Thermal Injury Prediction During Cryoplasty Through <Emphasis Type="Italic">In Vitro</Emphasis> Characterization of Smooth Muscle Cell Biophysics and Viability

Restenosis in peripheral arteries is a major health care problem in the United States. Typically, 30–40% of angioplasties result in restenosis and hence alternative treatment techniques are being actively investigated. Cryoplasty, a novel technique involving simultaneous stretching and freezing of the peripheral arteries (e.g., femoral, iliac, popliteal) using a cryogen-filled balloon catheter, has shown the potential to combat restenosis. However, evaluation of the thermal and biophysical mechanisms that affect cellular survival during cryoplasty is lacking. To achieve this, the thermal history in arteries was predicted for different balloon temperatures using a thermal model. Cellular biophysical responses (water transport (WT) and intracellular ice formation (IIF)) were then characterized, using in vitro model systems, based on the thermal model predictions. The thermal and biophysical effects on cell survival were eventually determined. For this study, smooth muscle cells (SMC) isolated from porcine femoral arteries were used in suspensions and attached in vitro systems (monolayer and fibrin gel). Results showed that for different balloon temperatures, the thermal model predicted cooling rates from 2200 to 5 °C/min in the artery. Biophysical parameters (WT & IIF) were higher for SMCs in attached systems as compared to suspensions. The “combined” fit WT parameters for SMCs in suspension (at 5, 10, and 25 °C/min) are L _pg = 0.12 μm/(min atm) and E _Lp = 24.1 kcal/mol. Individual WT parameters for SMCs in attached cell systems at higher cooling rates are approximately an order of magnitude higher compared to suspensions (e.g., at 130 °C/min, WT parameters in monolayer and fibrin TE systems are L _pg = 18.6, 19.4 μm/(min atm) and E _Lp = 112, 127 kcal/mol, respectively). Similarly, IIF parameters assessed at 130 °C/min are higher for SMCs in attached systems than suspensions ( = 1.1, 354, 378 (× 10⁸ (1/m² s)) and κ_o = 1.6, 1.8, 2.1 (× 10⁹ K⁵) for suspensions, monolayer, and fibrin TE, respectively). One possible reason for the differences in IIF kinetics was verified to be the presence of gap junctions, which facilitate cell–cell connections through which ice can propagate. This is reflected by the change in the predicted IIF parameters when a gap junction inhibitor was added and tested in monolayer ( (1/m² s)); κ_o = 2.1 × 10⁹ K⁵). SMC viability was affected by the model system (lower viability in attached systems), the thermal conditions and the biophysics. For e.g., IIF is lethal to cells and SMC viability was verified to be the least in fibrin TE (most % IIF) and the most in suspensions (least % IIF) at all cooling rates. Using the results from the fibrin TE (suggested as the best in vitro system to mimic a restenosis environment), conservative estimates of injury regimes in the artery during cryoplasty is predicted. The results can be used to suggest future optimizations and modifications during cryoplasty and also to design future in vivo studies.

Clinically significant hoarding in obsessive-compulsive disorder: results from an Indian study

Background

Hoarding is frequently conceptualized as a symptom of obsessive-compulsive disorder (OCD), but recent evidence indicates that, in most cases, hoarding may be better conceptualized as a distinct disorder that can coexist with OCD. Most of the research on hoarding is from the Western countries. This study aimed to provide data on the prevalence and correlates of clinically significant hoarding in a large sample of patients with OCD from the Indian subcontinent.

Methods

We examined 200 patients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition OCD for clinically significant hoarding using the Saving Inventory–Revised, followed by a clinical interview.

Results

Twenty patients (10%) had clinically significant hoarding. In all cases, hoarding did not appear to be related or secondary to other OCD symptoms. None of the cases consulted for their hoarding problems. Compared with nonhoarders, hoarders hailed exclusively from an urban background and had a significantly higher frequency of certain obsessions and compulsions, bipolar disorder, generalized anxiety disorder, cluster C personality disorders, and a higher number of lifetime suicidal attempts. They also had a more severe OCD along with poorer global functioning and somewhat poorer insight into obsessive-compulsive symptoms.

Conclusions

The results suggest that clinically significant hoarding is relatively prevalent in Indian patients with OCD and that it appears to be largely unrelated to the OCD phenotype. However, the presence of comorbid hoarding is associated with more severe OCD, high comorbidity, more suicidal attempts, and a lower level of functioning. The results contribute to the current nosologic debate around hoarding disorder and provide a unique transcultural perspective.     

Dietary factors in oral leukoplakia and submucous fibrosis in a population-based case control study in Gujarat, India

OBJECTIVES: To investigate the relationship of specific nutrients and food items with oral precancerous lesions among tobacco users.
DESIGN: A population-based case-control study. SETTING: Villages in Palitana taluk of Bhavnagar district, Gujarat, India.
SUBJECTS AND METHODS: An interviewer-administered food frequency questionnaire, developed and validated for this population, was used to estimate nutrient intake in blinded, house-to-house interviews. Among 5018 male tobacco users, 318 were diagnosed as cases. An equal number of controls matched on age (±5 years), sex, village, and use of tobacco were selected.
MAIN OUTCOME MEASURES: Odds ratios (OR) from multiple logistic regression analysis controlling for relevant variables (type of tobacco use and economic status).
RESULTS: A protective effect of fibre was observed for both oral submucous fibrosis (OSF) and leukoplakia, with 10% reduction in risk per g day^-1 ( P < 0.05). Ascorbic acid appeared to be protective against leukoplakia with the halving of risk in the two highest quartiles of intake (versus the lowest quartile: OR = 0.46 and 0.44, respectively; P < 0.10). A protective effect of tomato consumption was observed in leukoplakia and a suggestion of a protective effect of wheat in OSF.
CONCLUSION: In addition to tobacco use, intake of specific nutrients may have a role in the development of oral precancerous lesions.     

Relationship between corpus callosum abnormalities and schneiderian first-rank symptoms in antipsychotic-naive schizophrenia patients

The corpus callosum (CC), has been hypothesized to be implicated in the pathogenesis of schizophrenia; however, the findings from magnetic resonance imaging studies are conflicting. Moreover, the relationship between first-rank-symptoms (FRS) and CC abnormalities in schizophrenia is yet to be examined. The authors examined CC morphometry, based on Witelson's method, in antipsychotic-na?ve-schizophrenia patients in comparison with matched healthy-control subjects. Patients had significantly smaller CC, splenium, and isthmus areas than control subjects. A novel finding of the study is that only those without FRS differed from control subjects, but not those with FRS. Study findings support a neuro-developmental hypothesis and possible connectivity abnormalities in symptom-genesis.     

P2X7 Gene Polymorphisms and Risk Assessment for Pulmonary Tuberculosis in Asian Indians

Objective: Pulmonary tuberculosis (PTB) is a leading cause of morbidity and mortality. Macrophages play an important role in the immunopathogenesis of tuberculosis. Extracellular ATP induces macrophage bactericidal activity through activation of the purinergic P2X7 receptor. This case- control study assesses the association of −762 T/C, 1513A/C and 1729T/A P2X7 polymorphisms in patients with PTB and healthy controls to establish association if any with risk of developing the disease. Materials and methods: The genotyping for P2X7 was carried out using PCR and RFLP analysis in 256 individuals, which included 156 active PTB patients and 100 age and sex, matched healthy volunteers with no clinical symptoms or family history of PTB as controls. Results: A chi square test showed a significant difference between the PTB patient and controls for −762 C allele; p=0.0051 (OR 1.6972, CI 95% 1.1839 to 2.4332) and1729 T allele was found to be positively associated with the PTB; p < 0.0005 (OR-2.4623, CI 95% 1.6376 to 3.7022). 1513A/C polymorphism did not show any significant difference between the two groups. Significance: The study revealed a significant association of P2X7-762C allele and P2X7 1729T allele receptor polymorphisms with PTB in Asian Indian population. The use of these alleles as biomarkers for identifying individuals at high risk of developing TB needs to be ascertained.