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Mahesh Ramchandani

Publications and source records attributed to Mahesh Ramchandani.

7 recordsLinked to original sources

Relation of tissue Doppler-derived myocardial velocities to serum levels and myocardial gene expression of tumor necrosis factor-alpha and inducible nitric oxide synthase in patients with ischemic cardiomyopathy having coronary artery bypass grafting.

We evaluated the relation of segmental and annular tissue Doppler (TD) velocities to serum levels and myocardial gene expression of tumor necrosis factor-alpha (TNF-alpha) and inducible nitric oxide (NOS2) in humans. Seven patients with coronary artery disease underwent echocardiographic examination including TD imaging, along with transmural endomyocardial biopsies (2 biopsies per patient for a total of 14 specimens) at the time of bypass surgery. The specimens were analyzed for the number of mRNA copies of TNF-alpha and NOS2. In addition, serum levels of TNF-alpha and nitrite were determined before and after surgery. Normal segments (n = 7) had fewer numbers of mRNA copies of both TNF-alpha (54.6 vs 6.5, p = 0.002) and NOS2 (3,093 +/- 486 vs 661 +/- 259, p <0.001) than dysfunctional segments (n = 7). Peak systolic velocity (Sm) (13.3 +/- 1.4 vs 4.9 +/- 1.6 cm/s, p = 0.002) and early diastolic velocity (Em) (16.5 +/- 2.7 vs 8.8 +/- 1.3 cm/s, p = 0.02) were significantly higher in normal segments. A significant correlation was present among Em, Sm, and the number of mRNA copies of TNF-alpha and NOS2 at baseline and during infusion of dobutamine (r range -0.72 to -0.92, p <0.01 for all). Likewise, significant relations were present between the changes in serum cytokine levels and changes in the mitral annulus diastolic velocity, E/Ea ratio, and end-diastolic wall stress (r range 0.75 to 0.88, p </=0.05 for all). In conclusion, Sm and Em are strongly dependent on the regional levels of cytokine gene expression, which are known to have negative inotropic and lusitropic effects when overexpressed.

Aged↗

Active interstitial remodeling: an important process in the hibernating human myocardium.

OBJECTIVES: The purpose of this study is to investigate the morphologic characteristics of the cardiac interstitium in the hibernating human myocardium and evaluate whether active remodeling is present and is an important determinant of functional recovery. BACKGROUND: Myocardial hibernation is associated with structural myocardial changes, which involve both the cardiomyocytes and the cardiac interstitium. METHODS: We evaluated 15 patients with coronary disease with two-dimensional echocardiography and thallium-201 ((201)Tl) tomography before coronary bypass surgery. During surgery, transmural myocardial biopsies were performed guided by transesophageal echocardiography. Myocardial biopsies were stained immunohistochemically to investigate fibroblast phenotype and examine evidence of active remodeling in the heart. RESULTS: Among the 29 biopsied segments included in the study, 24 showed evidence of systolic dysfunction. The majority of dysfunctional segments (86.4%) were viable ((201)Tl uptake > or = 60%). After revascularization, 12 dysfunctional segments recovered function as assessed with an echocardiogram three months after bypass surgery. Interstitial fibroblasts expressing the embryonal isoform of smooth muscle myosin heavy chain (SMemb) were noted in dysfunctional segments, predominantly located in border areas adjacent to viable myocardial tissue. Segments with recovery had higher SMemb expression (0.46 +/- 0.16% [n = 12] vs. 0.10 +/- 0.02% [n = 12]; p < 0.05) and a higher ratio of alpha-smooth muscle actin to collagen (0.14 +/- 0.026 [n = 12] vs. 0.07 +/- 0.01 [n = 12]; p < 0.05) compared with segments without recovery, indicating fibroblast activation and higher cellularity of the fibrotic areas. In addition, interstitial deposition of the matricellular protein tenascin, a marker of active remodeling, was higher in hibernating segments than in segments with persistent dysfunction (p < 0.05), suggesting an active continuous fibrotic process. Multiple logistic regression demonstrated a significant independent association between SMemb expression and functional recovery (p < 0.01). CONCLUSIONS: Fibroblast activation and expression of SMemb and tenascin provide evidence of continuous remodeling in the cardiac interstitium of the hibernating myocardium, an important predictor of recovery of function after revascularization.

Aged↗

Evidence for an active inflammatory process in the hibernating human myocardium.

Myocardial hibernation refers to a state of prolonged impairment of left ventricular function in the presence of coronary artery disease, which may be reversed by revascularization. In this study we present evidence for a local inflammatory reaction in hibernating myocardial segments from patients undergoing coronary revascularization. We obtained transmural myocardial biopsies guided by transesophageal echocardiography from patients with ischemic ventricular dysfunction undergoing bypass surgery. Among the 28 biopsied segments included in the study, 23 showed evidence of systolic dysfunction. The majority of dysfunctional segments (85.7%) were viable ((201)Tl uptake >/= 60%). The samples were stained with markers for mast cells, mature resident macrophages, and the monoclonal antibody Mac387 that labels newly recruited myeloid cells. Dysfunctional segments showed more extensive fibrosis and higher macrophage density than normal segments. Among the 23 dysfunctional segments, 12 recovered function as assessed with echocardiograms 3 months after revascularization. Segments with postoperative functional recovery had comparable macrophage and mast cell density with those showing persistent dysfunction. However, biopsied segments that subsequently recovered function contained significantly higher numbers of newly recruited Mac387-positive leukocytes (18.7 +/- 3.1 cells/mm(2), n = 12 versus 8.6 +/- 0.9 cells/mm(2), n = 11; P = 0.009). In addition, monocyte chemotactic protein-1, a potent mononuclear cell chemoattractant, was predominantly expressed in segments with recovery of function. Myocardial hibernation is associated with an inflammatory response leading to active leukocyte recruitment. Dysfunctional myocardial segments that show an active inflammatory reaction have a greater potential for recovery of function after revascularization. We postulate that revascularization may promote resolution of the ongoing inflammation, preventing further tissue injury and fibrosis.

Aged↗

The danger of wearing an anorak.

Campaigns to reduce road traffic accidents have paid little attention to the way headgear could interfere with vision. Binocular visual field measurement was undertaken in six healthy volunteers wearing four different types of anorak. All four anoraks greatly reduced the horizontal and superior field of vision. The anorak producing the worst reduction resulted in a width of vision of 99 degrees and only 15 degrees of vision above eye level, versus 167 degrees and 52 degrees respectively without an anorak. Anorak wearers should turn their heads to look sideways before crossing the road.

Accidents, Traffic↗

Pooled cataract waiting lists: views of hospital consultants, general practitioners and patients.

In the National Health Service general practitioners (GPs) usually refer patients to named consultants; thus, waiting times for a particular procedure can vary greatly even within a single centre. An alternative is to pool the waiting list, with patients treated in turn by the consultant available. We sought opinions on this strategy, from patients, GPs, and consultants, in relation to cataract surgery. Questionnaires were sent to 776 consultant ophthalmologists; telephone interviews were conducted with 50 randomly selected Birmingham GPs; and 85 Birmingham patients listed for cataract surgery were asked whether they would change consultant to be operated on sooner. 503 (64%) of the consultants responded. Of consultants, 30% favoured pooled lists and 67% were against. Of patients, 82% favoured pooled lists and 18% were against. Of GPs, 92% favoured pooled lists and 8% were against. Some consultants thought that pooled lists were suitable for routine cases but not for more complex cases. 82% of patients expressed willingness to change consultant in order to get an earlier operation. In units with surgeons whose cataract-surgery practices are similar, pooled lists are one way to maximize theatre use and equalize waiting times for routine cases. The model could be applied to other routine surgical procedures such as hip replacement, herniorrhaphy and prostatectomy.

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