Serial intravascular ultrasonic study of outcomes of coronary culprit lesions with plaque rupture following bare metal stent implantation in patients with angina pectoris

Coronary culprit lesions with plaque rupture (PR) have been treated with different coronary interventions. However, it is unknown whether the presence of PR affects the restenotic process after coronary intervention. One hundred forty-two patients undergoing coronary bare metal stent implantation were enrolled in the present retrospective analysis. Case selection was based on availability of intravascular ultrasound (IVUS) and quantitative coronary angiographic examinations at baseline (before and after intervention) and at follow-up. Serial comparative analyses included qualitative and quantitative features of the culprit lesion and reference segments. PR was defined as an intraplaque cavity in communication with the lumen in the presence of a residual, disrupted cap. Patients were categorized according to the presence/absence of PR. Pre-interventional IVUS detected PR in 54 patients (38%). Baseline patient demographics were similar between the +PR and -PR groups. Quantitative IVUS analysis showed higher rates of positive remodeling and larger vessel and plaque areas in the +PR compared with -PR lesions (p <0.001 for all). At follow-up (7.2 +/- 2.6 months), no statistically significant difference was observed between the 2 groups in quantitative coronary angiographic or IVUS measurements. In conclusion, culprit lesions with PR exhibited larger plaque mass and higher rates of positive remodeling at preintervention IVUS examination. However, when treated with bare metal stents, the absence/presence of preintervention PR was not found to affect the rate or severity of in-stent restenosis in these culprit lesions.     

Pregnancy-Associated Plasma Protein A Levels in Late First Trimester Pregnancies with Small-for-Gestational Age Neonates: A Prospective Case–Control Study

Objective

We aimed to investigate the association of pregnancy associated plasma protein A (PAPP-A) levels in late first trimester with small for gestational age (SGA) neonates and adverse pregnancy outcomes in a low-income setting.

Methods

The inclusion criteria were late first trimester (11–13 + 6 weeks) women with singleton and non-anomalous pregnancy. Enrolled participants were sampled for PAPP-A and prospectively followed up for delivery outcome and antenatal complications. A multiple of median (MoM) was calculated and statistically compared between groups.

Results

Out of total 284 subjects, 14.54% delivered SGA babies and formed cases (Group A), 66.5% delivered appropriate for gestational age (AGA) neonates with uneventful antenatal period (controls, Group B), and 19.3% were AGA group with adverse pregnancy complications (Group C). The late first trimester median PAPP-A MoM was significantly lower (0.61) in Group A compared to Group B (1.47). Using receiver operating characteristic (ROC) curve for PAPP-A MoM, optimal cutoff value was found at 0.45 MoM, with positive predictive value of 56.2%, specificity of 92.6% and sensitivity of 45%. The median interquartile range (IQR) of PAPP-A MoM value in Group C in comparison with Group B was significantly lower except for abruption. At PAPP-A MoM cutoff value <1, <0.8, <0.6 and <0.4, the odds ratio for adverse pregnancy outcome was 8.30, 7.29, 10.97 and 10.60, respectively, indicating an inverse relationship.

Conclusion

With 0.45 MoM cutoff of PAPP-A, the detection rate, specificity and positive predictive value for SGA were 45, 92.6 and 56.2%, respectively. As PAPP-A MoM values decreased, the odds ratio of having adverse pregnancy outcomes increased.

     

Urodynamic evaluation in primary enuresis: an investigative and treatment outcome correlation

A prospective study was done in pediatric out-patient department of a tertiary care hospital to evaluate the role of urodynamics in the management of primary enuresis in the 5-14-year-old children and to compare the effectiveness of multidimensional behavioral therapy with pharmacological therapy. Hundred and nineteen children between 5-14 years with primary enuresis were evaluated clinically and investigated. Three patients with obvious organic causes were then excluded. The remaining patients were given either behavioral or pharmacological treatment on the basis of urodynamic assessment. Urodynamic abnormalities were seen in 80/116 (68.9%) patients namely uninhibited bladder contraction 50/116 (43.1%), small bladder capacity 20/116 (17.2%), large bladder capacity 4/116 (3.4%), decreased bladder compliance 3/116 (2.5%) and detrusor sphincter dyssenergia 3/116 (2.5%). Combination of abnormal micturition history stating daytime urgency or frequency or dysfunctional voiding symptoms like squatting and/or abnormal voiding charts could predict abnormal results of urodynamics correctly with sensitivity of 81% and specificity of 86.2%. Ultrasound identified only 38/80 enuretics with urodynamic abnormalities although it was 100% specific. Additionally one patient who was identified as having a small bladder capacity on voiding chart was seen to have mild pelvicalyceal dilatation on ultrasound and subsequently on urodynamic assessment was found to have Detrusor sphincter dyssenergia (DSD). Behavioral therapy as compared to drug therapy produced more complete remission (17/18 vs. 14/18) and lesser relapse rate (2/17 vs. 5/14) in monosymptomatic enuretics with normal urodynamics. In patients with urodynamic abnormality, response rates with behavioral therapy, imipramine, oxybutynin and flavoxate were 73.9% (CI 56-91.8%), 89.4% (CI 75.7-100%), 94.2% (CI 84.7-100%) and 89.4% (CI 75.7-100%), respectively. Specific drug therapy as per the urodynamic abnormality was significantly more effective 49/57 [86% (CI 77-95%)] vs 17/23 [73.9% (CI 56.1-91.9%)] at P < 0.05 than behavioral therapy in patients with underlying abnormal urodynamics. Micturition history and voiding chart can be used as screening tool for enuretics. Behavioral therapy should be the first line treatment for mono symptomatic and drug therapy for polysymptomatic enuretics. Urodynamic testing may be reserved for polysymptomatic enuretics with abnormal ultrasound or those who fail to respond to first line treatment.     

Development and Evaluation of a Novel Drug in Adhesive Transdermal System of Levodopa and Carbidopa

Purpose

Administration of levodopa along with carbidopa increases the availability of dopamine in the mid-brain, and this combination thereby is used in the treatment of parkinsonism. However, concomitant delivery of levodopa with carbidopa in oral therapy is limited by several issues and an alternative route would be advantageous. The current study assesses the feasibility of co-administration of levodopa and carbidopa through skin using a drug in adhesive transdermal system.

Methods

Drug in adhesive transdermal system containing levodopa (5 % w/w) and carbidopa (2.5 % w/w) (1 cm² area) was fabricated and assessed for in vitro drug release, ex vivo permeation, and in vivo pharmacokinetics in rat model.

Results

In vitro dissolution profiles indicated a biphasic pattern with an initial burst effect for both levodopa and carbidopa, although the drug release rate was relatively higher for carbidopa. Ex vivo permeation studies showed higher steady-state flux for levodopa (53.77?±?6.94 μg/cm²/h) and carbidopa (23.81?±?4.06 μg/cm²/h). In vivo studies revealed that the concomitant transdermal delivery of levodopa with carbidopa significantly changed the pharmacokinetic parameters of levodopa.

Conclusions

Given the promising results, this study concludes that the transdermal delivery route could be a feasible alternative to oral therapy for the successful delivery of levodopa in Parkinson’s disorder.