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Biomedical subjects

R Jaffe

Publications and source records attributed to R Jaffe.

At least 37 records · Page 2Linked to original sources
PubMed1999

Epstein-Barr virus-related disorders in children undergoing renal transplantation with tacrolimus-based immunosuppression.

In children undergoing renal transplantation, Epstein-Barr virus- (EBV) related disorders, including posttransplant lymphoproliferative disorder, constitute a major complication associated with tacrolimus-based immunosuppression. In this study, we reviewed the EBV complications in 81 children, all of whom had EBV serological studies before renal transplantation. We also highlight the data in a subgroup of 30 children transplanted more recently who were monitored sequentially for EBV symptoms and signs and with immunological studies, and in whom the donor EBV serology was also determined. During a mean follow-up time of 3.9+/-2.3 years, 19 children developed symptomatic Epstein-Barr virus (EBV*) infection. This consisted of the clinical syndrome of infectious mononucleosis in 7 children; in addition, 10 children developed posttransplant lymphoproliferative disorder (PTLD), which was histologically confirmed in 8, and 2 others developed malignant lymphoma. Recipient seronegativity (EBV-) and donor EBV seropositivity (EBV+) predicted a high probability for seroconversion (P=0.0072) and for developing PTLD or malignancy (P<0.01). In the subgroup of 30 children studied prospectively, seroconversion occurred in 15 of 19 seronegative recipients of EBV seropositive grafts at 6.6+/-2.6 months (mean+/-SD) after transplantation. Seven children developed symptomatic EBV infection (including three with PTLD) in association with seroconversion and a rise in EBV viral load in the peripheral blood, demonstrated by an EBV-specific polymerase chain reaction (EBV-PCR). Of 15 seroconverters, 7 who developed symptomatic infection had received EBV+ grafts; 8 others with EBV+ grafts seroconverted but did not become symptomatic. These two subgroups did not differ in age, rejection rate, antiviral prophylaxis, or level of immunosuppression. In the overall group of 81 children, only the two with malignant lymphoma who were managed with chemotherapy had substantial morbidity. The 10 individuals with PTLD received a regimen combining i.v. ganciclovir and CytoGam, and stopping or reducing the tacrolimus. Four children with associated marked tonsilar growth underwent tonsillectomy. All 19 individuals with EBV disorders resolved their symptoms and signs, and all have maintained good allograft function during a follow-up time of 3.0+/-2.5 years (mean+/-SD) after the development of symptomatic EBV infection, PTLD, or malignancy. We conclude that seronegative recipients of EBV+ grafts are at high risk for developing EBV-related disorders after renal transplantation under tacrolimus-based immunosuppression, although the ultimate clinical outcomes have been remarkably good. These data form the basis for formulating strategies for early identification of children at risk for EBV complications, and for instituting preventive and treatment strategies that permit these children to realize the substantial benefits offered by tacrolimus-based immunosuppression.

Adolescent↗
PubMed1999

The histiocytoses.

The histiocytoses, systemic disorders of the dendritic or macrophage lines, are an enigmatic group of disorders. It is hoped that by better understanding and identification of the responsible cells in each of the various conditions, their biological nature will become apparent. Because they are unusual, only multi-institutional groups, such as the Histiocyte Society, will be able to collect enough examples and bring a standardized approach to their evaluation. Those interested in joining the Histiocyte Society are invited to apply by contacting the Histiocyte Society, 302 N Broadway, Pitman, NJ 08071.

Child↗
PubMed1998

Management of posttransplant lymphoproliferative disease in pediatric liver transplant recipients receiving primary tacrolimus (FK506) therapy.

BACKGROUND: Posttransplant lymphoproliferative disease (PTLD) after pediatric liver transplantation has been associated with high mortality rates. METHODS: The present study examined 282 consecutive pediatric liver transplant recipients from October 1989 to June 1996 who received primary tacrolimus immunosuppression. The aim was to determine the incidence of PTLD, management strategies, and patient outcome. RESULTS: The incidence of PTLD was 13% (361282) with a mean age of 5.5+/-0.7 years (range 0.6 to 15) at diagnosis. The average time from transplantation to PTLD was 10.1+/-2.1 months. Initial treatment of PTLD consisted of reduction (3 patients) or discontinuation (33 patients) of tacrolimus and initiation of antiviral therapy (intravenous ganciclovir, 14 patients; intravenous acyclovir, 22 patients; or both, 5 patients). Alpha-interferon was used in four patients (two successfully). One patient also received gamma-interferon, chemotherapy, and radiation for a central nervous system lesion. Chemotherapy was also used in one patient with Burkitt's, whereas one patient with a pulmonary lesion received additional radiation therapy. Three patients received supportive surgery for gastrointestinal involvement, and one patient had a splenectomy for hemolysis. Overall mortality was 22% (8/36) with 5 (14%) PTLD-related deaths (disseminated disease, 4 patients; bowel perforation, 1 patient). Of 31 survivors, 23 had acute rejection at a median time of 24 days after PTLD, with 2 patients developing chronic rejection. One patient required retransplantation. Present immunosuppression consists of tacrolimus monotherapy in 14 patients, tacrolimus/prednisone in 8 patients, and none in 6 patients. CONCLUSION: In summary, PTLD can be successfully treated with reduction of immunosuppression and administration of antiviral agents in most patients. The management of rejection after PTLD requires reassessment of disease status and judicious reintroduction of immunosuppression therapy.

Adolescent↗
PubMed1998

Routine Coronary Arteriography Following Thrombolytic Therapy for Acute Myocardial Infarction: An Unsettled Controversy.

Although coronary artery disease remains the leading cause of death in industrialized countries, the management of patients recovering from acute myocardial infarction varies significantly. The issue of routine arteriography and revascularization following thrombolytic therapy remains controversial despite substantial evidence associating infarct-related artery patency with improved cardiac function and survival. Randomized trials of routine intervention after myocardial infarction have generally failed to demonstrate advantages of this invasive approach but methodological problems limit their application to current practice. High-risk patients should be referred for arteriography. While awaiting definitive trials addressing the influence of routine arteriography on patient survival and its cost effectiveness, the management of other patient groups must be individualized.

Journal Article↗
PubMed1998

Expression of acute otitis media after receptor blockade of platelet activating factor, thromboxane, and leukotrienes in the chinchilla.

To determine the role of inflammatory products of phospholipid metabolism in acute otitis media (AOM), we infected 128 chinchillas with Streptococcus pneumoniae and randomly assigned them to one of four equal-sized treatment groups receiving intramuscular ampicillin sodium (control) or intramuscular ampicillin plus receptor blockers of platelet activating factor (WEB 2086, 5 mg/d orally), of leukotriene (MK 571, 0.5 mg/d orally), or of thromboxaneA2 (GR 32191B, 5 mg/d orally). All treatments were begun on day 2 postinoculation and continued for 10 days. On days 3, 6, 9, and 12, 8 animals from each group were sacrificed. Effusions were recovered for biochemical assay, and the right middle ears were prepared for histologic study. Differences among groups in the number of ears with effusion or in effusion volume were not statistically significant. In comparison to the control group, mucosal thickness and the number of ears with histopathologic signs of inflammation were significantly less in the GR and WEB treatment groups, but not the MK group. Also, effusion concentrations of free fatty acids, protease, and hydrolytic enzymes were significantly less in those groups. These results show that the addition of a receptor blocker for either platelet activating factor and/or thromboxane to ampicillin in the treatment of AOM reduces mucosal inflammation and decreases the production of other inflammatory chemicals. The failure of a receptor blocker of leukotrienes to moderate disease expression suggests either a less important role for these chemicals in AOM or an insufficient bioavailability of the specific MK 571 inhibitor. These results confirm that platelet activating factor and thromboxane are active mediators of inflammation in AOM.

6-Ketoprostaglandin F1 alpha↗
PubMed1998

Continuous passive motion after repair of the rotator cuff. A prospective outcome study.

Despite the apparent success of continuous passive motion after soft-tissue procedures or joint replacements, its effect after repair of the rotator cuff is still unknown. The purpose of this prospective, randomized outcome study was to compare the results of continuous passive motion with those of manual passive range-of-motion exercises after repair of the rotator cuff. Thirty-one patients (thirty-two rotator cuffs) were randomly assigned to one of two types of postoperative management: continuous passive motion (seventeen patients) or manual passive range-of-motion exercises (fifteen patients). There were seventeen women and fourteen men, and the mean age was sixty-three years (range, thirty to eighty years). The patients were followed for a mean of twenty-two months (range, six to forty-five months). Five tears of the rotator cuff were small, eighteen were medium, and nine were large. All of the operations were performed by one surgeon. The patients who were managed with continuous passive motion used the device for the first four weeks postoperatively. The patients who were managed with manual passive range-of-motion exercises were assisted by a trained relative, friend, or home-care nurse. After the four-week period, the two groups were managed similarly for two to five months. According to the Shoulder Pain and Disability Index, a valid and reliable self-administered questionnaire, the treatment was extremely successful in both groups. The overall score was excellent for twenty-seven shoulders (84 per cent), good for two (6 per cent), fair for two (7 per cent), and poor for one (3 per cent). With the numbers available, we could detect no significant differences (p > 0.05) between the two groups with respect to the score according to the Index, pain (according to a visual-analog scale), range of motion, or isometric strength. Manual passive range-of-motion exercises were more cost-effective than continuous passive motion. The limited number of physical-therapy visits associated with the manual passive range-of-motion exercises in the present study appeared to be more cost-effective than a traditional physical-therapy schedule of three visits per week. Postoperative therapy with continuous passive motion or manual passive range-of-motion exercises appears to yield favorable results after repair of a small, medium, or large tear of the rotator cuff.

Adult↗
PubMed1998

First trimester utero-placental circulation: maternal-fetal interaction.

Progressive development of embryonal and maternal circulations is essential for normal pregnancy outcome. The early embryo and trophoblast are very sensitive to the conditions under which they grow and differentiate. The most crucial event in human ontogeny is trophoblast invasion, a process that will enable chorionic and maternal circulations to develop in a synchronized fashion, balancing the metabolic needs with the capability to defend against oxidative stress. Trophoblast invasion transforms the spiral arteries into low resistance vessels, a change necessary for establishment of continuous forward blood flow once the villi are anchored and have obtained defense mechanisms against oxidative insult. Based on a review of current knowledge of human trophoblast and embryonic growth and development of embryonic and maternal placental circulations it seems that human ontogeny occurs in a low oxygen environment during the initial stages of pregnancy. This is similar to the environment in which the first single cell organisms appeared and it remains to be seen if the development process of the primitive single cell organisms, and its energy generating processes, is an appropriate model for studying early human ontogeny.

Cell Differentiation↗
PubMed1997

Contemporary classification of histiocytic disorders. The WHO Committee On Histiocytic/Reticulum Cell Proliferations. Reclassification Working Group of the Histiocyte Society.

Pathologists and pediatric hematologist/ oncologists of the World Health Organization's Committee on Histiocytic/Reticulum Cell Proliferations and the Reclassification Working Group of the Histiocyte Society present a classification of the histiocytic disorders that primarily affect children. Nosology, based on the lineage of lesional cells and biological behavior, is related to the ontogeny of histiocytes (macrophages and dendritic cells of the immune system). Dendritic cell-related disorders of varied biological behavior are dominated by Langerhans cell histiocytosis, but separate secondary proliferations of dendritic cells must be differentiated. Juvenile xanthogranuloma represents a disorder of dermal dendrocytes, another dendritic cell of skin. The hemophagocytic syndromes are the most common of the macrophage-related disorders of varied biological behavior. Guidelines for distinguishing the exceedingly rare malignant diseases of histiocytes from large cell lymphomas through the use of a battery of special studies are provided.

Cell Lineage↗
PubMed1997

Ventricular remodeling: from bedside to molecule.

The multiple mechanisms that bring about the decompensation of the hypertrophic remodeled myocardium are synergistic and not fully understood. Our current hypothesis is that the increased stress on the ventricle is initially offset by compensatory myocardial hypertrophy. In many instances, however, progressive ventricular dilatation and heart failure occur as a result of maladaptive hypertrophy (abnormal myosin-actin production), programmed cell death (apoptosis) and/or changes in the interstitial vasculature and collagen composition. The molecular and genetic background to these processes includes changes in myocardial gene expression, activation of the local tissue renin-angiotensin and other neurohormonal systems, increased matrix metalloproteinase activity (including collagenase), and expression of certain components of the immune system, such as TNF-alpha. Future research will hopefully provide better methods for limiting the remodeling-ventricular dilatation process by novel pharmacotherapies, gene therapy and, possibly, surgical therapy, and determine the impact of such interventions on survival.

Animals↗
PubMed1997

Maternal circulation in the first-trimester human placenta--myth or reality?

The classic theory of development of the uteroplacental and intervillous circulation determined that maternal blood enters the intervillous space in high-pressure streams from the early first trimester. This theory has recently been challenged and our hypothesis to be presented is that the intervillous circulation is not fully established until the end of the first trimester. Ex vivo studies of hysterectomy specimens have demonstrated that trophoblastic plugs obstruct blood flow into the intervillous space in early pregnancy and only at 12 to 13 weeks do these plugs become loose and allow for continuous maternal blood flow into the intervillous space. This concept is supported by many other experimental findings. In complicated early pregnancies the uteroplacental circulation demonstrates flow characteristics that are strikingly different from those of normal early pregnancies. In abnormal pregnancies increased flow within the intervillous space is demonstrated by color Doppler imaging. Our hypothesis supports other studies that have shown that the embryo favors an environment low in oxygen during early development and that oxygen levels in placental tissue are low in the early first trimester. The classic drawing of placental circulations is based on second- and third-trimester studies, and its applicability to the early first trimester should be revisited because we will show that new data support the hypothesis that the development of the early intervillous circulation is a progressive phenomenon.

Chorionic Villi↗
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

Expression of SSEA-1 (Lewis(x)) on transitional cell carcinoma of the bladder.

The expression of stage-specific embryonic antigen 1 (SSEA-1) in transitional cell carcinomas of the bladder (TCCB) has been reported to correlate with tumor grade and the likelihood of lymphatic metastases. We examined the expression of this antigen in TCCBs to evaluate if staining correlated with grade, stage, recurrence, progression and response to intravesical chemotherapy. We studied the expression of SSEA-1 in TCCBs from 74 patients by staining with two different monoclonal antibodies (Mabs), P-12 and anti-SSEA-1, to evaluate if staining correlated with grade, stage and tumor recurrence. Staining was considered as positive or negative irrespective of the intensity of staining. Extent of tumor staining was measured in quartiles of 100% (25, 50, 75 and 100). Follow-up was available in 47/74 (63%) patients and ranged from 6 months to 13 years (median 2 years). Staining with one or both Mabs was observed in 57/75 (76%) tumors. None of the grade I tumors showed > 50% staining while 26% of grade II and only 33% of grade III tumors showed staining of > 50% of cells. 21% of patients whose tumors showed staining with both Mabs were free of recurrence after resection of the primary tumor; 41% of patients with tumors staining negative with both Mabs showed no recurrence. Expression of SSEA-1 does correlate with tumor recurrence especially in grade II tumors, but the correlation is not very strong (0.05 < p < 0.1). Expression of this antigen is a weak indicator of recurrence in superficial TCCBs.

Aged↗