Pattern of reporting and practices for the management of traumatic brain injury: An overview of published literature from India.

BACKGROUND: Published literature regarding the demographics and mechanism of injury for traumatic brain injury (TBI) in India has not been analyzed in an organized sample. OBJECTIVES: The objective of this systematic review was to organize the published literature from India related to TBI and analyze it in a very specific sample to identify the specific patterns of injury and associated mortality. MATERIALS AND METHODS: A search strategy with specific inclusion criteria was performed in PubMed, Cochrane, Web of Science, and the World Health Organisation (WHO) Global Health Library. The process included an additional search within the indexed literature and the website-based population survey reports. RESULTS: Our review identified 72 studies from 300 potentially relevant articles based on the broad criteria that defined the demographics of the patients suffering from TBI and the details of trauma sustained, including the mechanism of injury as well as its diagnosis, management, and outcome. Changes in demographic patterns, the patterns of the body regions involved, the associated injuries, the clinical presentation, the follow-up status of patients suffering from TBI, who may or may not have shown clinical improvement, the overall outcome, as well as the mortality and disability status reported in the literature were analyzed. A high incidence of TBI in the productive population is of serious concern. Extremes of ages are more vulnerable to severe injury and a poor outcome. CONCLUSION: Quantitative analysis of injuries and outcomes of TBI victims shows a bigger health impact in the economically active population and in patients in the extremes of age groups.

Anatomy and morphology of giant aneurysms--angiographic study of 125 consecutive cases.

BACKGROUND: Giant intracranial aneurysms are rare and heterogeneous lesions with complex vascular anatomy. The aim of this retrospective study was to provide a comprehensive description of the anatomical features of giant aneurysms. METHODS: We identified 125 patients with 129 giant aneurysms (≥ 25 mm) who were treated between 1987 and 2007 at the Department of Neurosurgery of Helsinki University Central Hospital (HUCH). All the imaging studies and medical records were reviewed for relevant information. RESULTS: The distribution of the giant aneurysms among regions was as follows: internal carotid artery (ICA) 39%, middle cerebral artery (MCA) 32%, vertebrobasilar and posterior cerebral artery (VB-PCA) region 25%, and anterior cerebral artery (ACA) including the anterior communicating artery 5%. The cavernous ICA segment (n = 21, 16%) and the MCA bifurcation (n = 25, 19%) were the most frequent specific locations. Half (n = 11) of all fusiform aneurysms were found in the VB-PCA region. As many as 41 % of the giant MCA aneurysms were ruptured. Major anatomic variations were found in three (2%) and multiple giant aneurysms in three (2%) patients. Wall calcification was noted in 24% and intraluminal thrombosis in 33% of ruptured giant aneurysms (n = 42). CONCLUSIONS: The majority of giant aneurysms are located in the ICA and MCA regions, while the ACA region is an exceptional site. The MCA region is the most common site for ruptured giant aneurysms. Associated anatomic variations and the multiplicity of giant aneurysms are a rare finding.

Can homeopathy bring additional benefits to thalassemic patients on hydroxyurea therapy? Encouraging results of a preliminary study.

Several homeopathic remedies, namely, Pulsatilla Nigricans (30th potency), Ceanothus Americanus (both mother tincture and 6th potency) and Ferrum Metallicum (30th potency) selected as per similia principles were administered to 38 thalassemic patients receiving Hydroxyurea (HU) therapy for a varying period of time. Levels of serum ferritin (SF), fetal hemoglobin (HbF), hemoglobin (Hb), platelet count (PC), mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), mean corpuscular hemoglobin (MCH), white blood cell (WBC) count, bilirubin content, alanine amino transferase (ALT), aspartate amino transferase (AST) and serum total protein content of patients were determined before and 3 months after administration of the homeopathic remedies in combination with HU to evaluate additional benefits, if any, derived by the homeopathic remedies, by comparing the data with those of 38 subjects receiving only HU therapy. Preliminary results indicated that there was a significant decrease in the SF and increase in HbF levels in the combined, treated subjects. Although the changes in other parameters were not so significant, there was a significant decrease in size of spleen in most patients with spleenomegaly and improvement in general health conditions along with an increased gap between transfusions in most patients receiving the combined homeopathic treatment. The homeopathic remedies being inexpensive and without any known side-effects seem to have great potentials in bringing additional benefits to thalassemic patients; particularly in the developing world where blood transfusions suffer from inadequate screening and fall short of the stringent safety standards followed in the developed countries. Further independent studies are encouraged.

Membrane interactions of hemoglobin variants, HbA, HbE, HbF and globin subunits of HbA: effects of aminophospholipids and cholesterol.

The interaction of hemoglobin with phospholipid bilayer vesicles (liposomes) has been analyzed in several studies to better understand membrane-protein interactions. However, not much is known on hemoglobin interactions with the aminophospholipids, predominantly localized in the inner leaflet of erythrocytes, e.g., phosphatidylserine (PS), phosphatidylethanolamine (PE) in membranes containing phosphatidylcholine (PC). Effects of cholesterol, largely abundant in erythrocytes, have also not been studied in great details in earlier studies. This work therefore describes the study of the interactions of different hemoglobin variants HbA, HbE and HbF and the globin subunits of HbA with the two aminophospholipids in the presence and absence of cholesterol. Absorption measurements indicate preferential oxidative interaction of HbE and alpha-globin subunit with unilamellar vesicles containing PE and PS compared to normal HbA. Cholesterol was found to stabilize such oxidative interactions in membranes containing both the aminophospholipids. HbE and alpha-globin subunits were also found to induce greater leakage of membrane entrapped carboxyfluorescein (CF) using fluorescence measurements. HbE was found to induce fusion of membrane vesicles containing cholesterol and PE when observed under electron microscope. Taken together, these findings might be helpful in understanding the oxidative stress-related mechanism(s) involved in the premature destruction of erythrocytes in peripheral blood, implicated in the hemoglobin disorder, HbE/beta-thalassemia.

Spectrin interactions with globin chains in the presence of phosphate metabolites and hydrogen peroxide: implications for thalassaemia.

We have shown the differential interactions of the erythroid skeletal protein spectrin with the globin subunits of adult haemoglobin (HbA); these indicate a preference for alpha-globin over that for beta-globin and intact HbA in an adenosine 5'-triphosphate (ATP)-dependent manner. The presence of Mg/ATP led to an appreciable decrease in the binding affinity of the alpha-globin chain to spectrin and the overall yield of globin-spectrin cross-linked complexes formed in the presence of hydrogen peroxide. Similar effects were also seen in the presence of 2-,3-diphosphoglycerate (2,3 DPG), the other important phosphate metabolite of erythrocytes. The binding affinity and yield of cross-linked high molecular weight complexes (HMWCs) formed under oxidative conditions were significantly higher in alpha-globin compared with intact haemoglobin, HbA and the beta-globin chain. The results of this study indicate a possible correlation of the preferential spectrin binding of the alpha-globin chain over that of the beta-globin in the haemoglobin disorder beta-thalassaemia.

Does pelvic mesh treated with phosphorylcholine improve outcomes? An early experience.

OBJECTIVES: Implantable devices treated with phosphorylcholine (PC) have been successfully used in cardiac, ophthalmic, and other applications. This surface modification has resulted in a reduction in the host inflammatory responses. This pilot study tested the safety and efficacy of PC treated polypropylene mesh grafts implanted for the treatment of pelvic organ prolapse. STUDY DESIGN: Surgeons from five U.S. sites collected data on subjects implanted with Perigee IntePro Lite+PC. Pre-procedure data collected included demographics and prolapse severity. At follow-up, subjects were assessed for anatomical outcomes (success≤stage I POPQ or Baden Walker), symptomatic improvement, and complications, particularly mesh exposure. RESULTS: A total of 40 subjects were enrolled with 80% (32/40) of them completing at least 5-7 months of follow-up. Mean patient age was 60 years (range 36-78 years) and the mean BMI was 28 (range 20-40). There were no cases of mesh exposure/extrusion or granuloma formation. The anatomical success rate was 100% at 5-7 months (32/32). CONCLUSIONS: This is the first publication on pelvic mesh treated with PC. There were no adverse events attributed to this surface modification. However, as the numbers are small, the results are not statistically significant. PC surface modification of pelvic mesh shows promise in its application for the reduction of mesh related complications.

Interaction of erythroid spectrin with hemoglobin variants: implications in beta-thalassemia.

Among the few studies, producing contradictory results, done on the interaction of erythroid membrane skeletal spectrin with hemoglobin (Hb), none has been able to provide a quantitative estimate of the association of spectrin with Hb. In this work, studies on the interactions of erythroid spectrin with Hb have been elaborated upon using a novel fluorescence technique. The concentration-dependent change in the fluorescence intensity of fluorescein-conjugated spectrin (F-spectrin) in presence of oxy-Hb indicated binding with a dissociation constant of approximately 20 microM that has been directly evaluated from the increase in the extent of quenching of the fluorescein fluorescence of F-spectrin by reverse titration with the increasing concentrations of different Hb samples isolated from both normal and beta-thalassemic patients. The Hb compositions, with major components of the normal HbA, the fetal HbF, and the variant HbA2, of each individual were estimated using the Variant HPLC device of Bio-Rad. Results of the present study indicated that the dissociation constant, K(d), of spectrin binding to Hb decreased from 19.5 +/- 2 microM in normal individuals to of 6.5 +/- 0.5 microM in the presence of 73% HbA2 along with coeluted variants in the blood samples of patients suffering from beta-thalassemia, indicating differential interactions of the Hb variants with spectrin.

Crystallization and preliminary X-ray structural studies of hemoglobin A2 and hemoglobin E, isolated from the blood samples of beta-thalassemic patients.

Hemoglobin A(2) (alpha(2)delta(2)), a minor (2-3%) component of circulating red blood cells, acts as an anti-sickling agent and its elevated concentration in beta-thalassemia is a useful clinical diagnostic. In beta-thalassemia major, where there is a failure of beta-chain production, HbA(2) acts as the predominant oxygen delivery mechanism. Hemoglobin E, is another common abnormal hemoglobin, caused by splice site mutation in exon 1 of beta globin gene, when combines with beta-thalassemia, causes severe microcytic anemia. The purification, crystallization, and preliminary structural studies of HbA(2) and HbE are reported here. HbA(2) and HbE are purified by cation exchange column chromatography in presence of KCN from the blood samples of individuals suffering from beta-thalassemia minor and E beta-thalassemia. X-ray diffraction data of HbA(2) and HbE were collected upto 2.1 and 1.73 A, respectively. HbA(2) crystallized in space group P2(1) with unit cell parameters a=54.33 A, b=83.73 A, c=62.87 A, and beta=99.80 degrees whereas HbE crystallized in space group P2(1)2(1)2(1) with unit cell parameters a=60.89 A, b=95.81 A, and c=99.08 A. Asymmetric unit in each case contains one Hb tetramer in R(2) state.

Crystal structures of HbA2 and HbE and modeling of hemoglobin delta 4: interpretation of the thermal stability and the antisickling effect of HbA2 and identification of the ferrocyanide binding site in Hb.

Hemoglobin A(2) (alpha(2)delta(2)) is an important hemoglobin variant which is a minor component (2-3%) in the circulating red blood cells, and its elevated concentration in beta-thalassemia is a useful clinical diagnostic. In beta-thalassemia major, where there is beta-chain production failure, HbA(2) acts as the predominant oxygen deliverer. HbA(2) has two more important features. (1) It is more resistant to thermal denaturation than HbA, and (2) it inhibits the polymerization of deoxy sickle hemoglobin (HbS). Hemoglobin E (E26K(beta)), formed as a result of the splice site mutation on exon 1 of the beta-globin gene, is another important hemoglobin variant which is known to be unstable at high temperatures. Both heterozygous HbE (HbAE) and homozygous HbE (HbEE) are benign disorders, but when HbE combines with beta-thalassemia, it causes E/beta-thalassemia which has severe clinical consequences. In this paper, we present the crystal structures of HbA(2) and HbE at 2.20 and 1.74 A resolution, respectively, in their R2 states, which have been used here to provide the probable explanations of the thermal stability and instability of HbA(2) and HbE. Using the coordinates of R2 state HbA(2), we modeled the structure of T state HbA(2) which allowed us to address the structural basis of the antisickling property of HbA(2). Using the coordinates of the delta-chain of HbA(2) (R2 state), we also modeled the structure of hemoglobin homotetramer delta(4) that occurs in the case of rare HbH disease. From the differences in intersubunit contacts among beta(4), gamma(4), and delta(4), we formed a hypothesis regarding the possible tetramerization pathway of delta(4). The crystal structure of a ferrocyanide-bound HbA(2) at 1.88 A resolution is also presented here, which throws light on the location and the mode of binding of ferrocyanide anion with hemoglobin, predominantly using the residues involved in DPG binding. The pH dependence of ferrocyanide binding with hemoglobin has also been investigated.