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Biomedical subjects

S Rosen

Publications and source records attributed to S Rosen.

At least 73 records · Page 4Linked to original sources
PubMed1998

Goal-directed transesophageal echocardiography performed by intensivists to assess left ventricular function: comparison with pulmonary artery catheterization.

OBJECTIVES: Transesophageal echocardiography (TEE) is a valuable procedure for assessing left ventricular (LV) function, but it has not been widely applied in critical care because of the limited number of intensivists who are trained in echocardiography. This prospective study was designed to evaluate the feasibility of training intensivists to perform a goal-directed, limited-scope TEE to assess LV function in critically ill patients using a pediatric monoplane TEE probe. A secondary goal was to compare the usefulness of the TEE data with that of data obtained by a simultaneous pulmonary artery catheter (PAC). DESIGN: Prospective, blinded. SETTING: University teaching hospital. PARTICIPANTS: One hundred consecutive, intubated, intensive care unit patients. INTERVENTIONS: Five surgical intensivists with no previous background in echocardiography were trained under the supervision of two cardiologists to perform limited-scope TEE using a monoplane pediatric probe. One intensivist (A) reviewed the PAC data and recorded a diagnostic impression and therapeutic plan. A second intensivist (B), blinded to the PAC data, then performed TEE to determine cardiac volume, LV wall thickness, and LV global and regional wall motion. Intensivists A and B reviewed the data from both PAC and TEE, and intensivist A then formulated a new diagnosis and therapeutic plan. MEASUREMENTS AND MAIN RESULTS: Intensivists performed 48 TEE examinations under direct supervision of a cardiologist, and 52 without supervision, but reviewed poststudy. The average duration of TEE was 12 +/- 7 minutes. The intensivists' interpretations of TEE data were deemed correct in 93% of cases for LV wall thickness, 87% for intracardiac volume status, 81% for regional LV wall motion abnormalities, and 77% for global LV function. When the TEE and PAC technologies were compared, it was found that the TEE data disagreed with the PAC evaluation of intracardiac volume in 55% of cases and with the PAC assessment of myocardial function in 39% of cases. The post-PAC therapeutic recommendations were different from the post-TEE therapeutic recommendations in 58% of patients. CONCLUSIONS: Training intensivists in limited-scope, goal-directed TEE, using a pediatric monoplane probe to evaluate LV function, can be done rapidly and safely, and yield data pertinent to management of critically ill patients even in the early stages of skill acquisition.

Adult↗
PubMed1998

Interleukin-1 alpha increases the preferential cytotoxicity of an interleukin-2-diphtheria toxin fusion protein against neoplastic lymphocytes from patients with the Sezary syndrome compared to normal lymphocytes.

DAB389IL-2 is a recombinant fusion toxin composed of the diphtheria A chain and a protion of the translocating region of the diphtheria B chain, replacing the receptor binding domain with human IL-2. DAB389IL-2 can be safely administered to humans with mycosis fungoides (MF) or Sezary syndrome (SS), and antineoplastic effects occur. This agent binds optimally to the high-affinity IL-2R. The decreased efficiency of uptake by neoplastic cells which do not express the high-affinity IL-2R represents a potential limitation. Treatment of the HUT-78 cutaneous T-cell lymphoma with IL-1 alpha preceding exposure to DAB389IL-2 overcame their resistance to the toxin, IL-1 alpha inducing high-affinity IL-2R expression. Similarly, pretreatment with IL-1 alpha of SS patient lymphocytes demonstrated increased cytotoxicity compared to treatment with the fusion toxin alone. Normal lymphocytes and monocytes were not sensitive to DAB389IL-2 when pretreated with IL-1 alpha, suggesting a differential sensitivity which may be exploited clinically in the treatment of lymphomas.

Cell Line↗
PubMed1998

T cell-depleted autologous hematopoietic stem cell transplantation for multiple sclerosis: report on the first three patients.

Multiple sclerosis (MS) is a disease of the central nervous system characterized by immune-mediated destruction of myelin. In patients with progressive deterioration, we have intensified immunosuppression to the point of myeloablation. Subsequently, a new hematopoietic and immune system is generated by infusion of CD34-positive hematopoietic stem cells (HSC). Three patients with clinical MS and a decline of their Kurtzke extended disability status scale (EDSS) by 1.5 points over the 12 months preceding enrollment and a Kurtzke EDSS of 8.0 at the time of enrollment were treated with hematopoietic stem cell (HSC) transplantation using a myeloablative conditioning regimen of cyclophosphamide (120 mg/kg), methylprednisolone (4 g) and total body irradiation (1200 cGy). Reconstitution of hematopoiesis was achieved with CD34-enriched stem cells. The average time of follow-up is 8 months (range 6-10 months). Despite withdrawal of all immunosuppressive medications, functional improvements have occurred in all three patients. We conclude that T cell-depleted hematopoietic stem cell transplantation can be performed safely in patients with severe and debilitating multiple sclerosis. Stem cell transplantation has resulted in modest neurologic improvements for the first time since onset of progressive disease although no significant changes in EDSS or NRS scales are evident at this time.

Adult↗
PubMed1998

IgG antineutrophil cytoplasmic antibodies in IgA nephropathy: a clinical variant?

Anti-neutrophil cytoplasmic antibodies (ANCAs) of the immunoglobulin (Ig) G isotype are associated with rapidly progressive glomerulonephritis. These have been detected rarely in patients with Henoch-Schönlein purpura (HSP) and have only been previously reported once in a patient with IgA nephropathy (IgAN). In contrast, IgA-ANCAs have been detected in patients with HSP or IgAN, although further verification of this finding by various investigators has yielded conflicting results. We report a case of biopsy-proven IgAN in which the patient developed a rapidly progressive glomerulonephritis and was determined to have ANCAs of both IgA and IgG isotypes. This report suggests an association between fulminant IgAN and ANCA-associated disease and that ANCAs may be underdetected in children with previously diagnosed IgAN. Identification of these antibodies may guide further management of these patients.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1998

Ciprofloxacin overdose: acute renal failure with prominent apoptotic changes.

Acute renal failure due to ciprofloxacin has been well described. The previously reported cases have been consistent both clinically and pathologically with tubulointerstitial nephritis (TIN). We report a case of ciprofloxacin overdose leading to acute renal failure characterized by acute tubular necrosis (ATN). The outstanding features in the patient's renal biopsy were those of distal nephron apoptosis, best seen in plastic-embedded sections and electron microscopy. This report shows that the distal nephron can be singularly involved in acute renal failure and that electron microscopy or plastic-embedded sections may be necessary to define its involvement.

Acute Kidney Injury↗
PubMed1998

Auditory filter nonlinearity at 2 kHz in normal hearing listeners.

Auditory filters broaden with increasing level. Using a recently developed method of fitting filter shapes to notched-noise masking data that explicitly models the nonlinear changes in filter shape across level, results at 2 kHz from 9 listeners over a wide range of levels and notch widths are reported. Families of roex(p,w,t) filter shapes lead to models which account well for the observed data. The primary effect of level is a broadening in the tails of the filter as level increases. In all cases, models with filter parameters depending on probe level fit the data much better than masker-dependent models. Thus auditory filter shapes appear to be controlled by their output, not by their input. Notched-noise tests, if performed at a single level, should use a fixed probe level. Filter shapes derived in this way, and normalized to have equal tail gain, are highly reminiscent of measurements made directly on the basilar membrane, including the degree of compression evidenced in the input-output function.

Auditory Perception↗
PubMed1998

A non-cannabinoid immunogen used to elicit antibodies with broad cross-reactivity to cannabinoid metabolites.

A benzpyran derivative was linked to the lysines of bovine thyroglobulin (BTG) where 69% of the available lysines were modified. This derivative was designed to elicit antibodies that were directed towards the conserved epitopes of cannabinoid metabolites that appear in urine. Polyclonal antibodies from sheep and goats and murine monoclonal antibodies were generated using this immunogen. The cross-reactivity of the antibodies was compared with antibodies generated from the more traditional phenolic-linked or 9-linked immunogens. An ELISA assay was developed using delta 9-11-nor-9-carboxy-tetrahydrocannabinol (COOH-THC) to obtain a standard curve. The antibodies generated using the benzpyran immunogen showed an average of two to three times higher cross-reactivity towards 11-OH-delta 9-THC, 8 beta-OH-delta 9-THC, 8 alpha-OH-delta 9-THC, 11-OH-delta 8-THC, and 8 beta,11-di-OH-delta 9-THC than antibodies that were generated by traditional cannabinoid immunogens. The selectivity of the benzpyran-elicited antibodies was also compared with antibodies derived from traditional immunogens using clinical urine samples that were confirmed for cannabinoids by GC/MS. The total cross-reactive cannabinoid values obtained with the benzpyran-elicited antibodies were 49% higher than the values obtained using the traditional immunogen structures. The benzpyran immunogen-induced antibodies exhibited the same low cross-reactivity for non-structurally related compounds as antibodies derived from traditional immunogens. The novel benzpyran immunogen used in this study is the first non-cannabinoid immunogen used to generate cannabinoid-selective antibodies and demonstrates the usefulness of such a structure in developing broadly cross-reactive cannabinoid antibodies.

Animals↗
PubMed1997

Cytochrome c-dependent and -independent induction of apoptosis in multiple myeloma cells.

Cytochrome c is a mitochondrial protein that induces apoptosis when accumulated in the cytosol in response to diverse stress inducers. This protein has also been shown to cause apoptosis when added to cell free extracts. In this report, we studied the role of cytochrome c (cyto-c) in dexamethasone (Dex), anti-Fas monoclonal antibody (mAb), and ionizing radiation-induced apoptosis in multiple myeloma cells. The results demonstrate that ionizing radiation-induced apoptosis is associated with an increase in cytosolic cyto-c levels, whereas apoptosis induced by Dex or anti-Fas mAb has no detectable effect on cyto-c release. By contrast, caspase-3 was activated in response to all of these agents. Thus, our findings suggest that Dex or anti-Fas mAb-induced apoptosis is not accompanied by cyto-c release and that there are at least two different pathways leading to activation of caspases and induction of apoptosis in multiple myeloma cells that can be distinguished by accumulation of cytosolic cyto-c.

Apoptosis↗
PubMed1997

Indinavir nephropathy.

Explore the source record for details and available documents.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Association of diabetic retinopathy, ischemic heart disease, and albuminuria with diabetic treatment in type 2 diabetic patients. A population-based study.

The management of type 2 diabetes has been a controversial issue. The objective of the present study was to estimate patients' characteristics, particularly diabetes treatment, associated with retinopathy, coronary heart disease, and microalbuminuria in an unselected population of 532 type 2 diabetic individuals from three communities. Questionnaires, clinic record review, and physical examination were used for the assessment of the three conditions. Fasting C-peptide was measured in all insulin-treated participants to establish type 2 diabetes. Patients with and without each of the studied complications were matched for age at diagnosis of diabetes and duration of diabetes. Univariate matched and multivariate conditional logistic regression analyses were used to estimate the independent association between each of the various factors studied and the three complications. Insulin treatment was the only factor independently associated with all three complications (odds ratios 3.3, 3.4, and 5.3 for diabetic retinopathy, coronary heart disease, and albuminuria, respectively). Glycosylated hemoglobin, uric acid, systolic blood pressure levels, and body mass index were also independently associated with at least one of the complications but not with all of them. Although no cause-effect relationship can be established from this cross-sectional design, insulin therapy seems to be a marker of severer diabetes from the time of diagnosis.

Aged↗
PubMed1997

Renal microcirculation and tissue damage during acute ureteral obstruction in the rat: effect of saline infusion, indomethacin and radiocontrast.

Radiocontrast agents and nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used for the diagnosis and treatment of renal colic. We studied their impact during unilateral acute urinary outflow obstruction upon renal microcirculation and parenchymal integrity. Laser-Doppler and ultrasonic regional flow measurements demonstrated selective decline of outer medullary blood flow by 23 +/- 2% during an acute increase of intra-pelvic pressure to 50 to 55 cm H2O (N = 28, X +/- SEM, P < 0.01). In rats preconditioned with indomethacin, this manipulation reduced medullary blood flow by 50 +/- 4% (N = 16, P < 0.01 vs. obstruction alone), with cortical and total renal blood flow declining by 18 +/- 4% and 16 +/- 2%, respectively (P < 0.01). Unilateral obstruction alone for 24 hours in intact rats resulted in injury (hemorrhage and necrosis) to the papilla and fornix (formed laterally by inner stripe and medially by the inner medulla). These changes were detected as early as 30 minutes after ureteral ligature by staining for fragmented nuclear DNA (TUNEL). Mild damage of thick ascending limbs (mTALs) was associated with substantial medial fornix injury. Indomethacin markedly increased mTAL injury in obstructed kidneys, but attenuated inner medullary damage, both in the medial border of the urinary space and at the papilla. This latter protective effect, probably mediated by the decrease in intrapelvic pressure, was blunted by concomitant intravenous fluid load. Contrast media (iothalamate) and L-NAME (N omega nitro-L-arginine methyl ester) both augmented inner stripe and inner medullary damage in hydronephrotic kidneys. In rats concomitantly subjected to radiocontrast, indomethacin and L-NAME (an acute renal failure protocol, J Clin Invest 94:1069, 1994), unilateral obstruction augmented inner stripe hypoxic damage (65 +/- 6% vs. 24 +/- 11% of mTALs in contralateral kidneys, N = 7, P < 0.01). Injury was maximal at the fornix (93 +/- 6% vs. 39 +/- 14% of mTALs in the mid-inner stripe, P < 0.01) and extended to the outer stripe and medullary rays. Thus, in the rat acute ureteral obstruction alters medullary blood flow and within 24 hours produces medullary damage in both forniceal and inner medullary locations, that is exacerbated by concomitant measures which limit medullary oxygenation. Contrast studies, forced hydration and NSAIDs for renal colic are potentially harmful and their use should be re-evaluated.

Acute Disease↗
PubMed1997

Medullary injury in the ageing rat kidney: functional-morphometric correlations.

Urinary concentrating ability decreases with age in both humans and animals. This phenomenon is not yet clearly explained or corroborated by morphological findings, often focused on glomerular changes. In rats aged 5-22 months, semi-quantitative and quantitative morphometric analysis was performed to score cortical and medullary changes. Morphological-data were related to renal functional parameters. Three stages of tubulo-interstitial injury were observed: minimal findings (stage I); mild fibrosis with atrophy and casts in medullary thick ascending limbs (stage II): extensive fibrosis and atrophy with large cast formation (stage III). Maximal urinary osmolality decreased in correlation with the stage of tubulointerstitial injury (r = -0.8, P < 0.001), from 3735 mosmol L-1 at stage I to 2807 at stage II and 1567 at stage III. A dissociation was observed in the rate of progression with age between tubulointerstitial injury and glomerular sclerosis. Whereas sclerosis was observed in only 2-3% of glomeruli at both stages I and II of tubulointerstitial injury, damage to thick ascending limbs significantly increased from 2% of tubules at stage 1 to 11% at stage II (P < 0.002). At stage III, both extensive glomerular sclerosis (53%) and tubular injury (32%) were present. Uninephrectomy accelerated both morphological injury and functional compromise. We conclude that, in the early stages of renal ageing, injury to medullary tubules may be more prevalent than injury to glomeruli and could be responsible for the reduction in concentrating ability.

Aging↗
PubMed1997

An apparent flea-allergy dermatitis in kids and lambs.

Heavy infestation of lambs in two herds and kids in one herd with the cat flea, Ctenocephalides felis felis, accompanied by severe anaemia, eosinophilia and exudative dermatitis, is described. Flea infestation was more widespread during the summer months, when optimal climatic conditions for flea development prevail. The clinical and histological findings are discussed in the light of the pertinent literature. Recovery of the affected animals and normalization of the haematological values were observed after the insecticide treatment. Flea-allergic dermatitis is apparently the cause of the skin lesions in the lambs and kids.

Anemia↗
PubMed1997

Shiga toxin induces medullary tubular injury in isolated perfused rat kidneys.

To investigate the potential direct nephrotoxicity of Shiga toxin, a putative mediator for hemolytic uremic syndrome, purified toxin (10(-11) M) was added to isolated rat kidneys perfused for 160 min with a Krebs-Henseleit acellular medium enriched with albumin and amino acids. Kidney function and morphology were examined after perfusion with the Shiga toxin vs controls. Shiga toxin did not significantly alter renal perfusion flow, glomerular filtration rate, or tubular sodium reabsorption, but it significantly increased urinary protein excretion (from 61 +/- 23 to 169 +/- 28 microg/min, P < 0.01). On renal morphologic study, Shiga toxin did not induce gross glomerular damage but increased markedly the injury to the medullary thick ascending limbs. In conclusion, Shiga toxin is toxic to rat kidneys ex vivo and in the absence of platelets. Renal damage is manifested by proteinuria and medullary tubular injury. The distribution of this injury suggests a possible synergism between local medullary hypoxia and the toxic tubular or endothelial effects of the toxin. These effects may play a pathogenic role in the tubulo-interstitial injury observed in hemolytic uremic syndrome associated with severe renal failure.

Animals↗