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S Sharma

Publications and source records attributed to S Sharma.

At least 415 records · Page 23Linked to original sources

Abnormal cardiopulmonary exercise variables in asymptomatic relatives of patients with dilated cardiomyopathy who have left ventricular enlargement.

BACKGROUND: Left ventricular enlargement with normal systolic function is common in asymptomatic relatives of patients with familial dilated cardiomyopathy, many of whom progress to overt dilated cardiomyopathy at follow up. OBJECTIVE: To examine maximal and submaximal gas exchange variables of cardiopulmonary exercise testing in asymptomatic relatives with left ventricular enlargement. DESIGN AND SETTING: Controlled evaluation of metabolic exercise performance of patients with dilated cardiomyopathy and asymptomatic relatives with left ventricular enlargement identified through prospective family screening in a cardiomyopathy outpatient clinic. METHODS: 23 relatives with left ventricular enlargement, 33 normal controls, 29 patients with dilated cardiomyopathy, and 10 elite athletes with echocardiographic criteria of left ventricular enlargement ("physiological" enlargement) underwent symptom limited upright cycle ergometry using a ramp protocol. RESULTS: Peak oxygen consumption (pVO(2); mean (SD)) was significantly reduced in relatives with left ventricular enlargement (78 (16.3)%) v normal controls (96%, p < 0.01) and athletes (152%, p < 0.001), but was higher than in patients with dilated cardiomyopathy (69%, p < 0.01). pVO(2) was less than 80% of predicted in 75% of patients, 58% of relatives, 22% of controls, and none of the athletes. Oxygen pulse (pVO(2)/heart rate) was less than 80% of predicted in 69% of patients, 35% of relatives, 6% of controls, and none of the athletes. The slope of minute ventilation v CO(2) production (DeltaVE/DeltaVCO(2)) was > 30 in 68% of patients, 50% of relatives, and in none of the controls or athletes. Anaerobic threshold, occurring in relatives at 37 (14)% of the predicted VO(2), was higher than in the patients (32%, p < 0.01) and lower than in the controls (45%, p < 0.05) or in the athletes (55%, p < 0.001). CONCLUSIONS: Maximal and submaximal cardiopulmonary exercise test variables are abnormal in asymptomatic relatives with left ventricular enlargement, in spite of normal systolic function. This provides further evidence that left ventricular enlargement represents subclinical disease in relatives of patients with dilated cardiomyopathy. Metabolic exercise testing can complement echocardiography in identifying relatives at risk for the development of dilated cardiomyopathy.

Adolescent↗

Hypertrophic cardiomyopathy: the interrelation of disarray, fibrosis, and small vessel disease.

OBJECTIVE: To make a quantitative assessment of the relation between disarray, fibrosis, and small vessel disease in hypertrophic cardiomyopathy. DESIGN: Detailed macroscopic and histological examination at 19 segments of the left and right ventricle and the left atrial free wall. PATIENTS: 72 patients with hypertrophic cardiomyopathy who had suffered sudden death or progression to end stage cardiac failure (resulting in death or heart transplantation). MAIN OUTCOME MEASURES: The presence of scarring, atrial dilatation, and a mitral valve impact lesion were noted, and heart weight, wall thickness, per cent disarray, per cent fibrosis, and per cent small vessel disease quantitated for each heart. RESULTS: Within an individual heart the magnitude of hypertrophy correlated with the severity of fibrosis (p = 0.006) and disarray (p = 0.0002). Overall, however, total heart weight related weakly but significantly to fibrosis (r = 0.4, p = 0.0001) and small vessel disease (r = 0.3, p = 0.03), but not to disarray. Disarray was greater in hearts with mild left ventricular hypertrophy (maximum wall thickness < 20 mm) and preserved systolic function (60.9 (26)% v 43 (20.4)% respectively, p = 0.02) and hearts without a mitral valve impact lesion (26.3% v 18.9%, p = 0.04), but was uninfluenced by sex. Fibrosis was influenced by sex (7% in male patients and 4% in female, p = 0.04), but not by the presence of an impact lesion. No relation was found between disarray, fibrosis, and small vessel disease. CONCLUSIONS: Myocyte disarray is probably a direct response to functional or structural abnormalities of the mutated sarcomeric protein, while fibrosis and small vessel disease are secondary phenomena unrelated to disarray, but modified by factors such as left ventricular mass, sex, and perhaps local autocrine factors.

Adolescent↗

Disseminated fungal infection complicated with pulmonary haemorrhage in a case of acute myeloid leukaemia.

Pulmonary haemorrhage is a common necropsy finding in acute leukaemia, however, it is rarely diagnosed during life. A man with acute myeloid leukaemia is reported who presented with disseminated fungal infection, anaemia, thrombocytopenia, and subconjuctival and petechial haemorrhages. During the course of the patient's illness, the chest infection was complicated with bilateral pulmonary haemorrhage. The diagnosis of pulmonary haemorrhage was based on characteristic clinical and radiological findings. The patient improved on treatment.

Bronchoalveolar Lavage↗

Adenoviral gene transfer is inhibited by soluble factors in malignant pleural effusions.

Direct in vivo gene delivery is a prerequisite for many gene therapy strategies; however, efficacy has been limited by a lack of therapeutic gene transfer. In studying intrapleural malignancy as a model for the gene therapy of non-small cell lung cancer, we previously identified soluble chondroitin sulfate-proteoglycans/glycosaminoglycans (CS-PG/GAGs) in malignant pleural effusions (MPE) as factors that inhibit retroviral vector (RV) transduction. Similarly, we have observed inhibition to gene transfer in the fluid component of MPE using adenoviral (Ad) vectors. Analyses indicate that the factors responsible for the block are filterable, soluble, titrable, and heat stable (56 degrees C). Passage through microporous membranes fractionates the inhibitory factors into large (> 100 kD) components of the effusions. In contrast to RV transduction, hyaluronic acid or CS-PG/GAGs are not the inhibitors because the block is not reversed by pretreatment of the effusions with mammalian hyaluronidase, and exogenous addition of GAGs into the transduction media does not diminish Ad transduction. In considering the mechanism of action of the inhibitory factors, we observe that Ad entry, and specifically the binding of radiolabeled Ad to its target cell, is inhibited in the presence of MPE. Ad internalization may also be impaired; however, these studies exclude soluble fibronectin in MPE as a competitive inhibitor of Ad transduction. Lastly, sepharose A- mediated immunoglobulin depletion of MPE only partially reverses the block, and significant inhibition to Ad gene transfer persists at lower adenovirus:target cell ratios. Identifying the structural and functional basis for inhibition to Ad gene transfer may yield specific strategies to enable better in vivo translation of gene therapy approaches.

Adenoviridae↗

Non-fatal ethylene dibromide ingestion.

Ethylene dibromide (1,2-dibromoethane) is widely used to fumigate grain and fruit in India. However, acute poisoning due to it has rarely been reported in the literature and most of these patients had an fatal outcome. We describe the suicide attempt of a young male who ingested an ampoule (3 ml) of it, developed acute hepatic and renal failure, metabolic acidosis and coagulopathy but survived following supportive measures.

Acute Kidney Injury↗

Labor-associated changes in Fas ligand expression and function in human placenta.

Fas ligand (FasL)-dependent apoptosis has been implicated in the control of tissue-damaging inflammatory responses in several immune privileged sites. Here, we present data demonstrating that FasL is expressed on human trophoblast cells throughout pregnancy and transduces growth inhibitory/death signals in cells bearing its receptor, Fas (CD95). Immunohistochemical analysis detected FasL-positive staining in the trophoblast layer of villi of first- and second-trimester and term (no labor) placental tissues, as well as in freshly isolated cytotrophoblasts representing these gestational ages. In contrast, term placental tissues and cytotrophoblasts from labor-associated deliveries exhibited significantly reduced FasL expression, suggesting that parturition altered the characteristics of trophoblast cells. FasL-specific immunoblotting of cytotrophoblast cell lysates further confirmed these results. To assess the functionality of FasL expressed on cytotrophoblasts, we co-cultured these cells with Fas-bearing Jurkat T cells. Cytotrophoblasts from early pregnancy, or term with no labor, significantly inhibited growth in Jurkat cells, evident even at a 1:1 effector:target cell ratio, as determined by the incorporation of [3H]thymidine. Similar results were obtained when a FasL-positive colon carcinoma cell line, SW620, was used in place of cytotrophoblasts. In contrast, term cytotrophoblasts from labor deliveries exhibited poor FasL expression and were quantitatively much less proficient in inhibiting [3H]thymidine incorporation in Jurkat cells. These data indicate that FasL could participate in modulating the inflammatory responses associated with labor and suggest intrinsic molecular differences in the placental microenvironment before and after labor .

Base Sequence↗

Management of acute surgical orbital haemorrhage: an otorhinolaryngological and ophthalmological perspective.

This retrospective report describes the management and outcome of seven patients who suffered an acute surgical orbital haemorrhage (ASOH), secondary to a surgical procedure performed on either the sinuses, orbits or eyelids. All patients but one recovered their pre-operative vision. A management plan is outlined on how to assess and tackle this complication, so that the ENT surgeon may be better prepared to meet such an acute surgical emergency, should it arise.

Adult↗

Oral chemotherapeutic agents for colorectal cancer.

A number of novel oral chemotherapeutic agents are entering practice or are under development in the United States. Many of these agents display significant clinical activity against colorectal cancer. Many classes of compounds, including fluoropyrimidine analogs, dihydropyrimidine dehydrogenase (DPD) inhibitors, topoisomerase inhibitors, farnesyl transferase inhibitors, and others, are being developed for oral administration. This manuscript describes the progress of clinical development of these agents and also explores the relative merits and challenges of these approaches. Economic issues, patient preference, and patient selection issues surrounding oral chemotherapy for colorectal cancer will also be discussed.

Administration, Oral↗

Fatal cerebroembolism from nonbacterial thrombotic endocarditis in a trauma patient: case report and review.

Nonbacterial thrombotic endocarditis (NBTE) is a rare condition that may result in an unexpected and usually fatal cerebroembolism. It occurs in a variety of clinical situations, including malignancy, immune disorders, and sepsis, but it has rarely been reported after trauma. The formation of NBTE appears to require a hypercoagulable state and changes in valvular morphology, e.g., during a hyperdynamic state. Patients with disseminated intravascular coagulation have a 21% incidence of NBTE. Although NBTE is usually found at autopsy, premorbid detection by echocardiography is currently possible and feasible. Untreated patients have a high incidence of embolic events, but anticoagulation with heparin may be life-saving. A lethal case of NBTE in a severely injured patient is reported here with the purpose of increasing awareness among medical personnel caring for trauma patients. Recommendations have been made for surveillance echocardiography in high-risk patients, e.g., critically ill patients with sepsis or disseminated intravascular coagulation.

Adult↗

Analysis of costs.

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Choroid Neoplasms↗

Acute alcoholic myopathy, rhabdomyolysis and acute renal failure: a case report.

A case of middle aged male who developed swelling and weakness of muscles in the lower limbs following a heavy binge of alcohol is being reported. He had myoglobinuria and developed acute renal failure for which he was dialyzed. Acute alcoholic myopathy is not a well recognized condition and should be considered in any intoxicated patient who presents with muscle tenderness and weakness.

Acute Kidney Injury↗