Gy cm(2) and from the other was 21.19 Gy cm(2). Optimisation of exposure parameters and radiation doses was possible for one machine with the use of appropriate copper filters and optimised exposure parameters, and the mean DAP value after optimisation was 9.36 Gy cm(2).

For patients with renal artery stenosis, percutaneous transluminal angioplasty is generally the treatment of choice. This report describes the case of an elderly lady with type III aortoarteritis whose right renal artery was successfully recalized and stented. There was satisfactory improvement in renal function and blood pressure post-procedure, and at one-month follow-up.

This study was undertaken to determine the prevalence of coronary artery disease in patients with rheumatic heart disease undergoing valve surgery.Consecutive patients with rheumatic heart disease (n=376) who were above the age of 40 years, and scheduled for valve surgery underwent diagnostic coronary angiogram to delineate coronary arteries. The patients were divided into three groups based on valve involvement (mitral valve, aortic valve, and combined aortic and mitral valve). Significant coronary artery disease was considered to be present if one or more coronaries showed 50% or more luminal stenosis. There were 287 (76.3%) males and 89 (23.7%) females. The mean age of the study population was 51.2+/-8.2 years. Eighty-nine (23.8%) patients had typical chest pain, 116 (30.6%) patients had atypical chest pain and 171 (45.5%) patients had no chest pain. Hypertension was noted in 88 (23.4%) patients, 65 (17.3%) patients had diabetes, 98 (26.1%) patients were smoker, and 66 (17.6%) patients had dyslipidemia, and 15 (4.0%) patients gave past history of myocardial infarction. Of the total 376 patients, 46 (12.2%) patients were found to have significant coronary artery disease. In patients with mitral vale disease the prevalence was 13.5% (13/96), while it was 15.3% (19/124) in patients with aortic valve disease and 9% (14/156) in those with combined mitral and aortic valve disease.Our results suggest that the overall prevalence of coronary artery disease in a group of patients with rheumatic heart disease undergoing valve surgery in the current era is 12.2%. This prevalence is much lower than the figures reported earlier in the Western literature.

Cardiac resynchronization therapy has emerged as a new therapeutic modality for patients with congestive cardiac failure and associated intraventricular conduction delay. The purpose of this study was to find out what proportion of Indian patients with congestive heart failure may be candidates for cardiac resynchronization therapy based on electrocardiographic characteristics.One hundred twenty-one consecutive patients with congestive cardiac failure due to various etiologies whose left ventricular ejection fraction was less than 40% were included in the study. Standard 12-lead electrocardiogram was recorded in all the patients, and various parameters (rhythm, conduction, QRS axis, chamber enlargement, chamber hypertrophy, and the presence of Q waves) were analyzed. The study population comprised 82 male (67.8%) and 39 female (32.2%) patients with a mean age of 53 +/- 13 years. Thirty-nine patients (32.2%) had NYHA class I-II symptoms, and 82 (67.8%) had NYHA class III-IV symptoms. The mean QRS duration was 111 +/- 27 ms. Bundle branch block was seen in 43 patients (35.5%), of whom 30 (24.8%) had left bundle branch block, and 13 (10.7%) had right bundle branch block. Of the 30 patients who had left bundle branch block, 19 (15.7%) had a QRS duration of between 120 and 149 ms, and 11 (9%) had a QRS durationor = 150 ms. In the latter group, 7 patients (5.8%) were in NYHA classes III and IV. As the clinical severity of heart failure increased, the mean QRS duration also increased, but this increment was not statistically significant.Based on our data, it can be estimated that of the patients with heart failure who attend a tertiary care center, 2 5% of patients present with left bundle branch block. If we use the criteria for NYHA class III and IV congestive cardiac failure with QRS duration ofor = 150 ms in patients with left bundle branch block, 6% of patients are likely to need cardiac resynchronization therapy.

A technique is described to encapsulate activated charcoal for hemoperfusion to be used in an artificial liver support. Activated charcoal was encapsulated within chitosan-PEG matrix and subsequently surface modified with PGE1 or heparin (hep-AC-PEGCB) via the glutaraldehyde functionalities. This novel matrix was used as the supports for perfusion of endotoxin, under a flow rate of 30 ml/mt. Endotoxin adsorption was quantitatively measured by the method of Limulus Amebocyte lysate test. It seems, the hep-AC-PEGCB may be a good adsorbent system for the removal of toxic endotoxin, and the system may be useful for detoxification of blood. The hep-AC-PEGCB matrix had improved biocompatibility as demonstrated from their hemolytic potential and charcoal release. However, further studies are needed to determine their behaviour under clinical conditions.

A bioartificial pancreas, a medical device entrapping islets of Langerhans (islets) in an immunoisolative membrane, has been regarded as one of the most promising approaches to treat insulin-dependent diabetic patients. In this study, various modifications of alginate-chitosan microcapsules were made such as the inclusion of polyethylene glycol (PEG) and the use of crosslinkers such as carbodiimide (EDC) and glutaraldehyde (GA) in the core and onto the microcapsule membrane surface. A characterization of the modified microcapsules in terms of mechanical stability and albumin diffusion as well as their surface properties using SEM was performed. A mild GA treatment greatly enhanced the mechanical stability of the microcapsules, and this treatment did not affect the coating process of chitosan or PEG. The biological response to such microcapsules was evaluated by microencapsulation of red blood cells (RBC) and subsequent observation of their hemoglobin release. The encapsulated RBC in the PEG-GA coated microcapsules were found to be less hemolytic and had improved stability and biocompatibility. The results suggest the possibility of developing biological assist organs by microencapsulation of mammalian cells such as islets or liver cells in immunoisolative microcapsules in the near future.

Platelet attachment and spreading were monitored on glass and various protein coated glass, under shear with washed platelets, platelet rich plasma (PRP) and whole blood, using fluorescence Optimas imaging system and software. Results showed that the platelet adhesion and spreading were sensitive to the nature of precoated proteins and the type of medium used for introducing platelet suspension for the study. In general, the cell adhesion and spreading were higher with fibrinogen (Fg), fibronectin (Fn), von Willebrand Factor (vWF), and collagen precoated surfaces. In the presence of albumin on the surface, however, platelets could not attach and spread fully when using washed cells. But, the surface attachment and spreading of the cells were higher on albumin substrates on exposure to PRP or whole blood. This may be due to the replacement of precoated albumin by other plasma proteins, like Fg to facilitate the platelet-surface attachment. The composition of this layer determines the extent of platelet activation and the adhesive strength between platelets and polymer surface. These results indicate that multiple adhesion receptors can mediate platelet adhesion and spread to matrix proteins immobilized on surfaces. Further, these studies combined with some of our earlier observations and suggestions propose the need for developing in vitro tests that resemble in vivo conditions.

Current epidemiologic reports claim an important role for triglycerides in coronary artery disease (CAD). By cross-sectional data analysis, the role of triglycerides was assessed in 1726 consecutive patients investigated for chest pain, 1119 with CAD and 607 with normal coronaries. Besides study of male and female patients as separate groups, the males were divided into age groups of below 40 years, 41 to 50 years, 51 to 60 years and over 61 years. The female patients were divided into those below 50 years and over 51 years because of smaller numbers. Using the mean value for cholesterol, triglyceride, HDL cholesterol, LDL cholesterol and body mass index for normals as the demarcation line, logistic regression analysis was carried out to study their association in the patients with CAD and normals. Results showed that while the odds ratio for total cholesterol were higher for the younger age groups, the odds ratio for triglycerides were consistently higher for the groups over 51 years both male and female. It is speculated that there may be a difference in the relative importance of lipid fractions with reference to age in the development of atherosclerotic plaque with cholesterol playing a more important role in younger people and triglycerides being equally or more important in older people, on the basis of metabolic handling of lipid fractions.

Biomaterial associated calcification is the principal cause of the clinical failure of bioprosthetic implants. The present investigation describes the mineralization of polymeric substrate in an extracirculatory environment and the possible methods of prevention. Calcification was examined on various polyurethane films (and bioprosthetic tissue) incubated in metastable solutions of calcium phosphate and the role of polymer casting and precipitation was evaluated. The formulation and the in vitro efficacy of prolonged controlled-release chitosan matrices, containing the novel anticalcification agents, such as Fe+++ or protamine sulfate (PS), were also attempted. The in vitro release profiles of PS from chitosan beads was performed in a rotating shaker (100 rpm) in 0.1 M phosphate buffer (pH 7.4) and was monitored spectrophotometrically. The amount and percentage of drug release were much higher initially, which was controlled with the incorporation of egg phosphatidyl choline (EPC). The PS loaded chitosan beads (coincubated in calcium phosphate solution with the calcifiable polyurethane films) significantly inhibited biomaterial calcification (about 40–50% inhibition). Surface modification of polyurethanes with Fe+++ or PS also inhibited the calcification profile of the material. These findings suggest the possibility of a combination therapy for prevention of biomaterial associated calcification via surface modifications in conjunction with long-term controlled release of the anticalcifying drugs. © 1994 John Wiley & Sons, Inc.

A technique is described to encapsulate activated charcoal for haemoperfusion to be used in an artificial liver support. Activated charcoal was encapsulated within chitosan matrix (ACCB) in different concentrations, and was used as the supports for perfusion of a mixture of solutes, having molecular weight ranges from 60 to 69,000; under a flow rate of 8 ml/min. It seems the ACCB may be a good adsorbent system for the removal of toxic uric acid, creatinine, bilirubin, etc., from solutions; while larger molecules such as albumin are adsorbed less. The encapsulated charcoal did not leach out from the matrix during perfusion, and the system may be useful for detoxification of blood. The haemolytic potential of ACCB has been compatible with polystyrene control tubes. However, further studies are needed to determine their behaviour under clinical conditions.

Hyperbilirubinemia generally relates to an elevated bilirubin level in the blood and is usually an indication of a disease of the blood, liver, or biliary tract. Hemoperfusion using synthetic resins as sorbents has been one of the ways to reduce bilirubin. In this study, chitosan, a natural polysaccharide having structural characteristics similar to glycosaminoglycans and which is nontoxic and biocompatible, has been used for bilirubin binding. Several layers of poly-L-lysine have been coated covalently onto chitosan beads, using N2 plasma and carbodiimide treatments. Such surface-modified chitosan beads exhibited high binding affinities for bilirubin (1.13 +/- 0.18 mg/g beads) in aqueous phosphate buffer solutions at 4 degrees C in relation to activated charcoal (0.74 +/- 0.2 mg/g). The polylysine-coated resins have been reported to have an improved binding affinity for bilirubin over cholestyramine. It seems that the surface-immobilized polylysine has an increased bilirubin binding affinity and is highly stable. The binding capacity is proportional to the amount of polylysine bonded to the chitosan beads. The hemolytic potential of all modified beads is compatible with polystyrene control tubes. Studies were also performed against albumin as proof of specificity toward bilirubin binding. The albumin-coated beads have shown the highest blood compatibility and selectivity over the other modified beads. However, it appears that polylysine-modified chitosan may be an excellent sorbent system for hemoperfusion due to its high binding affinity, capacity, and blood compatibility. Further studies are needed to determine its behavior under clinical conditions.

Chitosan [a (1----4) 2-amino-2-deoxy-beta-D-Glucan] is a unique polysaccharide derived from chitin. Several attempts have been made to use this biopolymer in biomedical field. The use of this material in the development of hemodialysis membranes, artificial skin, drug targetting and other applications are discussed. It appears, this novel biomolecule, biodegradable, and biocompatible, find applications in substituting or regenerating the blood/tissue interfaces. This polysaccharide having structural characteristics similar to glycosaminoglycans, seems to mimic their functional behaviour.

Natural rubber with C = C bonds had been modified by reaction with chlorosulfonyl isocyanate (CSI) and 70% of the products were obtained, which yielded poly-electrolyte on treatment with NaOH, having sulfamate and carboxylate groups. The polyelectrolyte showed anticoagulant activity. This might be due to the presence of both sulfamate and carboxylate groups arranged in a steric manner in the molecule as that of Heparin. Surface energy parameters, platelet adhesion and plasma recalcification time were investigated. Possible comparison with heparin had been demonstrated.

When a synthetic material is introduced into blood, plasma proteins are rapidly adsorbed on to its surface, followed by the attachment of formed elements of blood, leading to thrombus formation. Previous research reported that vitamin C (L-ascorbic acid) prolongs the clotting time due to the formation of vitamin C-calcium complexes, which reduce the availability of Ca2+ ions for the clotting mechanism in in vitro conditions. Contact angle and platelet adhesion studies have indicated that vitamin C modifies the surface-protein interaction and surface-platelet binding at the interface. In this paper an increased thickness of protein layer deposited on the polycarbonate substrate has been observed in the presence of vitamin C (approximately 50 A) using ellipsometric measurements. Further polyacrylamide gel electrophoresis (PAG) and infrared attenuated total reflection spectroscopy (IR-ATR) techniques have provided a better understanding of the interfacial phenomena. It seems, that the adsorption of albumin is increased, relatively, in the presence of vitamin C, when compared with that of fibrinogen and gamma-globulin from an equal amount of protein mixture.

Plasma glow technique has created much interest in the field of surface modification of polymers due to its versatility of generating active polar groups on the surface without affecting the bulk properties. Here an attempt is made to inter-relate the surface properties and platelet adhesion on various polymeric substrates due to plasma treatments. Initially, a critical review of the process and development of thrombosis upon contact of an artificial surface with blood, has been provided, which has been extended with the need for surface modifications to improve their blood compatibility and the versatility of plasma treatments for such modifications have been emphasized. Phospholipids like phosphoryl choline, phosphatidyl choline and phosphoryl ethanolamine were attached to Angioflex surface by plasma glow. The role of such modified substrates to interact with platelets were investigated using Tyrode washed calf platelets. It seems, glow discharge modified phosphoryl choline bilayers dramatically inhibited the platelet-surface binding, which may be due to their biochemical resemblance with thromboresistant surfaces of human blood cells. Further, the behaviour of all phospholipids towards blood-polymer interaction is not similar and may change depending on the nature of their functional groups, net charge of the phospholipid adsorbed surface and their interaction with platelets and its activation. It is possible to chemically immobilize lipid bilayers on standard polymers, using plasma glow, to improve their biological performance; by suitably selecting the phospholipid combinations.

The development of injectable microspheres for anticancer drug delivery into the brain is a major challenge. The possibility of entrapping 5-fluorouracil (5-FU) in chitosan coated monodisperse biodegradable microspheres with a mean diameter of 10-25 um was demonstrated. An emulsion of 5-FU (in water) and polylactic acid (PLA) dissolved in acetone-dichloromethane mixture was poured into an aqueous solution of chitosan (or poly-vinyl alcohol) with stirring using a high-speed homogenizer, for the formation of microspheres. 5-FU recovery in microspheres ranged from 44-66% depending on the polymer and emulsification systems used for the preparation. Scanning electron microscopy revealed that the chitosan coated microspheres had less surface micropores compared to PVA based preparations. The drug release behaviour from microspheres suspended in phosphate buffered saline exhibited a biphasic pattern. The amount of drug release was much higher initially (approximately 25%), followed by a constant slow release profile for a 30 days period of study. This chitosan coated PLA/PLGA microsphere formulation may have potential for the targeted delivery of 5-FU to treat cerebral tumours.