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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

AIDS-associated non-Hodgkin's lymphomas as primary and secondary AIDS diagnoses in hemophiliacs. Hemophilia Malignancy Study Group.

We studied the characteristics and temporal trends of AIDS- associated non-Hodgkin's lymphoma (AIDS-NHL) in individuals with hemophilia. Prospective data were collected on 33 HIV-positive hemophiliacs with AIDS-NHL enrolled in the Hemophilia Malignancy Study (HMS), of whom 21 had primary and 12 had secondary or subsequent AIDS-defining illnesses, and analyzed for frequency and temporal trends. As compared with primary AIDS- NHL, secondary AIDS-NHL occurred at an older mean age, 37 versus 29 years (p = 0.12); at a lower mean CD4 count, 46 versus 154 (p = 0.07); after a longer period of immunosuppression (CD4 < 200/microl), 41 versus 16 months (p = 0.03); and with shorter median survival, 2 versus 7 months (p = 0.09). The presence of EBV in tumor tissue was associated with shorter survival, 1 versus 7 months (p = 0.17). Between 1981 and 1988 and 1989 and 1994, the proportion of primary AIDS diagnoses that were AIDS-NHL changed minimally, 4.6 versus 6.1%, whereas there were significant decreases in Pneumocystis carinii pneumonia (PCP, p = 0.02) and wasting (p = 0.07), and an increase in Candida (p = 0.004). These findings confirm that an increasing proportion of AIDS-NHL in hemophiliacs are occurring as secondary or later AIDS diagnoses, and they are associated with prolonged duration of immunosuppression.

AIDS-Related Opportunistic Infections

Tobacco promotion and susceptibility to tobacco use among adolescents aged 12 through 17 years in a nationally representative sample.

OBJECTIVES: The purpose of this study was to examine whether youth participation in tobacco promotion campaigns is associated with susceptibility to tobacco use. METHODS: Data were collected from telephone interviews of a national random sample of 1047 adolescents 12 to 17 years of age. RESULTS: A proportional odds model was used to estimate the effects of age, gender, presence of a tobacco user in the household, awareness of tobacco promotions, knowledge of a young adult or adolescent friend owning a promotional item, participation in tobacco promotions, and receipt of free tobacco samples or direct mail from tobacco companies on susceptibility to tobacco use. All of the covariates, except for receiving direct mailings and knowing a young adult friend who owned a promotional item, were significantly associated with susceptibility. CONCLUSIONS: There is a strong association between an awareness of and involvement with tobacco promotions and being susceptible to tobacco use or a user of tobacco products.

Adolescent

Multigate spectral Doppler velocimetry for fast assessment of intraplacental fetal circulation: a preliminary study.

The aim of this preliminary study was to investigate the assessment of the intraplacental fetal circulation with a new multigate Doppler system. Doppler velocimetry of the umbilical artery is widely used for assessment of fetal well-being, but its sensitivity is too low for prediction and early detection of pathologic placental processes. Intraplacental velocimetry is more accurate and detects pathologic conditions of the placenta earlier. Color Doppler imaging of intraplacental circulations is a difficult process, and the multigate system was developed to enhance the assessment of intraplacental circulation. This study shows that the multigate system is accurate and is a successful means of fast evaluation of the intraplacental circulation.

Female

The association of Epstein-Barr virus with smooth-muscle tumors occurring after organ transplantation.

BACKGROUND: Epstein-Barr virus (EBV) has been associated with nasopharyngeal carcinoma, some lymphomas, and lymphoproliferative disease after organ transplantation. Many lymphoproliferative tumors that occur after transplantation are clonal, a property that classifies them as neoplastic. Clonality can be determined by analysis of the extrachromosomal circular DNA episomes produced by EBV infection. METHODS: We describe three young children in whom smooth-muscle tumors developed 18 months to 5 1/2 years after liver transplantation with immunosuppression. We examined the tumors by microscopy and with immunohistochemical studies and molecular genetic analyses of the EBV DNA: RESULTS: The tumors were composed of spindle cells with smooth-muscle features and resembled those described in patients with the acquired immunodeficiency syndrome. Immunohistochemical analysis was negative for EBV latent membrane protein and EBV receptor (CD21), but positive for EBV nuclear antigen 2. In situ hybridization revealed nuclear EBV sequences, and molecular genetic analysis showed the EBV genome to be clonal in all three patients. CONCLUSIONS: Smooth-muscle tumors that developed after organ transplantation contained clonal EBV, suggesting that the virus has a role in the development of these neoplastic lesions.

Colonic Neoplasms

Tumor labeling in vivo using cyanine-conjugated monoclonal antibodies.

Far-red-emitting cyanine fluorochromes have many properties desirable for in vivo imaging: absorption and emission at wavelengths where blood and tissue are relatively transparent, high quantum yields, and good solubility even at high molar ratios of fluorochrome to antibody. Potentially, conjugation by multiple linkages should minimize hydrolysis in vivo. We conjugated two tumor-targeting monoclonal antibodies: anti-SSEA-1 (IgM, kappa) at ratios of 1.2-35 mol dye/mol antibody and 9.2.27 (IgG2a, kappa) at 0.6-6 mol dye/mol antibody, using the cyanine fluorochromes Cy3.18, Cy5.18, and Cy5.5.18. Nude mice were inoculated using the SSEA-1-expressing MH-15 teratocarcinoma or the 9.2.27 antigen-expressing SK-MEL-2 melanoma to give tumors at several sites. Conjugated antibody was injected, and mice were imaged immediately after injection and at appropriate intervals thereafter using a standard camera lens, dissecting microscope, or endoscopes. Images were acquired using either an image-intensified video camera or cooled CCD cameras. Immediately after injection, major blood vessels and the heart, liver, and kidneys were readily visualized. After 1 day, tumor-targeting antibody conjugates were concentrated in tumors and there was little circulating conjugate; however, the bladder and kidneys were still visible. Tumors labeled by specific antibody were the most fluorescent tissues at 2 days after injection, but non-specific antibody conjugates did not concentrate in the tumors. The small intestine was weakly visualized by both specific and non-specific antibody conjugates. These data support the possibility of visualizing tumor metastasis by optical means, including currently available endoscopes.

Animals

Adenovirus pneumonia in lung transplant recipients.

Although Adenovirus (ADV) pneumonia has been documented in bone marrow, kidney, and liver transplantation recipients, it has only been sporadically reported in lung transplantation recipients. Among our 308 lung transplantation recipients, we identified four who developed ADV pneumonia. Formalin-fixed paraffin-embedded biopsy and autopsy specimens on all cases were studied by routine histology, immunohistochemistry (IHC), and by in situ hybridization (ISH) for evidence of ADV, and the results were correlated with the patients' clinical progression. Three of the four patients were children, and all four had a progressive and rapidly fatal course within 45 days posttransplantation. The lungs showed necrotizing bronchocentric pneumonia with tendency to spread diffusely to produce alveolar damage and organizing pneumonia. The occurrence of this rapidly fatal ADV pneumonia mainly affecting the pediatric population, early in the posttransplantation course, suggests that the infection is primary to the recipient with ADV either originating and reactivating in the donor lung or acquired from the upper respiratory tract of the recipient. The characteristic smudgy intranuclear inclusions of ADV, as well as IHC and ISH positivity, were observed in the lungs of all autopsies. Antemortem biopsy demonstration of ADV by inclusion formation, IHC, and ISH was observed in two patients. In another patient, antemortem ADV was shown only by ISH, and the recognition of inclusions was made difficult by coexistent CMV infection. Although IHC and ISH may have the potential for detecting early infection, recognition of the characteristic clinical setting with necrotizing bronchocentric pneumonia and smudgy intranuclear inclusions should alert one to the diagnosis of ADV pneumonia.

Adenoviridae Infections

Treatment of experimental acute otitis media with ibuprofen and ampicillin.

The efficacy of concurrent treatment of experimental acute otitis media with ibuprofen and ampicillin was evaluated in chinchillas with respect to clearance of the effusion and resolution of mucosal inflammation. Sixty-four chinchillas were infected with Streptococcus pneumoniae and randomly assigned to treatment with either IM ampicillin (control) or ampicillin plus ibuprofen (experimental) beginning on day 2 post inoculation. On days 3, 6, 9 and 12, 8 animals from each group were killed, effusions recovered for biochemical assay and the right middle ears prepared for histological study. Between group differences in the number of ears with effusion and effusion volume were not statistically significant. Mucosal thickness and the frequencies of ears with histopathological signs of inflammation were significantly less in the experimental group when compared to the control group. Differences in the effusion concentrations of total protease, 3 of 4 hydrolytic enzymes and free fatty acids favoring the experimental group were observed at the 6, 9 and 12 day endpoints. Also, at those times the levels of the 3 measured products of the cyclooxygenase pathway were less in the experimental group. These results suggest that the addition of ibuprofen to ampicillin for the treatment of acute otitis media decreases production of select eicosonoids, reduces mucosal inflammation and alters the course of the disease in this model of bacterial infection.

Acute Disease

Pathology of intestinal transplantation in children.

The role of mucosal biopsy in the monitoring of pediatric intestinal allografts is analyzed. We performed a retrospective review of all biopsy, resection, and autopsy material from 22 bowel allografts in 21 patients, followed from 6 months to 3 1/4 years and treated on an immuno-suppressive regimen based on FK 506 (Tacrolimus). There were 579 biopsies, of which 35 were stomal, with two to three fragments taken at each biopsy. There were three explanted bowels and three autopsies. Stomal biopsies proved to be inappropriate for monitoring. Biopsies with three to five pieces of tissue per site, under endoscopic direction, provided the most information. Early cellular infiltrate with lymphoid activation in the absence of epithelial apoptotic figures was not considered sufficient to diagnose rejection although preceded it in most instances. At least two apoptotic figures in a gland or several single apoptotic cells in the presence of a lymphoid infiltrate with activated lymphoid follicles and prominent endothelium correlate best with clinical rejection and response to antirejection measures. Epstein-Barr viral disease is common in this population, and early, late, and noncontiguous bowel involvement can be subtle and difficult to distinguish from rejection, though without the apoptosis. Epstein-Barr virus in situ probes are essential to make the differential diagnosis and the two conditions may co-exist. Mucosal biopsy monitoring appears to be of clinical utility and is part of a program that involves clinical, endoscopic, microbiological, and morphologic assessment.

Adolescent

Color Doppler imaging of the uteroplacental circulation in the first trimester: value in predicting pregnancy failure or complication.

OBJECTIVE: The purpose of this study was to determine the utility of color duplex Doppler sonography of the uteroplacental circulation in predicting the outcome of first-trimester gestations. SUBJECTS AND METHODS: 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. RESULTS: 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 < .005). CONCLUSIONS: This study indicates that abnormal blood flow patterns of the early uteroplacental circulation are associated with an increased prevalence of pregnancy complications and that color Doppler imaging may be used to predict pregnancy outcome.

Abortion, Spontaneous

Failure of methotrexate treatment for term placenta percreta.

Placenta percreta is a severe condition associated with maternal morbidity and mortality even when surgery is performed electively. Methotrexate has been suggested as a possible treatment modality for adherent placenta to avoid catastrophic surgery. The purpose of this report is to present a case where the placenta was left in situ to avoid cystectomy at the time of cesarean section, with subsequent failure of treatment with methotrexate.

Adult

Overexpression of the oncoprotein p53 in primary hepatic tumors of childhood does not correlate with gene mutations.

High levels of expression of the p53 protein and gene mutations have been described in adult hepatocellular carcinomas. It has been postulated that specific mutations in exon 7 may be caused by aflatoxin exposure. To determine whether p53 mutations occur in childhood liver cancer unassociated with aflatoxin exposure or hepatitis B virus (HBV) infection, we have analyzed three histologically distinct tumor types. Two techniques were used to access p53 in the tumors: (1) expression studies of the p53 protein were performed using the polyclonal antibody CM1 and immunohistochemistry, and (2) DNA sequencing was performed. p53 Protein was detectable by immunohistochemistry in 10 of 15 hepatoblastomas, six of nine hepatocellular carcinomas, and one of one embryonal sarcomas. Solid phase single-stranded DNA sequencing across exons 5 through 9 showed normal sequence in all cases. These results indicate that p53 is overexpressed in a majority of childhood liver cancers, but this abnormal p53 expression does not seem to be caused by mutations in the p53 gene.

Base Sequence

The A1 pulley in rheumatoid flexor tenosynovectomy. To retain or divide?

We report a detailed comparative evaluation of flexor tenosynovectomy in 55 fingers in which the A1 pulley was divided and 45 fingers in which the A1 pulley was retained. The metacarpophalangeal joint subluxed volarly in 49% when the A1 pulley was divided, compared to 11% when the pulley was preserved. Bowstringing occurred in 7% and only when the A1 pulley was divided. Ulnar deviation was 7 degrees worse when the pulley was divided. Active range of movement was limited in both groups. It was 11 degrees less when the A1 pulley was divided.

Adult