Novel insight into the detailed myocardial motion and deformation of the rodent heart using high-resolution phase contrast cardiovascular magnetic resonance

Background

Phase contrast velocimetry cardiovascular magnetic resonance (PC-CMR) is a powerful and versatile tool allowing assessment of in vivo motion of the myocardium. However, PC-CMR is sensitive to motion related artifacts causing errors that are geometrically systematic, rendering regional analysis of myocardial function challenging. The objective of this study was to establish an optimized PC-CMR method able to provide novel insight in the complex regional motion and strain of the rodent myocardium, and provide a proof-of-concept in normal and diseased rat hearts with higher temporal and spatial resolution than previously reported.

Methods

A PC-CMR protocol optimized for assessing the motion and deformation of the myocardium in rats with high spatiotemporal resolution was established, and ten animals with different degree of cardiac dysfunction underwent examination and served as proof-of-concept. Global and regional myocardial velocities and circumferential strain were calculated, and the results were compared to five control animals. Furthermore, the global strain measurements were validated against speckle-tracking echocardiography, and inter- and intrastudy variability of the protocol were evaluated.

Results

The presented method allows assessment of regional myocardial function in rats with high level of detail; temporal resolution was 3.2 ms, and analysis was done using 32 circumferential segments. In the dysfunctional hearts, global and regional function were distinctly altered, including reduced global peak values, increased regional heterogeneity and increased index of dyssynchrony. Strain derived from the PC-CMR data was in excellent agreement with echocardiography (r = 0.95, p < 0.001; limits-of-agreement −0.02 ± 3.92%strain), and intra- and interstudy variability were low for both velocity and strain (limits-of-agreement, radial motion: 0.01 ± 0.32 cm/s and −0.06 ± 0.75 cm/s; circumferential strain: -0.16 ± 0.89%strain and −0.71 ± 1.67%strain, for intra- and interstudy, respectively).

Conclusion

We demonstrate, for the first time, that PC-CMR enables high-resolution evaluation of in vivo circumferential strain in addition to myocardial motion of the rat heart. In combination with the superior geometric robustness of CMR, this ultimately provides a tool for longitudinal studies of regional function in rodents with high level of detail.     

Efficacy and Tolerability of Topical Fixed Combination of Nadifloxacin 1% and Adapalene 0.1% in the Treatment of Mild to Moderate Acne Vulgaris in Indian Patients: A Multicenter,Open-Labelled,Prospective Study

Background:

A combination of topical retinoid and antibacterial therapy is often advocated for acne to enhance therapeutic efficacy.

Aims:

A preliminary study to evaluate the efficacy and tolerability of a topical fixed combination of nadifloxacin (1%) and adapalene (0.1%) in the treatment of mild to moderate acne in Indian patients.

Materials and Methods:

This was an open-labeled, phase 3 non-randomized, non-comparative study conducted at five centers (Ahmedabad, Nagpur, Thane, Bangalore, and Mumbai) across India. Of 119 enrolled patients with mild to moderate acne, 117 patients were evaluated at the end of the study for efficacy parameters. A fixed combination of nadifloxacin (1%) and adapalene (0.1%) topical gel was applied at the affected area once at night for a period of 8 weeks. Reduction in the total, inflammatory and non-inflammatory lesion counts from the baseline, investigator global assessment (IGA) and reduction in the severity of acne as per combined acne severity classification were the primary efficacy variables measured at 2 weeks, 4 weeks, and 8 weeks.

Results:

Overall, 98.3% patients showed a statistically significant progressive reduction in non-inflammatory lesion counts, inflammatory lesion counts, and total lesion counts over the study duration. By the end of 8 weeks, 75% of the patients had their global assessment scores approaching to normal healthy skin score. The adverse events were mild to moderate in severity.

Conclusion:

This preliminary study shows that a fixed combination of 1% nadifloxacin and 0.1% adapalene topical gel could be an effective and well-tolerated option for the treatment of mild to moderate acne vulgaris. However, further well-controlled, randomized and comparative evaluation of this combination is necessary.     

Plasminogen activators in normal tissue and carcinomas of the human oesophagus and stomach.

Carcinogenesis in the human colon is associated with a marked increase of urokinase type plasminogen activator and a decrease of tissue type plasminogen activator. This study was performed to determine the concentrations of urokinase type plasminogen activator and tissue type plasminogen activator in normal tissue and carcinomas along the upper part of the gastrointestinal tract. Activity and antigen levels of both activators were determined in homogenates of endoscopically obtained biopsies from normal and carcinomatous tissues. Although the concentrations of tissue type plasminogen activator and urokinase type plasminogen activator in normal squamous epithelium of the oesophagus were low compared with those in columnar epithelium from the stomach, the urokinase type plasminogen activator/tissue type plasminogen activator antigen ratio of the different locations showed hardly any difference. Significant but heterogeneous increases were found in urokinase type plasminogen activator concentrations of biopsy specimens originating from carcinomas of both epithelial cell types. A decrease in tissue type plasminogen activator concentrations, as found in human colon carcinomas, could only be shown in carcinomas of columnar epithelium origin but not in squamous cell carcinomas of the oesophagus. The increase of urokinase type plasminogen activator and urokinase type plasminogen activator/tissue type plasminogen activator antigen ratio and the decrease of tissue type plasminogen activator in the carcinomas did not show a significant correlation with known prognostic determinants as differentiation grade, TNM classification, intestinal metaplasia, inflammation, and ulceration. The heterogeneous increase of urokinase type plasminogen activator in oesophageal and stomach carcinomas, together with the recently described association of urokinase type plasminogen activator in tissue extracts of breast carcinomas with aggressiveness and prognosis, may be relevance to prognostic studies, may be of relevance to prognostic studies in oesophageal and gastric cancer.     

Seroprevalence of HCV and its co-infection with HBV and HIV among liver disease patients of South Tamil Nadu

AIM: To determine the seroprevalence of hepatitis C virus (HCV) and its co-infection with hepatitis B virus (HBV), hepatitis delta agent (HDV) and human immunodeficiency virus (HIV) among liver disease patients of south Tamil Nadu.METHODS: A total of 1012 samples comprising 512 clinically diagnosed cases of liver disease patients and 500 apparently healthy age and sex matched individuals were screened for Hepatitis C virus (anti HCV and HCV RNA), Hepatitis B virus (HBsAg), Hepatitis delta agent (anti HDV) and Human immuno virus (antibodies to HIV-1 and HIV-2) using commercially available enzyme linked immunosorbent assay kits. HCV RNA was detected by RT-PCR. Liver function tests like ALT, AST, GGT, ALP, bilirubin and albumin were also studied.RESULTS: The seroprevalence of HCV was found to be 5.6% among liver disease patients by ELISA. 27/512, 49/512 and 12/512 patients were positive for HIV, HBV & HDV respectively. Co-infection of HCV & HBV was found in 8 patients, with 6 for HCV & HIV and 4 for HCV, HBV & HIV co-infections. Sex-wise analysis showed that HIV, HCV & HBV and HCV & HIV co-infection was high among females whereas for HBV it was high in males. The mean ALT and AST in HCV positive cases were 42.1 ± 8.3 and 49 ± 10.1. In people co-infected with HCV & HBV or HCV & HIV or HCV, HBV & HIV the mean ALT of 58.0 ± 03.16, 56.78 ± 4.401 and 64.37 ± 4.01 respectively.CONCLUSION: We strongly recommend routine test of the blood for HCV in addition to HBV and HIV. We also recommend individualized counseling to identify those at risk and testing for those who want it. Improved surveillance and periodic epidemiological studies will have to be undertaken to monitor and prevent these blood-borne viruses.     

In Vitro Synergism of Ciprofloxacin and Cefotaxime against Nalidixic Acid-Resistant Salmonella enterica Serotypes Paratyphi A and Paratyphi B

Paratyphoid fever is considered an emerging systemic intracellular infection caused by Salmonella enterica serotypes Paratyphi A, B, and C. We performed in vitro time-kill studies on three clinical isolates of nalidixic acid-resistant Salmonella serotype Paratyphi (NARSP) with different concentrations of ciprofloxacin and cefotaxime to identify combinations of antibiotics with synergistic activity against paratyphoid fever. Furthermore, we identify the frequency of mutations to ciprofloxacin, cefotaxime, and rifampin resistance and also sequenced the gyrA, gyrB, parC, and parE genes to identify the cause of resistance in NARSP. When the activity of ciprofloxacin at 0.75× MIC (0.012 to 0.38 μg/ml) with cefotaxime at the MIC (0.125 to 0.25 μg/ml) against all three NARSP isolates was investigated, synergy was observed at 24 h, and the bacterial counts were reduced by >3 log₁₀ CFU/ml. This synergy was elongated for up to 72 h in two out of three isolates. When ciprofloxacin at 0.75× MIC (0.012 to 0.38 μg/ml) was combined with cefotaxime at 2× MIC (0.25 to 0.50 μg/ml), synergy was prolonged for up to 72 h in all three isolates. Both Salmonella serotype Paratyphi A isolates carried single mutations in codon 83 of the gyrA gene and codon 84 of the parC gene that were responsible for their reduced susceptibility to ciprofloxacin, while no mutations were found in the gyrB or parE gene. The ciprofloxacin-plus-cefotaxime regimen was very effective in reducing the bacterial counts at 24 h for all three isolates, and this combination therapy may be helpful in reducing the chance of the emergence of fluoroquinolone-resistant mutants in patients with severe paratyphoid fever.Enteric fever (typhoid fever and paratyphoid fever) is a systemic intracellular infection caused by Salmonella enterica serotype Typhi or Salmonella enterica serotype Paratyphi A, B, and C. Paratyphoid fever caused by S. Paratyphi is considered an emerging disease, as its incidence has increased alarmingly in recent years (29), causing more asymptomatic infections than S. Typhi. Now enteric fever is a major public health problem in many countries. It is endemic in the Indian subcontinent, Southeast Asia, and Africa, causing at least 22 million cases of illness each year and 200,000 deaths (21), and more than 5 million of these cases were due to S. Paratyphi A (19). According to the findings of a 12-month survey by Ochiai et al. (20), 14% of the cases of enteric fever in Indonesia were caused by S. Paratyphi; these rates were 15% in Pakistan, 24% in India, and 64% in China. Shirakawa et al. (28) reported that in Kathmandu, Nepal, enteric fever caused by S. Paratyphi A is more prevalent than that caused by S. Typhi. The outbreak of enteric fever due to S. Paratyphi in Guangxi Province in southeast China and the increasing rate of isolation of serotype Paratyphi in other areas may signal that S. Paratyphi A is an emerging pathogen in Asia (20).Since 1997, cases of infection with nalidixic acid-resistant Salmonella serotype Typhi (NARST) with decreased susceptibility to ciprofloxacin have been reported in many parts of the world and are now common in the Indian subcontinent and Southeast Asia (23). In Europe and Wales, high-level fluoroquinolone resistance in salmonellae is associated with foreign travel, especially to Southeast and South Asia (11). Some patients with typhoid fever caused by NARST that is susceptible to fluoroquinolones in vitro, according to current Clinical and Laboratory Standards Institute (CLSI) interpretive criteria, can show a delayed response to ciprofloxacin or treatment failure or can even be refractory to treatment both clinically and bacteriologically (26). The failure of treatment with fluoroquinolones in the cases of S. Typhi and S. Paratyphi A in the Indian subcontinent and Southeast and Central Asia due to decreased susceptibility to ciprofloxacin is now a serious concern (30). Fluoroquinolone-resistant S. Paratyphi A has already been reported in Japan (1), as has the relapse of an S. Paratyphi B infection in a child after treatment with ciprofloxacin (7). Fluoroquinolone resistance in most bacterial isolates is due to mutations in the genes encoding DNA gyrase (gyrA, gyrB) or DNA topoisomerase IV (parC, parE) (10). Additionally, increased efflux activity is also a major mechanism of resistance in many Gram-negative bacteria, including Salmonella (9). Currently, however, there is no treatment of choice for patients infected with multidrug-resistant (MDR) and nalidixic acid-resistant Salmonella enterica serotype Paratyphi (NARSP) (24). Indeed, clinicians recommend either the longer-duration use of high-dose fluoroquinolone or the expanded-spectrum drugs cephalosporin or azithromycin, or the combination of these regimens, for the treatment of NARST and NARSP infections. To date, however, no time-kill studies have demonstrated the efficacy of such combination therapy for NARSP infections.We conducted time-kill studies on three clinical isolates, including an isolate from a patient at Chosun University Hospital infected with S. Paratyphi A and one isolate each of S. Paratyphi A and B obtained from the South Korea Center for Disease Control and Prevention (KCDC). In addition, we investigated the association of quinolone resistance with mutations in the genes coding for gyrase A and topoisomerase IV in these isolates.     

Thiamine responsive megaloblastic anemia syndrome

Thiamine responsive megaloblastic anemia syndrome (TRMA) is a clinical triad characterized by thiamine-responsive anemia, diabetes mellitus and sensorineural deafness. We report a 4-year-old girl with TRMA whose anemia improved following administration of thiamine and this case report sensitizes the early diagnosis and treatment with thiamine in children presenting with anemia, diabetes and deafness.     

Partial splenic embolization in a child with Gaucher disease,massive splenomegaly and severe thrombocytopenia

A 13-month-old boy with Gaucher disease presented with severe thrombocytopenia, anemia and massive splenomegaly. In addition he had significant respiratory compromise caused by abdominal compartment syndrome, requiring mechanical ventilation. Because of the degree of respiratory compromise and his existing bone marrow suppression, splenic artery embolization was chosen as an alternative to splenectomy. Splenic artery embolization was performed using 355–500-μm polyvinyl alcohol particles, with 70% ablation achieved. Within 24 h of the procedure the platelet count had risen to greater than 70,000/mm³ and to more than 170,000/mm³ on postoperative day 4. At the 8-month follow-up the splenic size had decreased from 18 cm to 8 cm, with a platelet count of 578,000/mm³. Partial splenic embolization provides a minimally invasive alternative to splenectomy in patients with Gaucher disease with massive splenomegaly and bone marrow suppression.