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Biomedical subjects

S Shroff

Publications and source records attributed to S Shroff.

At least 19 recordsLinked to original sources
PubMed2025

HLA-E and NKG2A Mediate Resistance to BCG Immunotherapy in Non-Muscle-Invasive Bladder Cancer.

Bacillus Calmette-Guérin (BCG) is the first-line therapy for high-grade non-muscle-invasive bladder cancer (NMIBC), yet many patients experience recurrence due to immune evasion. We identify HLA-E and NKG2A as mediators of adaptive resistance involving chronic activation of NK and T cells in BCG-unresponsive tumors. Prolonged IFN-γ exposure enhances HLA-E and PD-L1 expression on recurrent tumors, accompanied by the accumulation of NKG2A+ NK and CD8 T cells. HLA-Ehigh tumor cells preferentially cluster near CXCL12-rich stromal regions with dense effector cell presence, underscoring a spatially segregated tumor architecture. Although cytotoxic lymphocytes retain effector potential, their activity is restrained by HLA-E/NKG2A and PD-L1/PD-1 pathways located in their immediate neighborhood within the bladder tumor microenvironment. These data reveal a spatially organized immune escape program that limits anti-tumor immunity. Our findings support dually targeting NKG2A and PD-L1 checkpoint blockade as a rational, bladder-sparing strategy for patients with BCG-unresponsive NMIBC.

BCG-unresponsive↗
PubMed1999

Modified technique of suction blistering for epidermal grafting in vitiligo.

BACKGROUND: Suction blister epidermal grafting is a useful modality of treatment of resistant and stable vitiligo; however, it requires expensive and heavy suction apparatus. This study is an attempt to develop a cheap and small apparatus which can be assembled in the physician's own office. PATIENTS AND METHODS: The method was tried in 22 vitiligo/leukoderma patients. The apparatus consisted of a cylindrical funnel connected with a three-way tap, and suction was given by a 50-mL syringe. The pressure inside the suction cup was retained by changing the position of lock of the three-way tap. The pressure was measured by connecting the three-way tap to a vacuum gauge. The apparatus remained adhered to the donor area because of negative pressure. The blister was formed in about 1.5 h. The roof of the blister was grafted onto the dermabraded recipient site. RESULTS: The pigmentation was complete in 20 out of 22 patients. There were no complications. CONCLUSIONS: The technique is inexpensive and easy and obviates the need of cumbersome and heavy equipment.

Adolescent↗
PubMed1998

Renal aspergillosis giving rise to obstructive uropathy and recurrent anuric renal failure.

A sixty-year-old previously healthy male patient presented with anuric renal failure of sudden onset. He was detected to have Aspergillus fumigatus fungal balls in the renal pelvis, ureters and bladder which were removed and his renal function improved. He was treated with itraconazole and sent home. Three weeks later he again presented with anuria and renal failure. He had recurrence of the obstruction with the same fungus. The fungal ball was removed, a double 'J' stenting was performed and he was treated with amphotericin B and itraconazole. Hence we report a previously healthy patient with no evidence of immunosuppression presenting an obstructive anuric renal failure due to isolated renal aspergillosis.

Acute Kidney Injury↗
PubMed1997

Proportionate reversible decreases in systolic function and myocardial oxygen consumption after modest reductions in coronary flow: hibernation versus stunning.

OBJECTIVES: This study sought to determine whether modest short-term reductions in coronary flow can produce subsequent proportionate reductions in myocardial function and O2 consumption compatible with myocardial hibernation. BACKGROUND: Acute studies indicate that myocardial energy utilization can be downregulated during moderate flow reduction. Whether this apparently beneficial adjustment persists into the reperfusion period is unsettled because most postischemic contractile dysfunction has been presumed to represent stunned or irreversibly injured myocardium. METHODS: Responses of regional myocardial function and O2 consumption were assessed in chronically instrumented dogs after approximately 50% reductions in flow for 2 h (n = 8) or repeated 2-min total coronary occlusions (n = 6). RESULTS: When unrestricted perfusion was restored after sustained partial occlusions, regional function and O2 consumption stabilized at proportionate, systematically decreased levels ([mean +/- SEM] 80 +/- 3.1% and 81 +/- 5.1% of control values, both p < 0.05) and then returned to control values within 24 h. Similar proportionate reductions occurred after as few as five cycles of brief total occlusion (79 +/- 5.1% and 83 +/- 1.6% of control values, both again p < 0.05); these persisted with additional occlusions and then returned to baseline values within 3 h. The absence of irreversible injury was documented histologically in both series. Sham animals (n = 5) showed no changes in regional function or O2 consumption throughout similar experimental periods. CONCLUSIONS: Moderate decreases in coronary flow or repeated brief coronary occlusions can be followed by proportionate reversible reductions in regional systolic function and O2 consumption compatible with the traditional definition of myocardial hibernation. These findings emphasize the complexity of myocardial responses to flow restriction and call attention to limitations in characterizing reversibly hypocontractile myocardium as simply hibernating or stunned.

Animals↗
PubMed1996

The holmium: YAG laser for ureteric stones.

OBJECTIVE: To assess the efficacy of the pulsed holmium: YAG laser for the fragmentation of ureteric stones. PATIENTS AND METHODS: One hundred patients (72 males and 28 females, age range 14 months-85 years) underwent 114 ureteroscopic procedures using either a 7.2 F semi-rigid or 9.5 F flexible ureteroscope. A holmium: YAG laser (Sunrise Technologies. Fremont, Ca, USA) was used for laser lithotripsy at a maximum energy of 1.0 J/pulse at 5 Hz. Most of the stones (46%) were located in the upper third of the ureter. The mean size of the stones was 9 x 8 mm and the mean duration of the procedure was 73 min (including anaesthesia) with a mean hospital stay of 2.7 days. RESULTS: All the stones were accessed successfully using miniaturized endoscopes either retrogradely or antegradely. The holmium laser effectively fragmented all types of stones. Total clearance of all stones fragments was achieved in 87% of cases, with the best results obtained for stones in the lower third of the ureter (96%). The complications attributed directly to the laser included three strictures and three perforations of the ureteric wall. CONCLUSION: The holmium: YAG laser was effective in fragmenting ureteric stones irrespective of their hardness. However, it has the potential to damage the ureteric wall and must be used with caution.

Adolescent↗
PubMed1995

Experience with ureteroscopy in children.

OBJECTIVE: To present our experience of ureteroscopic procedures in children using miniaturized instrumentation. PATIENTS AND METHODS: Fourteen children aged between 13 months and 14 years underwent 20 ureteroscopic procedures. Semi-rigid 7.2 F and flexible 9.5 F ureteroscopes were used in a retrograde and an antegrade fashion. Eighteen ureteroscopies were performed retrogradely and two antegradely. Of the 20 ureteroscopic procedures, 18 were for stone disease, one for haematuria of unknown origin and one for removal of a migrated stent. The average size of the stone was 12.9 x 6.6 mm. RESULTS: Access using miniaturized ureteroscopes was successful in all patients. Dilatation was required only in 1 of 20 procedures. The management of stone disease in 10 of 13 children was straightforward and a single ureteroscopy was required to clear the ureters. In three of 13 children with stone disease the problems were more complex and nine ureteroscopies were undertaken to render the ureters stone free. Complications were stricture at the site of stone impaction (one patient), retention of urine due to a stone fragment in the urethra (one patient), haematuria (one patient) and migrated stent requiring ureteroscopy (one patient). CONCLUSION: In the hands of an experienced surgeon ureteroscopy can be used with equal success in children as in adults to treat calculus disease.

Adolescent↗
PubMed1993

Ultrasonic backscatter system for automated on-line endocardial boundary detection: evaluation by ultrafast computed tomography.

OBJECTIVES: The purpose of this study was to evaluate the accuracy of the recently developed echocardiographic on-line endocardial border detection system using ultrafast computed tomography, an independent and proved tomographic imaging modality. BACKGROUND: The automated system for on-line endocardial border detection identifies the blood-tissue interface by acoustic quantification of the ultrasonic backscatter signal. METHODS: Eighteen subjects were screened by conventional echocardiography and acoustic quantification. Ten of these, with high quality echocardiographic images, were also examined by ultrafast computed tomography. Comparable image planes at the midpapillary level were analyzed. Measurements of left ventricular cavity area were compared at end-diastole and end-systole and time course analyses of cavity area during the cardiac cycle were performed. RESULTS: There was good correlation between values for left ventricular end-diastolic area (r = 0.99), end-systolic area (r = 0.93) and fractional area change (r = 0.91) using the two methods. The on-line backscatter system underestimated end-diastolic area (p < 0.001), but the negative bias was small (-1.6 cm2) and the 95% confidence intervals were narrow (-3.6 cm2 to +0.4 cm2). In contrast, the backscatter system overestimated end-systolic area (p < 0.02); the positive bias for this variable was also small (+2.6 cm2) but the confidence intervals were relatively wide (+7.9 to -2.8 cm2). The negative bias of backscatter values for cavity area was fairly constant during diastole and early systole (range -5% to -10%), but during the second half of systole, backscatter values increased progressively relative to computed tomographic values. Real time values for fractional area change measured by the backscatter system were 13% smaller than those determined by ultrafast computed tomography (p < 0.001), with wide confidence intervals (+3% to -30%). Absolute peak rates of area change during systole and diastole were lower by 39% (p < 0.001) and 41% (p < 0.01), respectively, using the on-line ultrasonic backscatter system. Time course analyses revealed the errors to be consistent with cardiac cycle-dependent alterations in gain sensitivity of the ultrasonic backscatter system. CONCLUSIONS: The ultrasonic backscatter system is associated with cyclic cavity area measurement errors that need to be addressed if its early promise for on-line assessment of ventricular function is to be fulfilled. Incorporation of an electrocardiographically triggered time-varying gain control may improve accuracy for on-line analysis of ventricular performance.

Echocardiography↗
PubMed1991

Arterial mechanical properties in dilated cardiomyopathy. Aging and the response to nitroprusside.

The effects of aging on arterial mechanical properties and the response to nitroprusside were examined in 25 patients with dilated cardiomyopathy. High-fidelity pressures were recorded with a multisensor catheter. Pulse wave velocity was determined between two sensors in the thoracic aorta. Arterial compliance was determined by an analysis of the diastolic waveform and cardiac output. At baseline, despite a similar systemic vascular resistance, the pulsatile load (e.g., arterial compliance) and wave transmission characteristics (e.g., pulse wave velocity) were altered with aging. Arterial compliance was reduced in older (greater than 50 yr, n = 8) versus younger (less than 35 yr, n = 8) patients (0.51 +/- 0.17 vs. 1.33 +/- 0.63 ml/mmHg, P less than 0.01) and intermediate in those 35-50 yr of age (n = 9, 0.72 +/- 0.40 ml/mmHg). There was a positive correlation between age and pulse wave velocity (r = +0.90). Nitroprusside infusion decreased resistance, increased arterial compliance, and lowered pulse wave velocity in all groups. Yet, advancing age was associated with a greater fall in wave velocity for a given fall in aortic pressure. The slope (K) of the relation between pulse wave velocity and aortic diastolic pressure progressively increased with age (0.01 +/- 0.03, 0.06 +/- 0.02, and 0.09 +/- 0.03 m/s-mmHg). Multiple linear regression analysis revealed a significant relation between K and age. These data demonstrate that in older patients with dilated cardiomyopathy the left ventricle is coupled to an arterial circulation that has a greater pulsatile load, despite a similar steady load. Furthermore, these age-related changes in the arterial system affect the hemodynamic response to pharmacologically-induced vasodilatation.

Adult↗
PubMed1987

Extracardiac pressure and ventricular haemodynamics.

To investigate the relative influence of pericardial and intrathoracic pressures on left and right ventricular diastolic and systolic pressures two experimental groups were studied: group 1-10 open chest dogs with a controlled pericardial effusion; and group 2 - five closed chest dogs with a controlled pneumothorax at constant transpulmonary pressure and lung volume. In both groups right and left ventricular diastolic pressures were linear functions of external pressure with respective slopes of 0.71 and 0.39 for group 1 and 0.80 and 0.78 for group 2. The left ventricular slope of 0.39 indicates that left ventricular volume decreased more with increments in pericardial pressure since a slope of approximately 1.00 would be expected if the filling volume was invariant. Accordingly, the fall in left ventricular systolic pressure that occurred in both groups was two to three times greater in group 1. Right ventricular systolic pressure fell in group 1 whereas it increased in group 2. It is concluded that there are no major differences between the influence of either type of external pressure on right ventricular filing. In contrast, the left ventricle, and in particular the filling pressure gradient between the pulmonary circulation and the left ventricle, is more sensitive to pericardial pressure.

Animals↗
PubMed1985

Characteristics of vascular hydraulic load in patients with heart failure.

Aortic input impedance and hydraulic power were derived from simultaneous catheter recordings of ascending aortic pressure and velocity in eight normal subjects and 11 age-matched subjects with clinical heart failure secondary to idiopathic congestive cardiomyopathy. Resting data revealed the characteristic depression of cardiac output and elevation of systemic vascular resistance in patients with heart failure. The pulsatile component of vascular hydraulic load, characteristic impedance (Zc), was similar in both groups (Zc normal: 85 +/- 30 dyne-sec-cm-5; Zc cardiomyopathy: 93 +/- 33 dyne-sec-cm-5). The oscillatory fraction of aortic input power in patients with heart failure (14 +/- 4%) was also similar to that of normal subjects (11 +/- 2%). The transition from rest to exercise in patients with heart failure was marked by a decrease in the steady component of arterial hydraulic load, although characteristic impedance did not change. A similar qualitative response occurred in normal subjects, although the systemic vascular resistance during exercise remained above normal in patients with heart failure. The modulus of the first harmonic of impedance significantly decreased during exercise in normal subjects but did not change significantly in patients with heart failure. Furthermore, the modulus of the first harmonic of the reflection coefficient decreased significantly during exercise in normal subjects but did not change in patients with heart failure in spite of systemic vasodilation. Exercise appears to impose no additional increase in vascular hydraulic load on the ejecting left ventricle. The similar aortic characteristic impedances in patients with heart failure and in normal subjects, at rest and during exercise, are consistent with a constant oscillatory fraction of input power.

Adult↗
PubMed1981

Contractile mechanics and interaction of the right and left ventricles.

The heart and lungs, together with hemoglobin, provide for the transport of oxygen from the atmosphere to the metabolizing tissue. The oxygenation of blood and the circulation of oxygenated blood are precisely synchronized so that the heart and lungs constitute an integrated cardiopulmonary unit. The functional integration of the heart and lungs is fostered by their anatomic arrangement and mechanical interaction. The cardiopulmonary unit consists of the right and left ventricles (two in-series pumps composed of cardiac muscle), which are mechanically coupled by the lungs. The factors that control cardiac muscle shortening (fiber length, afterload and myocardial contractile state) also regulate the pumping behavior of each ventricle. Because the ventricles are aligned in series a perturbation in the mechanical events of one ventricle will influence the behavior of the other ventricle. The interventricular septum and pericardium further promote the mechanical interplay between ventricles. Intrathoracic pressure (the pressure that surrounds the cardiopulmonary unit) creates an additional interaction between the ventricles as well as the heart and lungs.

Acute Disease↗