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Biomedical subjects

R Kumar

Publications and source records attributed to R Kumar.

At least 361 records · Page 20Linked to original sources

Increased frequency of LOH on chromosome 9 in sporadic primary melanomas is associated with increased patient age at diagnosis.

We carried out statistical analysis of the frequency of loss of heterozygosity (LOH) at 10 microsatellite markers on chromosome 9. In 44 microdissected sporadic primary melanomas a comparison of LOH frequency data with other patient data, like age at diagnosis and tumour thickness, showed an interesting correlation between patient age at diagnosis and frequency of LOH on chromosome 9. The patient group with age >72 years at diagnosis (n = 22, mean age 82.3 +/- 6.0 years, mean LOH 3.4 +/- 2.3) showed significantly increased LOH frequency (OR 3.1, 95% CI 1.8-5.3; chi(2) test, P < 0.0001) compared with age group </=72 years (n = 22, mean age 56.1 +/- 14.5 years, mean LOH 1.8 +/- 1.7). A statistically significant increased frequency of LOH (OR 3.5, 95% CI 1.5-7.9; chi(2) test, P = 0.03 after Bonferroni correction) was found only at marker D9S736 on 9p22 (telomeric to the INK4-ARF locus) relative to other markers on six different chromosomes. No other marker, including those located within the INK4-ARF locus, showed a statistically significant increased frequency of LOH. Our results for the first time show a non-random tendency for increased allelic loss in melanomas with increased patient age at diagnosis, besides supporting the existence of an additional tumour suppressor gene(s) on chromosome 9.

Adult↗

Brown tumor of the sternum: a potential source of false-positive Tl-201 and Tc-99m subtraction imaging in the mediastinum.

Tl-201 and Tc-99m subtraction imaging is a well-established technique for detecting parathyroid adenomas. We report a case of a brown tumor of the upper sternum mimicking an ectopic mediastinal parathyroid adenoma on Tl-201 and Tc-99m subtraction imaging in a patient with hyperparathyroidism. This brown tumor showed Tl-201 uptake but not Tc-99m uptake and thus did not subtract out in this scan.

Adenoma↗

Dual thyroid ectopy: case report and review of the literature.

Dual ectopic thyroid glands rarely occur, and only six cases have been reported in the literature. The authors describe a 14-year-boy who had a midline neck swelling for 8 to 9 years. The swelling increased gradually, but he had no pressure symptoms. The thyroid hormone profile showed a moderately increased thyroid-stimulating hormone value and normal T3 and T4 levels. A Tc-99m sodium pertechnetate thyroid scan showed dual ectopic thyroid glands in the sublingual and subhyoid regions.

Adolescent↗

Nephroptosis: the Tc-99m glucoheptonate scan as a diagnostic method.

A 40-year-old man was examined because he was a potential "healthy" renal donor. However, the routine work-up before surgery revealed hypertension, although there was no family history of this condition. The patient was examined to exclude secondary causes of hypertension. Tc-99m glucoheptonate renal imaging showed nephroptosis of the right kidney when the patient was standing, and this may have been the cause of the hypertension.

Adult↗

Thyroid hemangioma: a case report with a review of the literature.

A 53-year-old man was found serendipitously to have increased blood-pool uptake in the right lobe of the thyroid during a radionuclide ventriculography study for left ventricular function. Primary thyroid hemangioma is a rare condition, with only two cases reported in the literature. Secondary hemangioma may occur as a result of fine-needle aspiration. This technique may cause hematoma formation, which generally resolves normally, but on rare occasions it can lead to cavernous hemangioma formation. In patients with a thyroid swelling who have a cold nodule on a thyroid scan and only blood on repeated fine-needle aspiration, Tc-99m erythrocyte blood-pool imaging may be performed to diagnose hemangioma.

Hemangioma↗

Individual kidney glomerular filtration rate in the interpretation of non-diagnostic curves on captopril renography.

Captopril renography is known to have low sensitivity in the detection of renovascular disease in patients with bilateral renovascular disease and in patients with unilateral renovascular disease with a small kidney. In these groups of patients, we have tried to make the standard captopril renogram more objective by simultaneously estimating the individual kidney glomerular filtration rate (IKGFR). Twenty-five patients (10 bilateral, 15 unilateral) with angiographically proven renal artery stenosis (RAS) were studied. Ten renal units in five hypertensive patients with normal renal arteries were used as controls. A fall of more than 10% in IKGFR post-captopril was considered a positive result. The sensitivities of renogram and IKGFR in patients with bilateral RAS were 52.9% and 88.2% respectively. In patients with unilateral RAS, the sensitivities of renogram and IKGFR were 30% and 80% respectively. A significant fall in IKGFR was noted in eight of the 15 'normal' renal units of the unilateral RAS group. In conclusion, individual kidney GFR estimation in combination with captopril renography improved significantly the sensitivity in patients with symmetrical bilateral RAS and unilateral RAS with a small, poorly functioning kidney. A fall in GFR in the normal counterpart of a unilateral RAS kidney may be indicative of ongoing damage in the non-involved kidney.

Adolescent↗

Neuroendoscopic procedures: anesthetic considerations for a growing trend: a review.

The recent trend in neurosurgery is shifting toward further reduction in invasiveness to minimize trauma to the brain. Endoscopy holds the promise of shortened hospital stay with improved postoperative outcome. An important minimally invasive technique is neuroendoscopy. The ventricular system and subarachnoid space of the brain provide suitable conditions for the use of an endoscope. The currently available literature focuses only on recent advances in neuroendoscopy from the surgical perspective. To date, there is paucity of anesthetic literature emphasizing the implications for this growing trend. The surgical technique, instrumentation, anesthetic requirements, potential pitfalls and complications of this technique must be completely understood to ensure a successful outcome. The purpose of this review is to provide knowledge of indications, instrumentation, and anesthetic considerations in anticipation of complications steming from this procedure.

Anesthesia↗

Typhoid carriers among patients with gallstones are at increased risk for carcinoma of the gallbladder.

OBJECTIVE: The aim of this study was to identify risk factors for carcinoma of the gallbladder (CaGB) among patients with gallstones (GS) with special reference to role of chronic Salmonella typhi carrier state. METHODS: A prospective case-control study was conducted in a tertiary care center in India. Cases were defined as consecutive patients with CaGB and GS, whereas controls were patients with GS alone. All were assessed clinically and their demographic data, diet, and smoking history recorded. Patients were detected to be typhoid carriers on the basis of Vi serology by enzyme linked immunosorbent assay. Cases (n = 37) and controls (n = 80) were compared by univariate and logistic regression analysis. RESULTS: The mean age of the cases and the controls were 53.4 +/- 11 yr and 43.5 +/- 14 yr, respectively. Among the cases, six (16%) patients were detected to be typhoid carriers, in contrast to two (2.5%) among controls (p = 0.01). Compared to controls, cases were more often older (p = 0.0002), of a lower socioeconomic status (p = 0.0005), and smokers (p = 0.0002). Stepwise logistic regression analysis identified typhoid carrier state (OR = 14; CI 2-92), age > or =47 yr (OR = 5; CI 2-14) and smoking (OR = 11; CI 2-71) as the three independent risk factors for development of CaGB among patients with GS. CONCLUSION: Chronic typhoid carrier state was the most important risk factor among patients with CaGB and gallstones.

Adult↗

Generalized thermoelastic waves in homogeneous isotropic plates

The propagation of thermoelastic waves in homogeneous isotropic plate subjected to stress-free and rigid insulated and isothermal conditions is investigated in the context of conventional coupled thermoelasticity (CT), Lord-Shulman (LS), Green-Lindsay (GL), and Green-Nagdhi (GN) theories of thermoelasticity. Secular equations for the plate in closed form and isolated mathematical conditions for symmetric and skew-symmetric wave mode propagation in completely separate terms are derived. It is shown that the motion for SH modes gets decoupled from the rest of the motion and remains unaffected due to thermo-mechanical coupling and thermal relaxation effects. The phase velocities for SH modes have also been obtained. The results for coupled and uncoupled theories of thermoelasticity have been obtained as particular cases from the derived secular equations. At short wavelength limits the secular equations for symmetric and skew-symmetric waves in a stress-free insulated and isothermal plate reduce to Rayleigh surface waves frequency equations. Finally, the numerical solution is carried out for aluminum-epoxy composite material and the dispersion curves for symmetric and skew-symmetric wave modes are presented to illustrate and compare the theoretical results.

Journal Article↗

Evidence of Rab3A expression, regulation of vesicle trafficking, and cellular secretion in response to heregulin in mammary epithelial cells.

Heregulin beta1 (HRG), a combinatorial ligand for human growth factor receptors 3 and 4, is a regulatory polypeptide that promotes the differentiation of mammary epithelial cells into secretory lobuloalveoli. Emerging evidence suggests that the processes of secretory pathways, such as biogenesis and trafficking of vesicles in neurons and adipose cells, are regulated by the Rab family of low-molecular-weight GTPases. In this study, we identified Rab3A as a gene product induced by HRG. Full-length Rab3A was cloned from a mammary gland cDNA library. We demonstrated that HRG stimulation of human breast cancer cells and normal breast epithelial cells induces the expression of Rab3A protein and mRNA in a cycloheximide-independent manner. HRG-mediated induction of Rab3A expression was blocked by an inhibitor of phosphatidylinositol 3-kinase but not by inhibitors of mitogen-activated protein kinases p38(MAPK) and p42/44(MAPK). Human breast epithelial cells also express other components of regulated vesicular traffic, such as rabphilin 3A, Doc2, and syntaxin. Rab3A was predominantly localized in the cytosol, and HRG stimulation of the epithelial cells also raised the level of membrane-bound Rab3A. HRG treatment induced a profound alteration in the cell morphology in which cells displayed neuron-like membrane extensions that contained Rab3A-coated, vesicle-like structures. In addition, HRG also promoted the secretion of cellular proteins from the mammary epithelial cells. The ability of HRG to modify exocytosis was verified by using a growth hormone transient-transfection system. Analysis of mouse mammary gland development revealed the expression of Rab3A in mammary epithelial cells. Furthermore, expression of the HRG transgene in Harderian tumors in mice also enhanced the expression of Rab3A. These observations provide new evidence of the existence of a Rab3A pathway in mammary epithelial cells and suggest that it may play a role in vesicle trafficking and secretion of proteins from epithelial cells in response to stimulation by the HRG expressed within the mammary mesenchyma.

Animals↗

Reduced synthesis of muscle proteins in chronic renal failure.

Muscle wasting and weakness occur frequently in patients with chronic renal failure. The mechanism(s) by which these abnormalities occur is unclear. We hypothesized that such findings were due to defective muscle protein synthesis. We measured synthetic rates of mixed muscle proteins, myosin heavy chain, and mitochondrial proteins in serial muscle biopsy samples during a continuous infusion of L[1-(13)C]leucine from 12 patients with chronic renal failure and 10 healthy control subjects under identical study conditions. Patients with chronic renal failure have significantly lower synthetic rates of mixed muscle proteins and myosin heavy chain (27 and 37% reductions, respectively, P < 0.05 and P < 0.02). Significant declines in the synthetic rates of muscle mitochondrial protein (27%) (P < 0.05), muscle cytochrome c-oxidase activity (42%) (P < 0.007), and citrate synthase (27%) (P < 0.007) were also observed in patients with chronic renal failure. The synthetic rates of muscle proteins and activity of mitochondrial enzymes were negatively correlated to the severity of renal failure. These results indicate that in chronic renal failure there is a decrease in the synthesis of muscle contractile and mitochondrial proteins and a decrease in muscle mitochondrial oxidative enzymes. Reduced synthetic rate of several muscle proteins is the likely biochemical basis of muscle loss and muscle weakness in people with chronic renal failure.

Adult↗

Measurements of calcium transients in ventricular cells during discontinuous action potential conduction.

The L-type calcium current (I(Ca)) is important in sustaining propagation during discontinuous conduction. In addition, I(Ca) is altered during discontinuous conduction, which may result in changes in the intracellular calcium transient. To study this, we have combined the ability to monitor intracellular calcium concentration ([Ca(2+)](i)) in an isolated cardiac cell using confocal scanning laser fluorescence microscopy with our "coupling clamp" technique, which allows action potential propagation from the real cell to a real-time simulation of a model cell. Coupling a real cell to a model cell with a value of coupling conductance (G(C) = 8 nS) just above the critical value for action potential propagation results in both an increased amplitude and an increased rate of rise of the calcium transient. Similar but smaller changes in the calcium transient are caused by increasing G(C) to 20 nS. The increase of [Ca(2+)](i) by discontinuous conduction is less than the increase of I(Ca), which may indicate that much of [Ca(2+)](i) is the result of calcium released from the sarcoplasmic reticulum rather than the integration of I(Ca).

Action Potentials↗

Electrical interactions between a real ventricular cell and an anisotropic two-dimensional sheet of model cells.

We have extended our "coupling clamp" technique, in which we couple a real cell to a real-time simulation of a model cell, to now incorporate a real cardiac cell as the central element of a two-dimensional sheet of model cells, in which the coupling conductances may be different in the x and y directions and a specific region of lack of coupling conductance may serve as a resistive barrier. We stimulated the real cell in the central location and determined the critical size of the real cell for successful activation of the entire sheet. We found that this critical size was decreased when anisotropy was present compared with the isotropic case and was further decreased when the central site of stimulation was close to the resistive barrier. The heart normally has some degree of anisotropy, and it has been shown that the remodeling that occurs in peri-infarction zones produces a particular loss of lateral connections compared with end-to-end connections among heart cells. We propose that the normal existence of anisotropy and enhancement of the degree of anisotropy both by loss of lateral gap junctions and the development of resistive barriers may play a facilitating role in the development of ectopic foci that may lead to cardiac arrhythmias.

Animals↗

A spontaneously active focus drives a model atrial sheet more easily than a model ventricular sheet.

Tachycardias can be produced when focal activity at ectopic locations in either the atria or the ventricles propagates into the surrounding quiescent myocardium. Isolated rabbit atrioventricular nodal cells were coupled by an electronic circuit to a real-time simulation of an array of cell models. We investigated the critical size of an automatic focus for the activation of two-dimensional arrays made up of either ventricular or atrial model cells. Over a range of coupling conductances for the arrays, the critical size of the focus cell group for successful propagation was smaller for activation of an atrial versus a ventricular array. Failure of activation of the arrays at smaller focus sizes was due to the inhibition of pacing of the nodal cells. At low levels of coupling conductance, the ventricular arrays required larger sizes of the focus due to failure of propagation even when the focus was spontaneously active. The major differences between activation of the atrial and ventricular arrays is due to the higher membrane resistance (lower inward rectifier current) of the atrial cells.

Animals↗

Fast pacing facilitates discontinuous action potential propagation between rabbit atrial cells.

We examined the critical coupling conductance (G(C)) for propagation at different pacing cycle lengths (CLs) (1,000 and 400 ms). As G(C) was progressively reduced, propagation failed at a CL of 1,000 ms, whereas propagation succeeded at a CL of 400 ms over a range of G(C) values before failing at a CL of 400 ms at a lower G(C), showing facilitation of propagation at the shorter CL. Critical G(C) was (means +/- SE) 0.8 +/- 0.1 nS for a CL of 400 ms and 1.3 +/- 0.1 nS for a CL of 1,000 ms (a 63% increase, P < 0.002, n = 9 cell pairs). In 14 uncoupled cells, action potential duration at 30% repolarization (APD(30)) increased from 19.9 +/- 2.5 to 41.8 +/- 2.6 ms (P < 0.001) as CL decreased from 1,000 to 400 ms. In five cell pairs, critical G(C) with 4-aminopyridine (4-AP) was reduced to 0.4 +/- 0.1 nS at a CL of 1,000 ms (P < 0.05 compared with control solution), and critical G(C) in 4-AP was unchanged by decreasing CL to 400 ms. It is possible that the "remodeling" of atrial cells due to atrial fibrillation or tachycardia, which has been shown to produce a decrease in the transient outward current, may result in an enhanced ability to propagate, possibly facilitating further development of fibrillation under conditions of decreased cellular coupling.

Action Potentials↗