Antineoplastic effects of partially HLA-matched irradiated blood mononuclear cells in patients with renal cell carcinoma.

PURPOSE: Vaccines, cytokines, and other biologic-based therapies are being developed as antineoplastic agents. Many of these agents are designed to induce an autologous immune response directed against the malignancy. In contrast, hematopoietic stem-cell transplantation is being developed as a form of allogeneic immunotherapy. This study tests the tolerance and antineoplastic activity of sequential infusions of partially HLA-matched allogeneic blood mononuclear cells (obtained from relatives) when administered outside of the context of a hematopoietic stem-cell transplantation. The cells are irradiated to prevent graft-versus-host disease. PATIENTS AND METHODS: Fifteen patients with relapsed or refractory malignancies for which no standard therapy was available were enrolled onto a clinical trial designed to assess the tolerability and antineoplastic effects of irradiated partially HLA-matched blood mononuclear cells obtained from relatives. RESULTS: There was disease regression in three patients with metastatic renal cell carcinoma during treatment. There was disease progression in six patients with metastatic renal cell carcinoma and two patients with metastatic melanoma during treatment. There was no change in disease state in several other patients. CONCLUSION: Irradiated allogeneic blood mononuclear cells administered outside the context of hematopoietic stem-cell transplantation may induce disease responses in patients with relapsed or refractory malignancies. Transfusion of irradiated allogeneic blood mononuclear cells should be developed further as a novel therapeutic antineoplastic approach.     

Foetal cystic abdominal masses

Foetal abdominal cysts are frequently found on routine antenatal ultrasound. Various sonographic features might help in their differential diagnosis. However, a definitive diagnosis is often not made until postnatal life, and detection of an intra‐abdominal cyst antenatally rarely alters obstetric management. A review of possible causes of a foetal abdominal cyst is presented.     

A randomized controlled trial of a new fetal acoustic stimulation test for fetal well-being

OBJECTIVES: Our purpose was to determine (1) whether a fetal acoustic stimulation test results in more palpable fetal movement compared with a mock test (control) and (2) whether palpated fetal movements after a fetal acoustic stimulation test are accompanied by a reactive nonstress test.STUDY DESIGN: In a randomized controlled trial we studied women seen in the labor and delivery suite for various indications. Women were excluded for multiple gestation, <31 weeks' gestational age, treatment with magnesium sulfate or narcotics, or ruptured membranes. Informed consent was obtained from eligible women, who were then randomized to a test or control group. We placed an acoustic stimulator on the abdomen of each woman, but only the test group was stimulated. We assessed fetal movement by a grading system: 0 = no fetal movement felt by patient or tester, 1 = fetal movement felt by patient only, 2 = fetal movement felt by tester, 3 = visual movement seen by tester. A positive fetal acoustic stimulation test result was defined as one with any fetal movement felt or seen by the tester (grades 2 or 3). We then performed a nonstress test. We compared rates of a positive fetal acoustic stimulation test in the test and control groups with the χ² test. A p value <0.05 was considered significant.RESULTS: We randomized 297 women to the test group and 280 women to the control (mock test) group. Of women tested with the fetal acoustic stimulation test, 81% had fetal movement by palpation or visualization (grades 2 or 3) compared with 19% of the control group (p < 0.0001, odds ratio 19.29, 95% confidence interval 12.42 to 30.07). Of the test group, 283 (95%) had a reactive nonstress test and 14 (5%) had nonreactive tests; the control group had 267 (95%) reactive and 13 (5%) nonreactive nonstress tests. Of 242 patients in the test group with a positive fetal acoustic stimulation test, 236 (98%) had a reactive nonstress test. Of those in the test group with fewer than three contractions per 10 minutes, 164 (89%) had a positive fetal acoustic stimulation test. Of these, 162 (99%) had a reactive nonstress test.CONCLUSION: The fetal acoustic stimulation test evokes significantly more palpated or visualized fetal movement than in controls. Palpated or visualized fetal movement after acoustic stimulation was almost always accompanied by a reactive nonstress test. (Am J Obstet Gynecol 1997;176:1386-8.)     

Primary ilio-psoas abscess extending to the thigh in a neonate: US, CT and MR findings

Psoas abscess in children, and especially in neonates, is an uncommon condition which is difficult to diagnose clinically. The US, CT and MR findings of a psoas abscess in a neonate, which extended to the thigh, are reported. Imaging was helpful in revealing the abnormality, in demonstrating its extension and in determining its nature. The child was treated conservatively and the abscess resolved, leaving atrophy of the psoas muscle. Received: 24 June 1997 Accepted: 9 January 1998     

Molekulare Aspekte und diagnostische Wertigkeiten von Pilzallergenen

Zusammenfassung. Die Klonierung, Sequenzierung und Produktion von hochreinen Allergenen bietet die Möglichkeit, perfekt standardisierte Allergenpräparate herzustellen. Die Entwicklung eines neuen Klonierungssystems, das auf filamentösen Phagen basiert, führte zu einer schnellen Isolierung und Charakterisierung von Aspergillus fumigatus-Allergenen. Die auf diesem Weg rekombinant hergestellten Proteine wurden serologisch und klinisch geprüft und ihr routinemä-ßiger Einsatz im ImmunoCAP-System evaluiert. Es gelang eine quantitative Übereinstimmung zwischen Hauttestergebnissen und Serologie nachzuweisen, welche das Potential rekombinanter Allergene in der Diagnostik allergischer Krankheiten aufzeigt. Darüber hinaus trägt die Charakterisierung der Pilzallergene wesentlich zum Verständnis der moiekularen Natur der allergieauslösenden Komponenten bei Zum jetzigen Zeitpunkt können, abgesehen von Proteinen mit unbekannten biologischen Funktionen, die Pilzallergene in zwei Klassen eingeteilt werden: 1. Spezies-spezifische sezcrnierte Allergene und 2. cytoplasmatische, hoch konservierte Proteine. Diese letztgenannten Pilzallergene zeigen auch zu Proteinen aus phylogenetisch weit entfernten Organismen weitreichende Sequenzhomologien. Neben der daraus zu erwartenden IgE-Kreuzreaktivität findet man in einigen Fällen auch eine Kreuzreaktivität mit den homologen humanen Proteinen, was auf Autoimmunreaktionen, bei Pilzalleigien hindeutet. Summary. Cloning, sequencing and production of highly pure recombinant allergens allows to produce perfectly standardised allergen preparations. The development of a new cloning system based on filamentous phage allowed the fast isolation and characterisation of allergens from the fungus Aspergillus fumigatus. The produced recombinant allergens were tested in serological and clinical studies as well as for their performance for routine assessments in the ImmunoCAP-system. Thereby, a perfect correlation between skin test results and serology was found showing the potential of recombinant allergens for the diagnosis of allergic diseases. Moreover, the characterisation of fungal allergens substantially contributes to our understanding of the molecular nature of proteins involved in the elication of allergic reactions. Apart from allergenic proteins with unknown biological function, fungal allergens can be subdivided into two classes: 1. Species-specific, secreted proteins and 2. cytoplasmic, even in phylogenetically distant organisms, well conserved proteins. These fungal allergens show extended sequence similarity, a high level of IgE cross-reactivity and in some cases also cross-reactivity with homologous human proteins indicating autoimmune reactions involved in fungal allergy.     

MR imaging of the neonatal brain at 3 Tesla

3 Telsa MR scanners are now becoming more widely available and 3 Telsa is likely to become the filed strength of choice for clinical imaging of the brain. The neonatal brain can be safely and successfully imaged at 3 Telsa. The improved signal to noise afforded by a higher field strength may be used to improve image quality or shorten acquisition times. This may be exploited for conventional T1 and T2 weighted imaging and also for advanced techniques such as diffusion tensor imaging, angiography and functional magnetic resonance studies.     

Do placental sections accurately reflect umbilical cord nucleated red blood cell and white blood cell differential counts?

OBJECTIVE: Elevated levels of umbilical cord nucleated red blood cells (nRBCs) have been used to assess in utero hypoxia. Although the umbilical nRBC value has been the 'gold standard', umbilical blood may not be obtained at delivery. We determined if the levels of nRBCs and white blood cell (WBC) counts in fixed placental sections might serve as a proxy for cord blood values. STUDY DESIGN: Umbilical blood and placenta were collected from 25 deliveries at Harbor-UCLA Medical Center. Umbilical blood and placental sections were analyzed for nRBCs (per 100 WBC) and WBC differential, and compared with the t-test or the Mann-Whitney rank sum test. RESULTS: nRBC counts were equivalent in umbilical cord and placental sections (5 vs. 4/100 WBC). Umbilical lymphocyte and polymorphonuclear leukocyte (PMN) counts were normally distributed, averaging 35 +/- 9 and 56 +/- 2/100 WBC, respectively. Placental lymphocyte (33 +/- 2/100 WBC) and PMN (60 +/- 2/100 WBC) counts were equivalent to cord blood values. CONCLUSION: WBC differentials and nRBC counts are equivalent in umbilical cord blood and processed placental pathology sections. For infants in whom cord blood cell counts are desired though umbilical cord samples are unavailable, fixed placental sections may serve as a proxy.     

Predictive factors of local-regional recurrences following parotid sparing intensity modulated or 3D conformal radiotherapy for head and neck cancer.

BACKGROUND AND PURPOSE: Predictive factors for local-regional (LR) failures after parotid-sparing, Intensity modulated (IMRT) or 3D conformal radiotherapy for head and neck (HN) cancers were assessed. PATIENTS AND METHODS: One hundred and fifty-eight patients with mostly stages III-IV HN squamous cell carcinoma underwent curative bilateral neck irradiation aimed at sparing the parotid glands. Patient, tumor, and treatment factors were analyzed as predictive factors for LR failure. RESULTS: Twenty-three patients had LR recurrence (19 in-field and four marginal). No differences were found in the doses delivered to the PTVs of patients with or without in-field recurrences. In univariate analysis, tumor site was highly predictive for LR failure in both postoperative and definitive RT patients. In postoperative RT patients, pathologic tumor size, margin status, extracapsular extension (ECE) and number of lymph node metastases, were also significantly predictive. Multivariate analysis showed tumor site (oropharynx vs. other sites) to be a significant predictor in all patients, and involved margins and number of involved lymph nodes in postoperative patients. CONCLUSIONS: Clinical rather than dosimetric factors predicted for LR failures in this series, and were similar to those reported following standard RT. These factors may aid in the selection of patients for studies of treatment intensification using IMRT.     

Epstein-Barr virus as a marker of survival after Hodgkin's lymphoma: a population-based study.

PURPOSE: Epstein-Barr virus (EBV) in Hodgkin's lymphoma (HL) cells has been considered as a prognostic marker for this heterogeneous disease, but studies have yielded mixed findings, likely because of selected patient series and failure to acknowledge an effect of age on outcome. This study assessed survival after HL in a population-based cohort large enough to examine the joint effects of EBV with other factors including age, sex, and histologic subtype. PATIENTS AND METHODS: Included were 922 patients with classical HL diagnosed between mid-1988 and 1997 in the Greater San Francisco Bay Area, with archived biopsy specimens assayed for EBV with immunohistochemistry and in situ hybridization. Vital status was followed through December 30, 2003 (median follow-up time, 97 months). Overall and disease-specific survival were analyzed with the Kaplan-Meier method and Cox proportional hazards regression models. RESULTS: In children less than 15 years old, EBV presence was suggestively associated (P = .07) with favorable survival. In adults aged 15 to 44 years, EBV did not affect HL outcome, although a protective effect was suggested. In older adults (45 to 96 years), EBV presence nearly doubled the risk of overall and HL-specific mortality but only for patients with nodular sclerosis (NS) histologic subtype (hazard ratio for death = 2.5; 95% CI, 1.5 to 4.3). CONCLUSION: In HL, EBV tumor cell presence is associated with better survival in young patients and poorer survival in older patients with NS, independent of other factors. Variation in outcome by age and histology could indicate biologically distinct disease entities. Evidence that EBV is a meaningful prognostic marker may have therapeutic relevance.