Evaluation of stentangioplasty in university cardiac center

In this ongoing prospective study conducted in University Cardiac Center, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, from July 2004 to January 2006. Fifty (50) patients (mean age 56+/-7.2 years) underwent stentangioplasty were evaluated. The study group of 50 patients consisted of 42 (84%) men and 08 (16%) women. The aim of this study was to evaluate in-hospital success, failure and complications during the procedures. About risk factors 19(38%) had hypertension, 13(26%) were smoker, 11(22%) suffered from diabetes mellitus, 05(10%) had family history of ischaemic heart disease. Average left ventricular ejection fraction was 54+/-7. Target vessel percutaneous coronary angioplasty (PTCA) were done in 61 vessel, intracoronary stent implanted in 58 vessels, direct stenting were done in 35 cases, failed PTCA were in 03(6%) cases and two had dissection. The native vessels had a mean reference diameter of 2.91 mm and their luminal diameter increased significantly after percutaneous coronary intervention (PCI). All the patients were discharged by one to three days of the procedure with improvement of their clinical condition. In conclusion, intracoronary stent deployment in coronary artery stenosis following balloon angioplasty is a valid and beneficial strategy with good in-hospital results.     

The Heartfile Lodhran CVD prevention project--end of project evaluation

Mainstream preventive interventions often fail to reach poor populations with a high risk of cardiovascular diseases (CVDs) in Pakistan. A community-based CVD primary prevention project aimed at developing approaches to reduce risk factors in such populations was established by Heartfile in collaboration with the National Rural Support Program in the district of Lodhran. The project implemented a range of activities integrated with existing social and health service mechanisms during a three year intervention period 2000/01-03/04. These were targeted in 4 key settings: community health education, mass media interventions, training of health professionals and health education through Lady Health Workers. The project received support from the Department for International Development, U.K. At the community level, a pre-test-post-test quasi-experimental design was used for examining project outcomes related to the community component of the intervention. Pre and post-intervention (training) evaluations were conducted involving all health care providers in randomly selected workshops in order to determine baseline levels of knowledge and the impact of training on knowledge level. In order to assess practices of physician and non-physician health care providers patient interviews, with control comparisons were conducted at each health care facility. Significant positive changes were observed in knowledge levels at a community level in the district of intervention compared with baseline knowledge levels particularly in relation to a heart healthy diet, beneficial level of physical activity, the causes of high blood pressure and heart attack and the effects of high blood pressure and active and passive smoking on health. Significant changes in behaviors at a practice level were not shown in the district of intervention. However the project played a critical role in spurring national action for the prevention and control of non-communicable diseases and introducing sustainable public health interventions for poor communities in Pakistan.     

Cationic liposomes formulated with a novel whole Leishmania lysate (WLL) as a vaccine for leishmaniasis in murine model

Although there have been numerous attempts to develop a successful vaccine against leishmaniasis, based on the clinical trial in this field, no vaccine against Leishmania in routine way can be found for globally effective vaccination in human. Amongst, first generation vaccines consisting of parasite fractions or whole killed Leishmania showed more successful results in clinical trials. It seems that the main reason for the low efficacy of these vaccines is lack of a suitable adjuvant. In this study, a crude extract of detergent-solubilized L. major promastigotes as a novel developed antigen (whole Leishmania lysate (WLL)) was formulated in liposomal form. The cationic liposomes consisting of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) were used to deliver WLL. Liposomes formulations containing different WLL concentrations (prepared from 10³, 10⁴, 10⁵, 10⁶ and 10⁷ parasites) were prepared and characterized for particle size, surface charge, proteins, DNA and phospholipids contents. Moreover, to explore the type of immune response generated and extend of immunization, in vivo and in vitro tests including evaluation of lesion development, parasite burden in the foot and spleen, Th1 and Th2 cytokine analysis, and titration of IgG isotypes before and after the challenge were used. The maximum immunization was provided by WLL06 as depicted by the reduction of footpad swelling andparasite load, increase in anti-Leishmania IgG2a production, though no significant difference was observed between mice which received WLL05 vs WLL06. While maximum immunization was seen in WLL06 group, most of the liposomal WLL formulations induced a mixed Th1/Th2 response. Hence, a more protective immune response is expected to be induced when an immune potentiator adjuvant such as CpG ODNs would be co-deliverd in WLL liposomal formulations.     

The beta2 subunit inhibits stimulation of the alpha1/beta1 form of soluble guanylyl cyclase by nitric oxide. Potential relevance to regulation of blood pressure.

Cytosolic guanylyl cyclases (GTP pyrophosphate-lyase [cyclizing; EC 4.6.1.2]), primary receptors for nitric oxide (NO) generated by NO synthases, are obligate heterodimers consisting of an alpha and a beta subunit. The alpha1/beta1 form of guanylyl cyclase has the greatest activity and is considered the universal form. An isomer of the beta1 subunit, i.e., beta2, has been detected in the liver and kidney, however, its role is not known. In this study, we investigated the function of beta2. Immunoprecipitation experiments showed that the beta2 subunit forms a heterodimer with the alpha1 subunit. NO-stimulated cGMP formation in COS 7 cells cotransfected with the alpha1 and beta2 subunits was approximately 1/3 of that when alpha1 and beta1 subunits were cotransfected. The beta2 subunit inhibited NO-stimulated activity of the alpha1/beta1 form of guanylyl cyclase and NO-stimulated cGMP formation in cultured smooth muscle cells. Our results provide the first evidence that the beta2 subunit can regulate NO sensitivity of the alpha1/beta1 form of guanylyl cyclase. Northern analysis for guanylyl cyclase subunits was performed on RNA from kidneys of Dahl salt-sensitive rats, which have been shown to have decreased renal sensitivity to NO. Compared to the Dahl salt-resistant rat, message for beta2 was increased, beta1 was decreased, and alpha1 was unchanged. These results suggest a molecular basis for decreased renal guanylyl cyclase activity, i.e. , an increase in the alpha1/beta2 heterodimer, and decrease in the alpha1/beta1 heterodimer.     

Prevalence and risk factors for intrafamilial transmission of hepatitis C virus in Karachi,Pakistan

Household contacts of hepatitis C virus (HCV)-positive patients are considered at increased risk of HCV infection. This cross-sectional study during April through June 1999 assessed the prevalence and risk behaviours associated with HCV seropositivity among the household contacts of HCV seropositive thalassaemic children in Karachi, Pakistan. Among the 341 household contacts of 86 thalassaemic HCV seropositive children who were tested, 70 (20.5%) were positive for anti-HCV antibodies. The stratified analysis showed that HCV seroprevalence among the contacts did not differ significantly by the gender of the index patient and the type of relationship of contact with the index patient. However, HCV seroprevalences among the fathers and mothers of male index patients was substantially higher compared to those of female index patients. HCV RNA was recovered and genotyped from nine index patients and corresponding nine HCV-seropositive household contacts. HCV genotype 3a and 3b were found in 89% (8/9) and 11% (1/9) of the pairs, respectively. The final multivariable conditional logistic regression model revealed that after adjusting for the effect of ethnicity and past hospital admission history, the HCV-seropositive household contacts were more likely than HCV seronegative household contacts to have been bitten by the carrier [adjusted matched odds ratio (mOR)=2.6, 95% CI 1.3–5.2] or have shared a toothbrush with the carrier (adjusted mOR=8.2; 95% CI 1.56–43.5). Control efforts should focus on the risk behaviours.     

Efficacy of NovoSeven® during surgery on a haemophiliac with previous history of inhibitors

Management of bleeding in haemophiliacs with a history of inhibitor remains problematic. With infusion of factor VIII (FVIII), development of an anamnestic response and possible appearance of high-titre inhibitor remains a valid concern. We report a case of a haemophiliac with a history of moderately high-titre FVIII inhibitor that had become undetectable. He had not received FVIII since 1997, when he became inhibitor negative. He had been managed during his bleeding episodes with prothrombin complex factor concentrates, which became less effective in controlling his bleeding. The patient had a history of recurrent, spontaneous shoulder joint dislocations with bleeding, pain and significant disability. Shoulder joint replacement surgery was suggested. Replacement therapy was discussed with the patient, who refused treatment with human FVIII because of his concern for possible anamnestic response and inhibitor rebound. Porcine FVIII was not acceptable due to his poor response when used once in the past, and his history of moderate allergic reaction. Therefore, recombinant factor VIIa (NovoSeven, Novo Nordisk, Princeton, NJ) was considered to be an acceptable option for the contemplated shoulder surgery. The patient underwent 2.5 h of surgery with NovoSeven infusion. The surgeons were impressed with the lack of bleeding in this traumatic surgery. Despite the continuously prolonged activated partial thromboplastin time and low FVIII levels, the patient maintained a remarkably dry surgical field. Effective haemostasis was achieved during and after this procedure. This case illustrates the usage of NovoSeven as an effective treatment modality in a haemophilia A patient with past history of inhibitor undergoing joint surgery.     

A portable battery powered microfluidic impedance cytometer with smartphone readout: towards personal health monitoring

We present a portable system for personalized blood cell counting consisting of a microfluidic impedance cytometer and portable analog readout electronics, feeding into an analog-to-digital converter (ADC), and being transmitted via Bluetooth to a user-accessible mobile application. We fabricated a microfluidic impedance cytometer with a novel portable analog readout. The novel design of the analog readout, which consists of a lock-in-amplifier followed by a high-pass filter stage for subtraction of drift and DC offset, and a post-subtraction high gain stage, enables detection of particles and cells as small as 1 μm in diameter, despite using a low-end 8-bit ADC. The lock-in-amplifier and the ADC were set up to receive and transmit data from a Bluetooth module. In order to initiate the system, as well as to transmit all of the data, a user friendly mobile application was developed, and a proof-of-concept trial was run on a blood sample. Applications such as personalized health monitoring require robust device operation and resilience to clogging. It is desirable to avoid using channels comparable in size to the particles being detected thus requiring high levels of sensitivity. Despite using low-end off-the-shelf hardware, our sensing platform was capable of detecting changes in impedance as small as 0.032%, allowing detection of 3 μm diameter particles in a 300 μm wide channel. The sensitivity of our system is comparable to that of a high-end bench-top impedance spectrometer when tested using the same sensors. The novel analog design allowed for an instrument with a footprint of less than 80 cm². The aim of this work is to demonstrate the potential of using microfluidic impedance spectroscopy for low cost health monitoring. We demonstrated the utility of the platform technology towards cell counting, however, our platform is broadly applicable to assaying wide panels of biomarkers including proteins, nucleic acids, and various cell types.     

Extracellular forms of IL-37 inhibit innate inflammation in vitro and in vivo but require the IL-1 family decoy receptor IL-1R8

Similar to IL-1α and IL-33, IL-1 family member IL-37b translocates to the nucleus and is associated with suppression of innate and adaptive immunity. Here we demonstrate an extracellular function of the IL-37 precursor and a processed form. Recombinant IL-37 precursor reduced LPS-induced IL-6 by 50% (P < 0.001) in highly inflammatory human blood-derived M1 differentiated macrophages derived from selective subjects but not M2 macrophages. In contrast, a neutralizing monoclonal anti–IL-37 increased LPS-induced IL-6, TNFα and IL-1β (P < 0.01). The suppression by IL-37 was consistently observed at low picomolar but not nanomolar concentrations. Whereas LPS induced a 12-fold increase in TNFα mRNA, IL-37 pretreatment decreased the expression to only 3-fold over background (P < 0.01). Mechanistically, LPS-induced p38 and pERK were reduced by IL-37. Recombinant IL-37 bound to the immobilized ligand binding α-chain of the IL-18 receptor as well as to the decoy receptor IL-1R8. In M1 macrophages, LPS increased the surface expression of IL-1R8. Compared with human blood monocytes, resting M1 cells express more surface IL-1R8 as well as total IL-1R8; there was a 16-fold increase in IL-1R8 mRNA levels when pretreated with IL-37. IL-37 reduced LPS-induced TNFα and IL-6 by 50–55% in mouse bone marrow-derived dendritic cells, but not in dendritic cells derived from IL-1R8–deficient mice. In mice subjected to systemic LPS-induced inflammation, pretreatment with IL-37 reduced circulating and organ cytokine levels. Thus, in addition to a nuclear function, IL-37 acts as an extracellular cytokine by binding to the IL-18 receptor but using the IL-1R8 for its anti-inflammatory properties.IL-37, previously known as IL-1 family member 7, broadly reduces innate inflammation as well as acquired immune responses (1). In human peripheral blood mononuclear cells (PBMCs), a knockdown of endogenous IL-37 results in increased production of LPS- as well as IL-1β–induced cytokines (2). Mice transgenic for full-length human IL-37 (IL-37tg) are protected against LPS-induced systemic inflammation (2), chemical colitis (3), metabolic syndrome (4), and acute myocardial infarction (5). IL-37tg mice also have suppressed immune responses following challenge by specific antigen (6). We believe that full-length IL-37 expressed in the transgenic mice is processed extracellularly.In mouse macrophages stably transfected with human IL-37, ∼20% of IL-37 translocates to the nucleus (7), which is associated with decreased cytokine production (2, 7). However, in the presence of a caspase-1 inhibitor, there is no translocation to the nucleus and no reduction in LPS-induced cytokines (7). Mutation of aspartic acid at the caspase-1 cleavage position 20 to alanine also results in failure to translocate to the nucleus and loss of the suppression of cytokine production (8). Thus, as with IL-1α and IL-33, IL-37 is the third member of the IL-1 family that translocates to the nucleus and affects cellular responses. Nevertheless, it remains unclear whether the reduction in cytokines in vitro or in vivo is due solely to nuclear translocation of IL-37.Support for an extracellular function for IL-37 comes from early studies reported over 10 y ago that demonstrated binding of IL-37 to the α-chain of IL-18 receptor (IL-18Rα). We therefore hypothesized that extracellular IL-37 can function through the IL-18Rα surface receptor to mediate its anti-inflammatory effects but that a negative or decoy receptor would be required. The candidate decoy receptor would likely be IL-1R8 [formerly, single IgG IL-1–related receptor (SIGIRR)] because, similar to IL-18BP, IL-1R8 has only a single Ig domain and is known for providing a brake on inflammation (9). In the present study, we have characterized the function of full-length recombinant IL-37b in inhibiting inflammation in vitro and in vivo and the role of IL-1R8.     

Bilateral loss of light reflex and accommodation following 360° peripheral retinal laser therapy

We report a case of bilateral loss of pupillary light reflex and accommodation following 360° peripheral retinal laser therapy. A 24 years old male underwent prophylactic laser barrage for peripheral retinal lattice degenerations. Soon after the procedure, he developed bilateral loss of pupillary light reflex and accommodation. The patient faced difficulty while doing near work. On instillation of 0.125% pilocarpine, both pupils demonstrated the phenomenon of denervation supersensitivity. Damage to the short ciliary nerves was the most likely mechanism responsible for this adverse outcome.