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Biomedical subjects

R Jaffe

Publications and source records attributed to R Jaffe.

At least 19 recordsLinked to original sources
PubMed2004

Hodgkin-like posttransplant lymphoproliferative disorder in children: does it differ from posttransplant Hodgkin lymphoma?

Epstein-Barr virus (EBV)-mediated lymphoid proliferations occur in patients who are immunocompromised and are reported following bone marrow or solid organ transplantation. Most post-transplant lymphoproliferative disorders (PTLD) are polymorphic in appearance; some are monomorphic and can resemble conventional malignant lymphomas. PTLD that resembles Hodgkin lymphoma has been reported infrequently. We herein report seven cases of PTLD that have large numbers of Reed-Sternberg-like (RS-like) cells and highlight differences in the phenotype of these cases that may distinguish Hodgkin-like PTLD (HL-PTLD) from true Hodgkin lymphoma/disease (HD). All patients were in the second decade of life and were 8 months to 13 years following transplant. HL-PTLD involves lymph nodes that contain a mixed population of small to intermediate-sized lymphocytes with large mononuclear and occasionally binucleate RS-like cells. The large cells of HL-PTLD are pleomorphic B cells that react strongly for CD20 and/or CD79a, express CD30, but are usually negative for CD15 and have few mitoses. They are positive for EBV early RNA (EBER) using an EBER-1 probe, as are some of the background small lymphocytes. A single case of true Hodgkin lymphoma has highly atypical RS-like cells that contain numerous mitoses, does not have CD20 or CD79a reactivity, has CD15 and CD30 staining, and the EBER-1 probe is confined to the large cells only. All patients were managed by withdrawal of immunosuppression and variably treated with either antiviral or anti-CD20 monoclonal antibody, or with chemotherapy. A unique instance of evolution from a HL-PTLD to true HD is also illustrated. In conclusion, HL-PTLD and HD appear to be two related but immunophenotypically and biologically distinct forms of lymphoproliferation in post-transplant patients and may require different protocols for their management.

Adolescent↗
PubMed2002

Primary cerebral non-Langerhans cell histiocytosis: MRI and differential diagnosis.

We report a young woman with primary cerebral non-Langerhans cell histiocytosis of the juvenile xanthogranuloma family. The clinical course was complicated by extensive infiltration of cranial nerves and meninges and epi- and intramedullary spinal dissemination. Whereas the cutaneous form of juvenile xanthogranuloma is usually benign and self-limited, central nervous system involvement is associated with high morbidity and mortality and might therefore be considered a separate clinical entity.

Adult↗
PubMed2001

Interaction between Hg(II) and natural dissolved organic matter: a fluorescence spectroscopy based study.

Interaction between Hg(II) and dissolved organic matter (DOM) collected from surface water samples of the Florida Everglades was studied using different fluorescence spectroscopic methods. Complexation between Hg(II) and DOM leached from mangrove leaves, sawgrass, and periphyton was investigated. Both fluorescence emission and synchronous fluorescence spectra showed that these dissolved organic materials, whether they are highly degraded or are freshly leached, can "complex" Hg(II) since fluorescence intensity was quenched upon addition of Hg(II) to the DOM samples. Synchronous fluorescence spectra disclosed structural information on the DOM sample, regarding possible binding sites for Hg(II). Chemical parameters on the complexation of Hg(II), including the conditional stability constants and the percentage of fluorophores participating in the complexation, were estimated by the modified Stern-Volmer equation. A detailed investigation under different experimental conditions showed that the complexation of the DOM samples collected from the Everglades was influenced by pH, Cl-(aq) anion, and cations such as Ca2+ and Mg2+. Experimental results suggest that DOM-Hg(II) complexes can be removed from the water column through adsorption on biogenically precipitated CaCO3(s).

Florida↗
PubMed2001

The role of genetic abnormalities of PTEN and the phosphatidylinositol 3-kinase pathway in breast and ovarian tumorigenesis, prognosis, and therapy.

Breast and ovarian cancers exhibit similar epidemiologic, genotypic, and phenotypic characteristics. Phosphatidylinositol 3-kinase (PI3K) and the PTEN tumor suppressor gene product phosphorylate and dephosphorylate the same 3' site in the inositol ring of membrane phosphatidylinositols. Germ-line mutations in the PTEN tumor suppressor gene are causative of Cowden's breast cancer predisposition syndrome, and PTEN is frequently mutated in sporadic breast cancers. In contrast, amplification of multiple components of the PI3K pathway is a hallmark of serous epithelial ovarian cancers. The resultant activation of the PI3K pathway in both breast and ovarian cancers contributes to cell-cycle progression, decreased apoptosis, and increased metastatic capabilities. Strikingly, both ovarian and breast cancer cells are selectively sensitive to pharmacologic and genetic manipulation of the PI3K pathway, making molecular therapeutics targeting this pathway particularly attractive approaches for these cancers.

Animals↗
PubMed2001

Primary tacrolimus (FK506) therapy and the long-term risk of post-transplant lymphoproliferative disease in pediatric liver transplant recipients.

While the overall incidence of post-transplant lymphoproliferative disease (PTLD) in pediatric liver transplant recipients has been reported to be 4-11%, the long-term risk of PTLD associated with primary tacrolimus therapy is unknown. Therefore, in order to determine the incidence and long-term risk of PTLD, the present study examined 131 pediatric recipients who underwent liver transplantation (LTx) between October 1989 and December 1991 and received primary tacrolimus therapy. This cohort of children was evaluated over an extended time-period (until December 31 1996) with a mean follow-up of 6.3 yr. Actuarial Kaplan-Meier analysis was utilized to determine the risk of PTLD over time. The overall incidence of PTLD was 13% (17/131) with an average age of 4.3 +/- 0.75 yr at diagnosis. Pretransplant Epstein-Barr virus (EBV) serologies were negative in 82%, positive in 12%, and not available in 6% of the patients. The median time to diagnosis of PTLD post-Tx was 11.9 months (mean 16.4 +/- 3.9, range 1.7-63.0 months). Mean tacrolimus dose and plasma trough level (as evaluated by enzyme-linked immunosorbent assay [ELISA]) at the time of diagnosis was 0.32 +/- 0.06 mg/kg/day and 1.3 +/- 0.3 ng/mL, respectively. The cumulative long-term risk of PTLD was found to increase over time: 3% at 6 months, 8% at 1 yr, 12% at 2 yr, 14% at 3 yr, and 15% at 4 and 5 yr. Mortality from PTLD was 12% (two of 17 patients). Primary tacrolimus use in pediatric LTx has a long-term risk of PTLD approaching 15%, with the majority of episodes (78%) occurring in the first 2 yr, suggesting that intense EBV surveillance should occur early post-transplantation.

Adolescent↗
PubMed2001

Three-dimensional ultrasonography in early pregnancy.

Three-dimensional ultrasound was introduced into clinical use over a decade ago. Early attempts on three-dimensional ultrasound were primitive and limited to experimental use only. Recently, it was used as a powerful tool to display three-dimensional fetal appearance and assess normal and pathological conditions. Because of the improvement in image resolution and reconstruction speed, three-dimensional ultrasound is now more and more popular in many centers, and used commonly as an adjunct in prenatal diagnosis. Indeed, a skillful sonographer may usually make the correct diagnosis of fetal anomaly with simply two-dimensional ultrasound. Nonetheless, the situation is gradually changing, because some anomalies have been diagnosed only based on the findings of three-dimensional ultrasound. In spite of that, the application of three-dimensional ultrasound is still less discussed in early pregnancy. In this article, the authors clarify the capability of three-dimensional ultrasound in different anatomic areas, and catalog its clinical merits in the early pregnancy to date. We also present the safety guidelines for its use in the first trimester.

Embryonic and Fetal Development↗
PubMed2001

Development of early uteroplacental circulation.

A crucial event in human development is trophoblast invasion, a process that will enable chorionic and maternal circulations to develop in a synchronized fashion. Early embryo and trophoblast are very sensitive to the conditions in which they grow, and progressive development of placental circulations is essential for normal pregnancy development. It has been demonstrated that inadequate trophoblast invasion is a major finding in many clinical deleterious conditions facing the obstetrician. Pathologic studies of placentas of pregnancies complicated by intrauterine growth restriction or preeclampsia demonstrate shallow trophoblast invasion of the spiral arteries. This has also been seen in early spontaneous miscarriages. In our study, we used color Doppler sonography to assess the uteroplacental circulation and predict outcome of first-trimester gestations. One hundred women with viable pregnancies of 7 to 12 weeks gestational age were prospectively evaluated. Color Doppler imaging was used to identify the location of blood flow within the uteroplacental circulation, and spectral Doppler imaging was used to analyze waveforms obtained from the decidual spiral arteries. Abnormal color Doppler findings were associated with a significantly higher prevalence of complicated pregnancies. Among women with abnormal Doppler findings, 12 (43%) of 28 pregnancies ended in miscarriage, whereas among women with normal findings only one (1.4%) of 72 women miscarried (p<.055). This study indicates that abnormal flow patterns of the early uteroplacental circulation due most likely to abnormal trophoblast invasion are associated with an increased prevalence of pregnancy complications. What causes inadequate invasion remains a mystery. Abnormal nitric oxide synthesis, due to possible endothelial cell dysfunction, has been demonstrated in some of these complicated pregnancies but, whether this is cause of effect, is not known. Every step of embryonal-maternal interaction from fertilization and onward has major implications on subsequent development of embryo, fetus, neonate and adult human being. Trophoblast invasions and transformation of the spiral arteries are possibly the most significant interactions and will have the most profound effect on pregnancy development.

Abortion, Spontaneous↗
PubMed2000

Atopic dermatitis.

Atopic dermatitis is a chronic skin disorder. It affects up to 15% of the childhood population in the United States and more than half of these patients into adulthood. A clinical diagnosis is made based on the superficial, inflammatory, erythematous and puritic eruptions. Control of symptoms involves patient and parent education with regard to skin care and avoidance of triggers. Treatment includes corticosteroids, with newer strategies emerging.

Dermatitis, Atopic↗
PubMed2000

Cryptosporidial infections after solid organ transplantation in children.

The diagnosis and treatment of moderate-to-severe diarrhea in solid organ transplant recipients is often a challenge because of the variety of infectious and non-infectious causes. The morbidity associated with this clinical condition is of particular significance in the pediatric population where malnutrition may lead to poor growth and development. Rarely, Cryptosporidium has been identified as the cause of clinically significant diarrhea in pediatric solid organ transplant patients. A retrospective review identified cases of cryptosporidiosis among the 1160 non-renal, abdominal organ transplant recipients cared for at the Children's Hospital of Pittsburgh between 1981 and June 1998. Four cases of clinically significant diarrhea were identified in three liver transplant recipients and one small bowel transplant recipient. Endoscopy and biopsy with histologic confirmation diagnosed three cases; ova and parasitic examination of stool specimens identified the fourth case. Therapy varied among the patients depending on when they had been diagnosed as, over the years, different and newer agents have been indicated for the treatment of cryptosporidiosis. All four patients resolved their infections. Hence, endoscopy and biopsy is recommended for pediatric transplant patients who present with chronic diarrhea of unknown etiology. The patients who may be at a higher risk for cryptosporidial infections include those with an increased immunosuppressive state (i.e. pre-existing immunodeficiency, malignancy, re-transplantation, and those receiving higher doses of immunosuppressive therapy). While cryptosporidiosis is a non-lethal complication, it allows the clinician to gain further insight into the degree of immunosuppression of their patient.

Adolescent↗
PubMed2000

Ocular nonnephropathic cystinosis: clinical, biochemical, and molecular correlations.

Ocular nonnephropathic cystinosis, a variant of the classic nephropathic type of cystinosis, is an autosomal recessive lysosomal storage disorder characterized by photophobia due to corneal cystine crystals but absence of renal disease. We determined the molecular basis for ocular cystinosis in four individuals. All had mutations in the cystinosis gene CTNS, indicating that ocular cystinosis is allelic with classic nephropathic cystinosis. The ocular cystinosis patients each had one severe mutation and one mild mutation, the latter consisting of either a 928 G-->A (G197R) mutation or an IVS10-3 C-->G splicing mutation resulting in the insertion of 182 bp of IVS10 into the CTNS mRNA. The mild mutations appear to allow for residual CTNS mRNA production, significant amounts of lysosomal cystine transport, and lower levels of cellular cystine compared with those in nephropathic cystinosis. The lack of kidney involvement in ocular cystinosis may be explained by two different mechanisms. On the one hand (e.g. the G197R mutation), significant residual cystinosin activity may be present in every tissue. On the other hand (e.g. the IVS 10-3 C-->G mutation), substantial cystinosin activity may exist in the kidney because of that tissue's specific expression of factors that promote splicing of a normal CTNS transcript. Each of these mechanisms could result in minimally reduced lysosomal cystine transport in the kidneys.

Amino Acid Transport Systems, Neutral↗
PubMed2000

Liver transplantation and chemotherapy for hepatoblastoma and hepatocellular cancer in childhood and adolescence.

OBJECTIVE: To describe our experience with total hepatectomy and liver transplantation as treatment for primary hepatoblastoma (HBL) and hepatocellular carcinoma (HCC) in children. STUDY DESIGN: A retrospective analysis of the perioperative course of 31 children with unresectable primary HBL (n = 12) and HCC (n = 19) who underwent transplantation between May 1989 and December 1998. Systemic (n = 18) and intraarterial (n = 7) neoadjuvant chemotherapy were administered; follow-up ranged from 1 to 185 months. RESULTS: For HBL, 1-year, 3-year, and 5-year posttransplantation survival rates were 92%, 92%, and 83%, respectively. Intravenous invasion, positive hilar lymph nodes, and contiguous spread did not have a significant adverse effect on outcome; distant metastasis was responsible for 2 deaths. Intraarterial chemotherapy was effective in all patients treated. For HCC, the overall 1-year, 3-year, and 5-year disease-free survival rates were 79%, 68%, and 63%, respectively. Vascular invasion, distant metastases, lymph node involvement, tumor size, and gender were significant risk factors for recurrence. Intraarterial chemotherapy was effective in 1 of 3 patients. Six patients died of recurrent HCC, and 3 deaths were unrelated to recurrent tumor. CONCLUSION: Liver transplantation for unresectable HBL and HCC can be curative. Risk factors for recurrence were significant only for HCC, with more advanced stages amenable to cure in the HBL group.

Adolescent↗