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Biomedical subjects

R Shah

Publications and source records attributed to R Shah.

At least 91 records · Page 5Linked to original sources

Ventilator-associated pneumonia in patients with adult respiratory distress syndrome: CT evaluation.

PURPOSE: To determine the diagnostic accuracy of computed tomography (CT) for pneumonia in patients with adult respiratory distress syndrome (ARDS). MATERIALS AND METHODS: CT scans were obtained within 1 week of bronchoscopic sampling in 31 patients receiving mechanical ventilation for ARDS for more than 48 hours. Of 11 patients with pneumonia, five developed symptoms less than 11 days after the onset of ARDS (early ARDS). CT scans were rated for pneumonia independently by four radiologists who were unaware of the clinical diagnosis. Diagnostic accuracy was defined by means of the area under the receiver operating characteristic curve, or A2. RESULTS: Diagnostic accuracy for pneumonia was fair (A2 = 0.69 +/- 0.04 [standard error]) owing to 70% true-negative ratings (vs 59% true-positive ratings). The generalizability coefficient was good (0.79). No single CT finding was significantly different for the presence of pneumonia. Nondependent opacities predominated in 10 (91%) of 11 patients with pneumonia and 12 (60%) of 20 without pneumonia. Nondependent opacities predominated in nine (56%) of 16 patients with early ARDS and 13 (87%) of 15 with late ARDS. CONCLUSION: CT has fair diagnostic accuracy for ventilator-associated pneumonia in patients with ARDS owing primarily to identification of patients without pneumonia. No single CT sign was significantly different for pneumonia, but dependent atelectasis was more common in patients with early ARDS without pneumonia.

Adolescent↗

Dietary monounsaturated fatty acids promote aortic atherosclerosis in LDL receptor-null, human ApoB100-overexpressing transgenic mice.

In mice with genetically engineered high levels of plasma low density lipoprotein (LDL), we tested the hypothesis that an increase in the dietary content of monounsaturated fatty acids but not of polyunsaturated fatty acids would promote atherosclerosis. The mouse model used was an LDL receptor-null, human apoB100-overexpressing strain. Six experimental groups of 19 to 38 mice of both sexes were established when the animals had reached 8 weeks of age. For the next 16 weeks, individual groups were fed either a commercial diet or prepared diets including fat as 10% of energy, with 5 different fatty acid enrichment patterns including the following: saturated (sat), cis and trans monounsaturated (mono), and n-3 and n-6 polyunsaturated (poly). Highly significant differences (ANOVA, P<0. 0001) in LDL cholesterol (in mg/dL) were found, with the rank order at 16 weeks being trans mono (mean, 1390)>sat (922)=cis mono (869)=n-6 poly (868)>n-3 poly (652)>commercial diet (526). Significant elevations in very low density lipoprotein cholesterol were also found in the trans and cis mono and sat groups, and triacylglycerol concentrations were also elevated in all groups. High density lipoprotein cholesterol concentrations were consistently low (20 to 50 mg/dL) in all groups. Highly significant differences (ANOVA, P<0.0001) in atherosclerosis, quantified by measurement of aortic cholesteryl ester concentration (mg/g protein) among dietary fatty acid groups were found, with the order being trans mono (mean, 50.4)>sat (35.6)=cis mono (34.6)>n-6 poly (18. 3)=n-3 poly (9.7)=commercial diet (7.8). Therefore, in this mouse model of hypercholesterolemia, dietary cis or trans monounsaturated fat did not protect against atherosclerosis development, whereas aortic atherosclerosis in either of the polyunsaturated fat groups was significantly less than in the saturated fat group.

Analysis of Variance↗

Changes in the epidemiologic profile of sudden infant death syndrome as rates decline among California infants: 1990-1995.

OBJECTIVES: To evaluate changes in the rates and epidemiologic patterns of sudden infant death syndrome (SIDS) after implementation of public health campaigns to promote back sleeping and reduce exposure to cigarette smoke and environmental risk factors for SIDS. METHODS: California vital statistics data were used to evaluate changes in SIDS rates (deaths/1000 live births) and in the proportions of SIDS deaths by age and season of occurrence for California infants of black or other races from 1990 through 1995. RESULTS: From 1990 through 1995, 3508 SIDS deaths occurred. SIDS rates declined from 2.69 to 2.15 for black infants and from 1.04 to 0.61 for others between 1990 and 1995. Most SIDS deaths occurred during the 2nd to 4th months of life; the proportion of SIDS deaths during this period was unchanged for blacks but decreased for others from 70% to 65%. Of all SIDS deaths, 62% occurred during the colder season (October through March); the proportion of deaths in each season did not change for either race. CONCLUSION: California SIDS rates declined 20% for blacks and 41% for others between 1990 and 1995. Declines coincided with campaigns to reduce environmental risk factors for SIDS. Blacks continue to be at increased risk for SIDS compared with others, and the SIDS rate for blacks relative to others has increased. Reductions in SIDS mortality coinciding with interventions were smaller for blacks than for others. New strategies are needed to reduce further SIDS rates and narrow the gap between blacks and others.

Black or African American↗

Serum interleukin-6 levels in metastatic renal cell carcinoma before treatment with interleukin-2 correlates with paraneoplastic syndromes but not patient survival.

PURPOSE: We sought to determine the frequency of interleukin-6 (IL-6) expression in renal cancer cell lines, the frequency of the detection of IL-6 in the serum of patients with metastatic renal cell carcinoma, whether serum IL-6 level correlates with the development of paraneoplastic syndromes and whether serum IL-6 level in patients with metastatic renal cancer correlates with response to treatment with interleukin-2 (IL-2) or patient survival. MATERIALS AND METHODS: Conditioned media from 21 cell lines from 20 patients were examined for IL-6. We identified 2 matched groups of patients with metastatic renal cancer (30 responders and 29 nonresponders) to IL-2 based immunotherapy. Stored pretreatment serum specimens were evaluated for IL-6. Medical records were reviewed to determine the presence of paraneoplastic syndromes. RESULTS: IL-6 was detected in 19 of 21 renal cancer cell lines (90%) obtained from 20 patients with metastatic renal cancer as well as in the serum of 33 of 59 patients (56%) with metastatic renal cell carcinoma. A significant association between serum IL-6 level and anemia (p = 0.0032), elevated platelet count (p = 0.01), decreased albumin (p = 0.034) and elevated alkaline phosphatase (p = 0.04) was found. A trend was noted of the association of increased serum IL-6 level and fever (p = 0.051). No correlation was found between pretreatment serum IL-6 level and survival or response to IL-2. CONCLUSIONS: IL-6 was frequently secreted by renal cancer cell lines but it was only present in the serum of approximately half of the patients with metastatic renal cancer. Elevations of serum IL-6 were associated with paraneoplastic manifestations frequently seen in patients with renal cancer, including anemia, thrombocytosis, decreased albumin and elevations of alkaline phosphatase (Stauffer's syndrome). A weak relationship was noted between serum IL-6 level and fever but none was noted between that and survival or response to IL-2.

Adult↗

Lung volume reduction surgery for emphysema. A review.

Lung volume reduction surgery is emerging as a promising treatment option for selected patients with severe, debilitating end-stage emphysema refractory to medical management. Lung volume reduction surgery involves the removal of space occupying severely diseased, slowly ventilating and hyperexpanded lung, thus allowing the better conserved adjoining lung parenchyma to expand into the vacated space and function effectively. The operation can be accomplished by unilateral or bilateral thoracoscopy, thoracotomy or median sternotomy. The most emphysematous areas are excised using stapling or laser techniques or both. This review summarises the results of lung volume reduction surgery performed by various operative techniques. Results indicate that in the majority of patients improvement occurs in subjective dyspnoea and objective pulmonary function while oxygen and steroid dependence are reduced or eliminated at the cost of acceptable mortality and morbidity. Even though bilateral procedures produced much greater improvement, it is emphasized that it is the lung resection and not the operative approach that is critical to the success of the operation. Regardless of the technique used, the surgical treatment of emphysema is palliative in nature.

Endoscopy↗

Hepatic origin of cholesteryl oleate in coronary artery atherosclerosis in African green monkeys. Enrichment by dietary monounsaturated fat.

Relationships among plasma lipoprotein cholesterol, cholesterol secretion by the isolated, perfused liver, and coronary artery atherosclerosis were examined in African green monkeys fed diets containing cholesterol and 35% of calories as fat enriched in polyunsaturated, monounsaturated, or saturated fatty acids. The livers of animals fed monounsaturated fat had significantly higher cholesteryl ester concentrations (8.5 mg/g wet wt) than the livers of the other diet groups (3.65 and 3.37 mg/g wet wt for saturated and polyunsaturated fat groups, respectively) and this concentration was highly correlated with plasma cholesterol and apoB concentrations in each diet group. Cholesteryl oleate was 58 and 74. 5% of the liver cholesteryl ester in the saturated and monounsaturated fat groups. In each diet group, perfusate cholesteryl ester accumulation rate was highly correlated to liver and plasma cholesterol concentrations, and to plasma LDL cholesteryl ester content. Cholesteryl oleate was 48 and 67% of the cholesteryl esters that accumulated in perfusate in the saturated and monounsaturated fat animals, and this percentage was very highly correlated (r = -0.9) with plasma apoB concentration. Finally, in these two diet groups, liver perfusate cholesteryl ester accumulation rate was well correlated (r >/= 0.8) to coronary artery cholesteryl ester concentration, a measure of the extent of coronary artery atherosclerosis that occurred over the five years of diet induction in these animals. These data define an important role for the liver in the cholesteryl oleate enrichment of the plasma lipoproteins in the saturated and monounsaturated fat groups, and demonstrate strong relationships among hepatic cholesteryl ester concentration, cholesteryl ester secretion, and LDL particle cholesteryl ester content. The high correlation between liver cholesteryl ester secretion and coronary artery atherosclerosis provides the first direct demonstration of the high degree of importance of hepatic cholesteryl ester secretion in the development of this disease process. The remarkable degree of enrichment of cholesteryl oleate in plasma cholesteryl esters of the monounsaturated fat group may account for the relatively high amount of coronary artery atherosclerosis in this group.

Analysis of Variance↗

Immunotoxicological effects of benzene inhalation in male Sprague-Dawley rats.

The inhalation of benzene is toxic to various components of the immunologic system in rodents. Spleen and thymus weights, total spleen and femur marrow cell counts, enumeration of spleen B- and T-lymphocytes, and an assessment of humoral immunocompetence, were used to evaluate the immunotoxicity of benzene in male Sprague-Dawley rats. Rats were exposed to 0, 30, 200 or 400 ppm benzene for 6 h/day, 5 days/week for 2 or 4 weeks. An early indicator of immunotoxicity was a reduction in the number of B-lymphocytes after 2 weeks of 400 ppm. After 4 weeks of 400 ppm, there was a reduction in thymus weight and spleen B-, CD4+/CD5+ and CD5+ T-lymphocytes. Rats exposed to 30, 200 or 400 ppm benzene for 2 or 4 weeks and challenged with sheep red blood cells developed a humoral response comparable to that of the control (0 ppm) animals. Enumeration of spleen T- and B-lymphocytes in rats exposed to benzene and challenged with SRBC showed only a transient reduction in spleen B-lymphocytes after 2 weeks of exposure to 400 ppm. These data suggest that there are no immunotoxicological effects of exposure to 200 ppm benzene or less, in rats exposed for 6 h/day, 5 days/week for 2 or 4 weeks.

Administration, Inhalation↗

Effects of benzene on splenic, thymic, and femoral lymphocytes in mice.

Chronic exposure to high concentrations of benzene, primarily by inhalation, can affect the function of the human immune system. Limited data are available on the immunotoxic effects of low concentrations of benzene. This study evaluated the effects of 1, 5, 10, 100, and 200 ppm benzene on lymphocytes in mice exposed by inhalation for up to 8 weeks. Exposure to 100 or 200 ppm benzene induced rapid and persistent reductions in femoral B-, splenic T- and B-, and thymic T-lymphocytes. The percentage of femoral B-lymphocytes and thymic T-lymphocytes in apoptosis was increased 6- to 15-fold by 200 ppm benzene compared to controls. Replication of femoral B-lymphocytes was increased during the exposure period in the bone marrow as a compensation for the lymphocyte loss induced by 100 and 200 ppm benzene. Exposure of mice to 10 ppm benzene or less did not have a statistically significant effect on numbers or replication of the lymphocyte populations evaluated. A reduced number of splenic B-lymphocytes after 2 weeks of exposure to benzene appeared to be the most sensitive end point and time point for evaluating benzene cytotoxicity in this study.

Administration, Inhalation↗

The RuvC protein dimer resolves Holliday junctions by a dual incision mechanism that involves base-specific contacts.

The Escherichia coli RuvC protein resolves DNA intermediates produced during genetic recombination. In vitro, RuvC binds specifically to Holliday junctions and resolves them by the introduction of nicks into two strands of like polarity. In contrast to junction recognition, which occurs without regard for DNA sequence, resolution occurs preferentially at sequences that exhibit the consensus 5'-(A/T)TT/(G/C)-3' (where / indicates the site of incision). Synthetic Holliday junctions containing modified cleavage sequences have been used to investigate the mechanism of cleavage. The results indicate that specific DNA sequences are required for the correct docking of DNA into the two active sites of the RuvC dimer. In addition, using chemically modified oligonucleotides to introduce a hydrolysis-resistant 3'-S-phosphorothiolate linkage at the cleavage site, it was found that, as long as the sequence requirements are fulfilled, the two incisions could be uncoupled from each other. These results indicate that RuvC protein resolves Holliday junctions by a mechanism similar to that exhibited by certain restriction enzymes.

Bacterial Proteins↗

Genotoxicity and cytotoxicity in male B6C3F1 mice following exposure to mixtures of 1,3-butadiene and styrene.

1,3-Butadiene and styrene are oxidized, in part, by cytochrome P450 2E1 and have been shown to metabolically interact in rodents exposed by inhalation to mixtures of both compounds. Because the reactive metabolites of butadiene and styrene are thought to be responsible for the toxicity of each compound, metabolic interactions may alter the response in animals exposed to mixtures of butadiene and styrene compared with the response in animals exposed to butadiene alone or styrene alone. The purpose of this study was to quantitate alterations in genotoxicity and cytotoxicity in male B6C3F1 mice exposed to mixtures of butadiene and styrene. Male B6C3F1 mice were exposed to 6.25, 62.5, 200, or 625 ppm butadiene alone, 50 ppm styrene alone, or mixtures of 6.25, 62.5, 200, or 625 ppm butadiene and 50 ppm styrene. Genotoxicity was assessed by quantitating the frequency of micronucleated polychromatic erythrocytes in bone marrow. Cytotoxicity was assessed by counting total spleen and thymus cells and by quantitating the frequency of polychromatic erythrocytes in the peripheral blood. Butadiene and mixtures of butadiene and styrene were genotoxic in mice, as shown by a significant increase in the frequency of micronucleated polychromatic erythrocytes. The increased frequency following exposure to mixtures of butadiene and styrene was not significantly different compared with the frequency following exposure to butadiene alone. Styrene and mixtures of butadiene and styrene were cytotoxic in mice, as shown by significantly decreased number of spleen cells. Exposure to mixtures of butadiene and styrene with butadiene concentrations of 62.5 or 625 ppm significantly reduced the number of thymus cells. Exposure to 200 ppm or 625 ppm butadiene alone, or to mixtures of 200 ppm or 625 ppm butadiene and 50 ppm styrene, significantly reduced the frequency of polychromatic erythrocytes in the peripheral blood. The results of the study demonstrate that exposure to mixture of butadiene and styrene does not reduce the respective genotoxicity of butadiene or cytotoxicity of styrene.

Animals↗

A critical approach for longitudinal clinical trial of stretch PTFE aortic grafts.

Adaptation of new clinical products should be based upon thorough scientific evaluation of properties and performance in vitro and in vivo. Developmental animal research experimentation is classically carried out by the manufacturer with eventual government approval. However, objective data needs to be recorded during clinical trials including handling characteristics, bleeding, tensile strength, kinking, seamline break, dilatation, anastomotic deterioration, patency, and incorporation. Since April 1991, 1010 stretch polytetrafluoroethylene (PTFE) aortic grafts have been implanted at our institution and data were recorded prospectively. Six hundred and seven were for elective abdominal aortic aneurysms, 46 for symptomatic abdominal aortic aneurysms, 58 for ruptured abdominal aortic aneurysms, 17 for elective thoracoabdominal aneurysms, 3 for ruptured thoracoabdominal aneurysms and the remainder were for various aortoiliac pathology. Average age of the patients was 69 (range: 10-95), 66% were males, 25% were diabetics. Overall operative mortality was 5.8% (2.9% in elective cases and 26.6% in emergent cases). There were 23 occlusions; 21 were revised and 2 were replaced with axillofemoral bypasses. Estimated blood loss was 784 cc in elective cases and 1918 cc in emergent cases. Grafts were followed by duplex ultrasound or CT scan every 3 months during the first year and every 6 months thereafter. There were no graft dilatations or false aneurysms in this series. There was one graft infection and no perigraft seromas or anastomotic deteriorations during this follow up. Follow up was complete in 94% of these patients. In conclusion, stretch PTFE graft has acceptable handling characteristics, no excessive bleeding at the suture line and had no anastomotic or graft dilatation. This graft material was suitable for thoracic, visceral, renal and abdominal aortic reconstructions.

Adolescent↗

Surgical treatment of primary malignant chest wall tumours.

OBJECTIVE: Primary malignant tumours of the bony chest wall are uncommon and data concerning treatment and results are sparse. METHODS: To assess the results of surgical resection and chest wall reconstruction we reviewed our experience with primary malignant chest wall tumours treated since 1958. RESULTS: Of the 49 lesions, 42 were found in the ribs and the remaining 7 in the sternum. These included chondrosarcomas [22], solitary plasmacytoma [18], Ewing's tumours [7], Askin's tumour [1] and Desmoid tumour [1]. Skeletal reconstruction was performed in 36 of the 49 patients. Marlex mesh alone was used in 17 patients. Since 1972, a sandwich of two layers of Marlex mesh with a filler of methyl methacrylate was utilised [19] successfully, producing better functional and cosmetic results. Primary soft tissue closure was possible in all but 8 cases in whom latissimus dorsi myocutaneous flaps were used. Bilaterally, partially transposed pectoralis major muscle was used to cover upper sternal defects in 4 cases. All but 1 patient had an uneventful post-operative recovery none requiring ventilatory support. SURVIVAL: Overall survival at 5 and 10 years was 68%. The differential figures for 10-year survival were for chondrosarcoma 67%, Ewing's sarcoma 43%, and solitary plasmacytoma 59%. These were the results of radical en-bloc excisions. The patient with Desmoid tumour is alive at 5 years, following incomplete initial resection and the patient with Askin's tumour survived for 3 years. CONCLUSION: Radical en-bloc excision remains the treatment of choice in all primary malignant chest wall neoplasms except large solitary plasmacytomas where incisional biopsy followed by irradiation appears to be the method of preference. In Ewing's and Askin's tumours, additional chemotherapy and radiotherapy have to be used. The extent of surgical excision should only be limited by the amount of tissue necessary to remove for adequate malignant tissue clearance, since even large defects can be reconstructed with little functional disturbance.

Adult↗

Improving services to Asian families and children with disabilities.

There is a clear need to improve the delivery of services to Asian families and their children with disabilities. This paper describes some of the key points where communication and access may break down. It offers principles to guide assessments of children, and makes recommendations on ways of working with interpreters, monitoring uptake of services and strategies for supporting and informing Asian families.

Asia↗

Excessive proliferation matched by excessive apoptosis in myelodysplastic syndromes: the cause-effect relationship.

The paradox of pancytopenia despite cellular bone marrows (BM) was investigated in 120 patients with myelodysplastic syndromes (MDS). Detailed cell cycle kinetics were examined following in vivo infusions of iodo--and/or bromodeoxyuridine (IUdR/BrdU), while the incidence of apoptosis was measured by in situ end labeling (ISEL) of fragmented DNA. Results showed that MDS are highly proliferative disorders with an equally high incidence of apoptotic intramedullary cell death accounting for the paradox of cellularity/cytopenia. By double-labeling BM biopsy sections for ISEL/BrdU we found the peculiar situation of "signal antonymy" where S-phase cells were frequently apoptotic, a phenomenon so far only seen in MDS biopsies. The cause-effect relationship of this excessive proliferation/apoptosis is discussed at length.

Apoptosis↗

Cell cycle kinetic studies in 68 patients with myelodysplastic syndromes following intravenous iodo- and/or bromodeoxyuridine.

Sixty-eight patients with myelodysplastic syndromes (MDS) received sequential infusions of iodo- and/or bromodeoxyuridine for cell kinetic analysis. Bone marrow biopsy sections were treated by appropriate antibodies and a labeling index (LI), duration of S-phase (Ts), and total cell cycle time (Tc) of myeloid cells were determined. The mean LI was 28.4%, Ts was 11.8 hours and Tc was 40.7 hours. The %LI decreased as the disease evolved from refractory anemia toward transformation to acute leukemia (p = 0.04). Double-labeling of biopsy sections for apoptosis and proliferation showed that 30-90% of S-phase cells in MDS patients were simultaneously apoptotic or "antonymous." We conclude that MDS are highly proliferative disorders in which the ineffective hematopoiesis is probably the result of excessive apoptosis rather than slow proliferation.

Apoptosis↗