Clinical course of isolated ventricular septal defect: An Indian experience

To define the clinical course of ventricular septal defect, 410 consecutive patients with isolated ventricular septal defect were evaluated over a period of 13 years. Their age ranged from 12 days to 24 years at the time of first visit to the hospital. Patients with less than 2 years follow-up period were excluded. One hundred and fifty seven patients were one year of age or less. The left to right shunt size remained the same in 52.4% of cases. In 34.4% the shunt size decreased, with complete closure of ventricular septal defect in 8.8%. Closure of ventricular septal defect was observed even in patients who had initially presented with large left to right flow, and congestive heart failure in infancy. Right ventricular outflow tract obstruction developed in 8.5% of patients usually between 2 and 10 years of age. Murmur of aortic regurgitation appeared in 8.9% on follow-up. Infective endocarditis developed in 6 cases. The unfortunate complication of Eisemenger's complex was seen in 3 patients; they had not returned for follow up for a long period of time. Hence, our data show that the left to right shunt across the ventricular septal defect decreases in about one-third of patients. However, a regular follow up is essential to prevent development of Eisenmenger's complex and for early detection of other complications like aortic regurgitation and right ventricular outflow tract obstruction.     

Cellular responses of mammary carcinomas to aromatase inhibitors: Effects of vorozole

Vorozole (Vz) is a competitive non-steroidal inhibitor of aromatase, which has been used to treat breast cancer in postmenopausal women and in various chemoprevention pre-clinical studies. Recently, we assessed the inhibitory effect of Vz on Mnu-induced mammary carcinogenesis (Lubet et al., 1994), as well as on the progression of mammary tumors (Lubet et al., 1998). In this study we evaluated the effects of Vz on tumor growth, serum estradiol, cell proliferation, apoptotic and non-apoptotic cell death to determine whether any of these 'surrogate markers might reflect the efficacy of various doses of Vz. Vz at doses of 2.5 (Hi), 0.32 (Md), and 0.08 (Lo) mg/kg body weight induced complete (100%), 60%, and 20% regression of mammary tumors, respectively. Vz at Hi and Md doses caused a decrease in serum estradiol within the first two days of treatment, and the estradiol values remained low with additional treatment for 4 and 10 days. When Vz was administered to animals bearing palpable tumors a time and dose-dependent decrease in the proliferating cells (BrdU-LI) was observed. The percentage of apoptotic cells (Al) sharply increased 2 days after initiation of Vz treatment and then decreased followed by an increase in non-apoptotic dead cells. Interestingly even the Lo dose of Vz, which was only moderately effective in suppressing tumor growth, decreased cell proliferation and increased cell death in the peripheral tumor areas at 4 and 10 days after initiation of treatment. The time- and dose-dependent alterations in various cell parameters suggest two different phases of Vz-induced cellular responses: (1) an early phase (2–4 days of treatment) with a sharp increase in apoptotic cells and decrease in proliferating cells, and (2) a later phase (10 days) with disintegration of tumor parenchyma, increase in non-apoptotic dead cells, and decrease in apoptotic cells. The dose-dependent decrease in proliferating cells and increase in apoptotic and non-apoptotic cell death in Vz-treated animals suggest that these biomarkers might be used as potential surrogate endpoints for efficacy in breast cancer chemoprevention and therapy studies with aromatase inhibitors.     

POLYPEPTIDE MODELS OF COLLAGEN. SYNTHESIS OF (PRO-PRO-β-ALA)n

The sequential copolymer (Pro-Pro-β-Ala)_n has been synthesized as a model for collagen. Preliminary studies indicate that the polymer may bear conformational resemblance to collagen.     

Potential role of calmodulin-dependent phosphodiesterase in human brain tumor (review)

A wealth of knowledge exists regarding calmodulin-dependent phosphodiesterase (PDE1) in normal mammalian tissues. However, much remains to be known about the enzyme in human brain tumors (glioblastoma multiforme, GBM). PDE1 has not been investigated in GBM relative to normal brain and remains an important area of investigation. In this review, we have summarized the works that have been carried out in our laboratory on the potential role of PDE1 in GBM. In the normal brain, PDE1 is localized in all four principal parts of the brain: cerebrum, diencephalon, brainstem and cerebellum. Specifically, PDE1 is concentrated in anatomically distinct regions of the brain including the striatum, globus pallidus, substantia nigra, subiculum, Purkinjie cells, the external layer of the developing cerebellum and the cerebral cortex. In contrast, PDE1 is found to be very low in the GBM tissue compared to normal cerebral cortex tissue. However, the discovery of an inhibitor in the tumor tissue is interesting and definitely warrants further investigation, particularly, in relation to its possible interaction with PDE1.     

Giant aneurysm of the saphenous vein graft presenting as a mediastinal mass: a case report

We report a patient who presented initially with a diagnosis of a mediastinal mass. During the cardiac catheterization, the patient was diagnosed with a saphenous vein graft aneurysm. We proceeded with a catheter-based intervention resulting in occlusion of the aneurysm. Repeat angiogram after three months showed complete occlusion of the vein graft supplying the aneurysm. We believe that in selected patients with saphenous vein graft aneurysm a catheter-based procedure is feasible and successful.     

Plasma pseudocholinesterase: A potential marker for early detection of obesity

Plasma pseudocholinesterase activity, body weight and food intake showed significantly higher values in obese (ob/ob) mice than their lean littermates starting at the age of 35 days. The enzyme activity also showed a good positive correlation with age, body weight and food intake in all the mice from this age. Analysis of the data also indicated that between 35 and 58 days of age, pseudocholinesterase activity appeared to be more sensitive than body weight measurements in predicting obesity. Diabetic (db/db) mice on restricted diet, showed no significant difference in plasma pseudocholinesterase activity between the pre and post restricted blood samples. In contrast, diabetic mice on a non-restricted diet showed a significant increase in enzyme activity during the same interval of time. This suggests a relationship between hyperphagia, pseudocholinesterase and obesity.