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Study of atrial arrhythmias after surgical or device closure of atrial septal defect
No full textAtrial septal defects(ASD) are common cardiac malformations accounting for 10% of
congenital heart defects at birth(1). The incidence after the advent of echocardiography is
estimated to be around 100 per 100 000 livebirths(2). Patients with atrial septal defects on
long term follow up are noted to develop pulmonary hypertension, right heart failure,
paradoxical embolism, reversal of shunt with development of cyanosis (Eisenmenger
syndrome) and atrial arrhythmias. Patients with ASDs have good prognosis with 0.6 to
0.7 % mortality rate per year in the first two decades of life and thereafter with every
passing decade it rises from 2.7% to 4.5% to 5.4% to 7.5% per year(1). Atrial
tachyarrhythmias like atrial fibrillation(AF) and atrial flutter are well documented in
adult patients with atrial septal defects which may result in significant comorbidity and
occasionally death(3,4). The geometrical and electrical remodelling of the right atrial and
right ventricular chambers due to left to right shunt is postulated to contribute to the
development of atrial tachyarrhythmias(5). Surgical closure of ASD was the initial
treatment option available. Studies have shown new onset atrial arrhythmias after ASD
surgical closure. Incidence of atrial arrhythmias was related to the age at which patients
undergo surgical ASD closure. Ghosh et al observed a lower incidence of preoperative
AF (23.5% vs 43.6%, p < 0.05) among patients 35-50 years old than among patients older
than 50 years and a lower incidence of new AF (7.8% vs 34%, p < 0.05) in the former
than the latter group(6). In another study new onset atrial flutter or atrial fibrillation was
more likely to have developed at follow up in patients older than 40 years at the time of
surgery than I those who were 40 or younger(5 of 67 vs. o of 106, p=0.008). This study
also showed almost 60% of patients persisted to have atrial flutter and fibrillation post
surgical ASD closure(7). The incidence of atrial tachyarrhythmias is lower if ASD is
closed at a younger age but not eliminated. Patients younger than 15 years of age also had
around 6% incidence of supraventricular arrhythmias(8). The etiology of atrial 3
arrhythmias post surgical repair is not completely understood. The Indexed RA area
decreases over time after surgical ASD closure but still remains increased in comparison
to that in control subjects and the decrease in RA area is inversely proportional to the
patient’s age at the time of the ASD closure(9). Percutaneous device closure of ASD is
now an attractive and established method of ASD treatment. Since surgical scarring of
atrium is avoided in transcatheter closure of ASD, atrial arrhythmias are expected to have
a lower incidence in patients undergoing transcatheter ASD closure. However studies
have shown incidence of new onset atrial arrhythmias after device closure as well and the
incidence increases with age. In a study by Vajapey et al, new onset atrial arrhythmias
was 8.5%, 17.1% and 32.5% respectively for age 18-40 years and 41-60 years and above
60 years of age at the time of closure(10). However, there is paucity of studies comparing
the incidence of atrial arrhythmia in surgical versus transcatheter atrial septal defect and a
difference in nature of atrial arrhythmias is not well established. Our study also attempts
in understanding whether a difference exists in new onset atrial arrhythmias between
surgical and ASD device closure patients in long term. Our study will also help the
clinician to understand and anticipate arrhythmic complications on long term follow up of
post ASD closure patients and help clinicians in prompt detection and appropriate
management of various arrhythmias
Immediate and intermediate term outcome of arterial switch operation in transposition of great arteries
No full textBackground: Dextro Transposition of Great Arteries (D TGA) accounts for 5 – 7% of all
congenital heart defects (CHD) with a prevalence of 0. 2 per 1000 live births and male
predominance. The arterial switch operation (ASO) has replaced the old atrial switch
procedures developed by Senning and Mustard in the management of d-transposition of
the great arteries (D-TGA) for the last 40 years after Jatene performed the first successful
ASO in 1975. Since then survival rates have improved over years with refinement of
surgical techniques and improved medical management. Currently, most treated patients
live to adulthood, with a 20-year survival of about 90% as reported from various
international centres. Operative mortality for simple TGA is reported in the range of 2-
7%, compared to 15% as found in earlier studies. Risk factors for operative mortality
includes the presence of a ventricular septal defect, older age at repair, coexisting
anomalies, and anomalous coronary patterns.
Aims and Objectives: Current study is aimed at finding out risk factors of early
mortality and intermediate term outcomes of children undergoing ASO. Indian data
regarding factors affecting mortality rates and follow up data are scarce, and hence this
study.
Materials and Methods: It was a retrospective observational study with cross sectional
follow up which included patients with simple TGA with or without VSD who underwent
Arterial switch operation between 1 st January 2008 to 30 June 2018 in SCTIMST.
Bsaseline demographic data, peri operative parameters were collected. In the immediate
post operative period arrhythmias, ventricular dysfunction, Coronary flow and deaths,
and in the intermediate term neo Aortic incompetence, Neo pulmonary stenosis ,
ventricular dysfunction/Heart failure, arrhythmia, and the incidence of re intervention (s)
were looked into. Results: Most patients were male babies. BAS was done in 149 out of 168 children (88.
69%). Regressed left ventricle was found in 17 children (10. 24%). Mean age at surgery
for patients with normal LV function was 26. 13+/- 21. 76 days whereas in patients with
regressed LV it was 72. 64 +/-101. 71 days. 22 patients underwent ASO +VSD closure, 2
underwent ASD closure and 1 patient underwent PDA ligation. 34 patients underwent
ASO after 1 month of life,out of which 5 patients died in the immediate post operative
period Among patients who were surviving 37. 5 % were free from neo aortic
regurgitation, and 12. 5 % free from neo pulmonary regurgitation. Mild neo AR was seen
in 34. 52% and more than mild in 16%. The most common artery pattern was 1LCX2R in
77. 38%. Early arrhythmia occurred in 8 patients (4. 76%). There were probable 5 SCD
(likely arrhythmic events). Early mortality rate was 7. 1 % and the overall mortality 10.
68 %. Sepsis was seen in 10 out of 12 patients who died in the early post operative
period. On follow up 14 patients had developed supravalvar pulmonary stenosis. 6
children had only mild PS, 8 had severe supravalvar PS. Multivariate regression analysis
revealed that ionotrope duration and Left ventricular dysfunction were independently
associated with early mortality. Coronary pattern was not associated with mortality.
Actuarial survival was 89. 29% at median follow up of 43. 63 months. Freedom from re
interventions was 91. 82 % at the end of 5 years.
Conclusions: Coronary anatomy, Birth weight did not affect the outcome of our cohort
of 168 children who underwent ASO at our centre. Sepsis was the commonest cause of
in – hospital death in 10 out of 12 children. Predictors of mortality were left ventricular
function and ionotrope duration in multivariate analysi
Prevalence of unexpected red cell antibodies in healthy donor population in a tertiary care center in south kerala
No full textNaturally occurring anti-A and anti-B are the only red cell antibodies that
are commonly found in human serum or plasma. All other antibodies are
called “unexpected red cell antibodies [1]. There are two types of
unexpected red cell antibodies: alloantibodies and auto-antibodies.
Alloimmunization occurs because of red cells antigenic differences
between donor and recipient in previous transfusions or between mother
and fetus. Auto-antibodies are those produced against one’s own antigens.
Immune humoral response in the presence of autoantibodies against
intracellular antigens characteristically occurs in a majority of connective
tissue diseases namely systemic lupus erythematous, systemic sclerosis,
Sjögren syndrome, mixed connective tissue disease, polymyositis, and
dermatomyositis [2]. Presence of these antibodies, alone or in combination,
makes difficulties with compatibility testing, thereby delaying in issue of a
compatible blood unit or may reduce post transfusion RBC life span [3].
The compatibility test comprises ABO/Rh determination, antibody screen
and cross-match. Type & cross-match technique/Immediate spin cross
match is routinely practised now which only detects ABO
incompatibility between donor RBCs and recipient serum/plasma. Type &
screen method is performed only when the recipient has unexpected
alloantibodies to detect additional RBC incompatibility [4]. Because of the
presence of auto-antibodies, all crossmatches become incompatible.
Studies conducted based on these unexpected antibodies have largely
concentrated on multiply transfused patient populations or antenatal
women. Alloimmunization in these groups has a reported incidence up to
60 percent, with an up to fourfold increased risk of multiple antibodies
compared to the risk of single antibodies [5]. However, such studies related
to healthy donor population are not done extensively. The incidence of RBC
alloimmunization depends on the demography and characteristics of the population being studied. The specificity, Ig class, thermal range and
concentration of the antibody can predict its clinical significance as well as
patient’s individual immune response is also significant factors. The
balance between sensitivity and specificity can be influenced by the
methods and technologies selected. It is not possible to detect all potentially
clinically significant antibodies, or to avoid detecting all clinically
insignificant antibodies [6].
The Direct Antiglobulin test (DAT) is a simple test used to determine if red
cells have been coated in vivo with immunoglobulin (Ig), complement or
both. It is used primarily for the investigation of hemolytic transfusion
reactions, haemolytic disease of the fetus and newborn (HDFN),
autoimmune hemolytic anemia (AIHA), and drug-induced immune
hemolysis. An indirect antiglobulin test (IAT) is used to detect and identify
unexpected antibodies in the serum of blood donors, prospective
transfusion recipients, and prenatal patients [7]. IAT detect in
vitro antibody-antigen reactions and detect very low concentrations of
antibodies present in an individual’s plasma/serum.
When unexpected antibodies are present, as indicated by positive screening
tests, they must be identified. At a minimum, this involves testing the
patient’s serum against a panel of fully phenotyped reagent red cell samples
as well as the patient’s own cells [6]. A recent study suggests that a positive
DAT result in a healthy blood donor may be a marker of risk of future
development of malignancy [8]. All these point towards the need of Type
& Screening system to be followed routinely in transfusion practices rather
than Type & Matching system. Antibody screening is mandatory as laid
down by Drug and Cosmetic Act 1940 and Directorate General of Health
Services (DGHS) guidelines. Hence through this thesis work, we are implementing routine antibody screening along with DAT testing in every
donated units in our Institute.
Our donor pool consists of 100% voluntary regular donors who are
considered to be absolutely safe and almost free of any infections and
highly motivated. This study also helps to find the prevalence of irregular
antibodies in such healthy donors there by aiding best transfusion practices
to be followed in the institution since there is scarce data available on
prevalence and type of irregular antibodies in Indian donor population
Cytoskeletal synchronization of CHO cells with polymer functionalized fullerene C60
No full textRecent developments in the field of fullerene C60 and its derivatives suggest its suitability in a wide range of applications ranging from photovoltaic instruments, development of solar based cells, cosmetics to enzyme inhibition treatment, and so on. These innovative applications raised possibilities of intentional or oblivious human-particle contact leading to possible deleterious effects on human health. The current study deals with the interaction of dextran functionalized fullerene C60 (Dex-C60) on Chinese Hamster Ovary cells. The results showed that the cell viability was not affected by Dex-C60 treatment even at higher concentrations. Treatment of Dex-C60 did not affect mitochondrial membrane potential and the integrity of lysosomal and cytoskeletal membrane. DNA ladder assay and nuclear staining showed that the DNA remains intact, and no fragmentation or nuclear condensation was visible. From flow cytometry analysis, the viable population of treated cells was seemed to be remaining similar to that of untreated cells. Hence, from the current result, it is concluded that Dex-C60 can be a potential candidate for various biomedical applications
Prospective observational study of outcomes of different transcranial approaches for craniopharyngiomas
No full textCraniopharyngioma:
“One would expect these congenital epithelial tumors to be capable of
enucleation like Dermoid cysts elsewhere in the body, but they so definitely adhere to
the adjacent structures neighboring on their place of origin, it is rarely possible to
shell them out of their bed without the production of serious secondary symptoms. To
be sure, one may occasionally succeed in stripping out a thin-walled cyst, and
examples of this have been reported, but when the tumor is partly solidified, and
calcareous, sad experience warns the surgeon to leave it pretty much alone.” Harvey
Cushing, 1932. (1)
“Though this tumor is still an ominous disease, it seems fair to say, that the
outlook has improved considerably.” (2)
Craniopharyngiomas are rare CNS tumors defined by WHO as benign, partly
cystic epithelial tumor of the sellar region presumably derived from Rathke’s pouch
epithelium. While it is benign in nature, the adhesion to surrounding structures may
result in damage to sellar and parasellar tissues during surgery and hence it is called
“Benign Tumor in a malignant location.” (3)
However due to introduction of hormonal therapy has allowed optimal
correction endocrinal deficiency, and improvement in radiation and microsurgical
techniques have improved survival enormously, it is the quality of survival that has
become real challenges.
The results of the published studies of neuropsychological outcome in children
are often conflicting and controversial. However surgical approaches of
craniopharyngioma need to be addressed with regards to neuropsychological outcome.
This study serves the above mentioned purpose
A clinical study on the utility of muscle biopsy in patients with suspected myopathy
No full textMyopathy is one of the common disorders in patients attending neuromuscular clinic.
Systematic approach comprising a comprehensive clinical history, thorough neurological and
systemic examination, nerve conduction studies, EMG and relevant biochemical tests should
be undertaken in all cases. Muscle biopsy is one of the most frequently used diagnostic
procedures in the evaluation of inherited and acquired myopathies. The yield of muscle biopsy
result is dependent on number of factors, including appropriate selection of patients for biopsy,
expertise of the laboratory, and techniques used in the analysis.
The history of muscle biopsy dates back to 1860 when Duchenne first performed a biopsy on
a patient with symptoms of myopathy. Introduction of enzyme histochemical methods by
Victor Dubowitz in 1970 revolutionised the role of muscle biopsy in the diagnosis of various
primary and secondary muscle diseases(7). Diagnosis of various subtypes of dystrophies was
further made easy with beginning of immunohistochemical methods in 1980s However, there
are few modern reports documenting the diagnostic yield and clinical utility of open muscle
biopsy.(1-5) Clinicians usually rely on personal experience to develop their own criteria for
performing muscle biopsy. This may explain the variable diagnostic outcome of muscle biopsy
found in previous cohorts which ranged from 13.2% to 59.9%.(8,9).
In most of the proximal myopathies and generalised/systemic diseases; vastus lateralis is the
standard muscle biopsied by international consensus. (6) The other muscles that are good
choices for biopsy are biceps and gastrocnemius. However, many forms of hereditary muscle
disorders can now be diagnosed with molecular genetic testing, thereby eliminating the need
for performing a muscle biopsy in every patient.
In this study, we evaluate the clinical utility of muscle biopsy in patients with suspected
myopathy. The primary objective is to determine the diagnostic value of muscle biopsy, as
measured by the probability of specific myopathy and depending on the available pre procedure clinical and laboratory dat
Bioengineered mesenchymal cell sheets as an alternate to limbal stem cells for ocular surface reconstruction
No full textComparison of two anaesthetic regimens TIVA (Propofol-fentanyl) versus Inhalation (Sevoflurane-fentanyl) on perioperative haemodynamic, operating conditions and immediate postoperative outcomes in patients undergoing elective neurosurgical procedures involving brain tumors
No full textNeurosurgical procedures involving craniotomy and resection of brain tumors are
usually carried out under general anaesthesia. The goals of anaesthesia during
neurosurgical procedures are smooth induction, stable intra operative haemodynamics,
providing optimal surgical condition, adequate brain relaxation, smooth and rapid
recovery after end of surgery. (1,2) Ideal anesthetic agent for neurosurgery should reduce
cerebral metabolism, maintain cerebral blood flow, maintain flow metabolism coupling,
reduce intracranial pressure, maintain auto regulation, maintain cerebrovascular reactivity
to carbon dioxide, maintain hemodynamic stability, rapid onset and early recovery. (3)
Rapid recovery after end of surgery leads to early neurologic examination and early
detection of any complications with appropriate treatment for it reduces mortality and
morbidity. Anaesthetic agent used in neurosurgery can have significant effect on
neurological outcome. (4) The commonly used techniques for conduct of anaesthesia for
neurosurgical patients are either using inhalation or intravenous anaesthesia using total
intravenous anesthesia (TIVA).
Total intravenous anaesthesia is achieved using an intravenous hypnotic agent
administered along with opioid whereas the inhalational technique involves the use of
halogenated anesthetics along with opioid. Drugs with rapid onset and offset like propofol
and remifentanil are most commonly used for TIVA. (5) As remifentanil is not available
in our hospital, we use routinely combination of propofol and fentanyl for TIVA. Among
the inhalational agents we routinely use Sevoflurane for neurosurgical procedures. Each
of the techniques has its own advantages and disadvantages.
Propofol can be used through manual infusion or target controlled infusion pump.
When propofol infusion is given in manual infusion pumps, pharmacokinetics of drug to
be utilized during infusion otherwise a fixed infusion rate may result in rising, declining
or stable concentration leading to underdosage or overdosage. For a stable plasma
concentration varying rate of infusion may be required. Availability of TCI pumps which
uses pharmacokinetics of the drug and microprocessor-based software helps to achieve
target plasma concentration and effect site concentration easily. (6) Using TCI pumps for
TIVA helps real time titration of effect site concentration and can be adjusted according to
processed EEG monitor for adequate depth of anesthesia. (7) TIVA has advantages of
rapid, smooth induction, reduced intracranial pressure, hemodynamic stability and less
incidence of PONV. (8) Propofol causes dose dependent reductions of cerebral metabolic rate and blood
flow so coupling of flow metabolism is maintained. It also causes reduction of intracranial
pressure. Carbon dioxide reactivity and autoregulation are maintained. (9,10) It has
property of rapid onset and is short acting, rapid recovery, reduces ICP, antiemetic and
anticonvulsant action which is beneficial in neurosurgery. (11,12) It has no analgesic
activity, so propofol combined with intravenous opioids for maintenance of anaesthesia.
All volatile anesthetics decreases cerebral metabolism in dose related manner. It
has also intrinsic vasodilator capacity due to direct action on vascular smooth muscle.
Final effect depends upon the balance between two effects. At 0.5 MAC, CMR
suppression predominates leading to decreased cerebral blood flow. At 1 MAC, CMR
suppression and vasodilatory effects are balanced so there is no net change. At more than
1 MAC vasodilatory effects are predominant leads to increase in blood flow and ICP.
Order of vasodilating potency is approximately halothane ≫ enflurane > desflurane ≈
isoflurane > sevoflurane. Sevoflurane is least vasoactive. Sevoflurane is fluorinated
methyl isopropyl ether. Vapor pressure is 160 mm of hg, so used in conventional
nonheated vaporizer. Blood gas partition coefficient is 0.69, so rapid induction and
recovery. At concentrations below 1.0 MAC has nearly no effect on cerebral blood
volume and intracranial pressure. (13,14,15) Cerebral metabolism is reduced to the same
extent when compared with equipotent concentrations of sevoflurane and propofol. (13)
Coupling between regional cerebral blood flow and metabolism is maintained with
sevoflurane and propofol. Autoregulation remains intact with 1.0 MAC sevoflurane (16).
Cerebrovascular autoregulation is maintained with 0.5 and 1.0 MAC sevoflurane,
although the fast dynamic component of autoregulation is slightly impaired with 1.0
MAC. (16,17,18) This suggests that concentrations below 1.0 MAC sevoflurane should be
suitable for neuroanesthesia. At high concentration when used for induction, seizure like
EEG pattern may be observed particularly in children having history of febrile
convulsion. (19) Concentration <1.5 MAC can be safely used in patients with Seizure
disorder. It has also neuroprotective effect due to inhibition of excitatory glutamate
sensitive NMDA receptor and activation of inhibitory GABA receptor. (20).
Though both the anesthetic regimens are being used for intracranial tumor surgery,
literature is inconclusive on which agent is better, due to low quality evidence. In a recent
Cochrane review, Prabhakar et al, have concluded that propofol and sevoflurane have equivalent effect on emergence from anaesthesia, propofol has lesser incidence of side
effects like PONV with no difference in brain relaxation scores between propofol and
sevoflurane group. (21) So, they could not draw any firm conclusions on the benefits of
any technique over another for use during brain tumour surgery.
One of the major drawbacks of the existing studies is that the authors have not
utilized the equivalent depth of anaesthesia for comparison as guided by processed
electroencephalogram (EEG). Hence the existing studies could not have a proper
comparison. It is important to use both the regimens to a common end point namely the
depth of anaesthesia. In the present study we have intended to compare the two regimens
using a targeted value of depth of anesthesia using Patient state Index (PSI) in patients
undergoing neurosurgical procedures on various perioperative indices
Improved Bioavailability of Curcumin in Gliadin-Protected Gold Quantum Cluster for Targeted Delivery
No full textThis study deals with the synthesis of a gliadin-stabilized gold quantum cluster (AuQC) for the encapsulation of curcumin (CUR) and its targeted delivery to the cancer cell. CUR is an anticancer drug containing a hydrophobic polyphenol derived from the rhizome of Curcuma longa. The utilization of CUR in cancer treatment is limited because of suboptimal pharmacokinetics and poor bioavailability at the tumor site. In order to improve the bioavailability of CUR, we have encapsulated it into AuQCs stabilized by a proline-rich protein gliadin because proline-rich protein has the ability to bind a hydrophobic drug CUR. The encapsulation of CUR into the hydrophobic cavity of the protein was confirmed by various spectroscopic techniques. Compared to CUR alone, the encapsulated CUR was stable against degradation and showed higher pH stability up to pH 8.5. The encapsulation efficiency of CUR in AuQCs was calculated as 98%, which was much higher than the other reported methods. In vitro drug release experiment exhibited a controlled and pH-dependent CUR release over a period of 60 h. The encapsulated CUR-QCs exhibited less toxicity in the normal cell line (L929) and high toxicity in breast cancer (MDA-MB239). Thus, it can be used as a potential material for anticancer therapy and bioimaging
