P53 overexpression as an indicator of overall survival and response to treatment in osteosarcomas

The p53 gene located at chromosome 17pl3 is found to be altered (allelic loss or other mutation) in multiple human cancers, including osteosarcomas. The mutated gene produces a protein with a prolonged half-life thus rendering it detectable by conventional immunohistochemistry. We examined the correlation between p53 expression and clinical prognosis as well as response to therapy. Twentyone patients with previously untreated and histologically verified highly malignant osteosarcoma were used for this study. Biopsy material taken both prior to the start of COSS 91 protocol and at the time of surgery (ten weeks later) was examined for alterations in p53 protein expression and drug resistance. Two patients who had strong (+++) p53 protein expression and three others who became positive during the chemotherapy had significantly worse prognosis (all of them died within one year) than those who showed no p53 expression both at biopsy and after chemotherapy (all 11 patients are alive, average follow-up time: 3.5 years). All patients who showed any kind of positive p53 protein expression on initial biopsy were non-respon-ders to chemotherapy. In contrast, 69% (9 out of 13) of those who exhibited no p53 expression on initial biopsy were responders or intermediate responders to chemotherapy. We concluded that p53 expression may be a useful prognostic factor in osteosarcomas. The direct correlation between p53 positive expression and resistance to therapy can help in identifying patients who are in need of a more vigorous or different chemotherapeutical protocol.     

Physical and biomechanical issues in graft design

New vascular grafts, stents, and stent grafts require designs that use known principles of bioadhesion and biomechanics, minimizing attachment strengths of blood-borne deposits or infecting microorganisms on their lumenal walls while maximizing tissue integration with the host vasculature. Critical surface tension (CST) is an easily measured material characteristic predictive of these outcomes. CST between 20 and 30 mN/m favors easy release and thromboresistance, whereas CST between 30 and 40 mN/m promotes strong bonding.     

Efficiency of prostate-specific antigen and digital rectal examination in screening, using 4.0 ng/ml and age-specific reference range as a cutoff for abnormal values

BACKGROUND: The purpose of this study was to examine the diagnostic efficiency of prostate-specific antigen (PSA) and digital rectal examination (DRE) testing when using either 4.0 ng/ml or an age-specific reference range (ASRR) as an abnormal cutoff PSA value. METHODS: Between 1992-1995, 116,073 men, aged 40-79 years, were screened during Prostate Cancer Awareness Week. When using a 4.0-ng/ml cutoff PSA value, 22,014 had either an abnormal PSA, an abnormal DRE, or both. When using an ASRR cutoff PSA value, 17,561 had either an abnormal PSA, an abnormal DRE, or both. The positive predictive value (PPV), sensitivity, and specificity of PSA, DRE, and combined PSA and DRE tests were evaluated. RESULTS: When using a 4.0-ng/ml cutoff PSA value, the PPVs of abnormal PSA alone, abnormal DRE alone, and combined abnormal PSA and DRE tests were 27.7%, 17.7%, and 56.0%, respectively. Sensitivities were 34.9%, 27.1%, and 38.0%, respectively. Specificities were 63.1%, 49.0%, and 87.9%, respectively. When using an ASRR cutoff PSA value, the PPVs of each category were 31.8%, 20.8%, and 63.7%, respectively. Sensitivities were 27.1%, 41.0%, and 31.8%, respectively. Specificities were 75.0%, 32.8%, and 92.2%, respectively. The PPVs of the PSA test were higher than those of the DRE. The PPVs of combined tests were highest when using either a 4.0-ng/ml cutoff PSA value or an ASRR cutoff PSA value (all P < 0.001). When using an ASRR, the PPVs of PSA, DRE, and combined tests were higher than those when using a 4.0-ng/ml without statistical significance (all P > 0.05). Sensitivity of PSA when using an ASRR was lower than when using 4.0 ng/ml. CONCLUSIONS: Significantly higher PPVs indicated that utilizing both a PSA test and a DRE is most effective in screening for the early detection of prostate cancer. Although higher PPVs when using an ASRR cutoff PSA value suggested fewer unnecessary biopsies, lower sensitivities resulted in fewer cancers detected. Thus, we recommend that the combination of a PSA test with a cutoff value of 4.0 ng/ml and a DRE should continue to be utilized in the screening programs.     

Vascular and electromyographic responses evoked in forearm muscle by isometric contraction of the contralateral forearm

There is controversy over whether isometric contraction of the forearm evokes vasoconstriction or vasodilatation in the muscles of the contralateral forearm. In the present study we have investigated in normal man, the effects of isometric contraction of one arm at 75, 50 and 25% maximum voluntary contraction (MVC) on arterial pressure, heart rate, blood flow and vascular resistance of the contralateral forearm and on electromyographic (EMG) activity recorded from that same arm with sensitive, surface electrodes.When EMG activity was not being recorded from the resting arm, isometric contraction of the contralateral arm for 2 min evoked increases in arterial pressure and heart rate whose magnitudes were graded with % MVC and an increase in forearm blood flow and a decrease in forearm vascular resistance at 75, 50 and 25% MVC, indicating vasodilatation. Further experiments in which EMG activity was recorded from the resting arm demonstrated that the decrease in forearm vascular resistance evoked by 75% MVC was associated with a substantial increase in EMG activity of the extensor and flexor muscles of that arm. By contrast, when forearm contraction was performed at 75% MVC whilst subjects viewed the EMG activity in the resting arm on an oscilloscope and kept EMG activity minimal, vascular resistance increased in that arm, indicating vasoconstriction. Further, when subjects performed contraction at 25% MVC whilst showing minimal EMG activity in the contralateral arm, vascular resistance in that same arm increased (from 78 ± 16 to 124 ± 29 mmHg/ml/min/100 ml tissue). These results are discussed in relation to those of previous studies. We propose, that in normal man, isometric contraction of the forearm evokes primary vasoconstriction in the muscles of the contralateral forearm, but that this response may be overcome by muscle vasodilatation occurring secondary to unintended muscle contraction or as part of the alerting response to acute stress.     

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.     

Immunostimulatory activity of the bacterial extract OM-8

The bacterial extract OM-89 used for the prevention and treatment of recurrent urinary tract infections constitutes an effective immunostimulant in vitro and in vivo. Here we demonstrate that OM-89 shows mitogenic properties towards murine spleen cell cultures from LPS responder and non-responder mice. In macrophages the extract induces the translocation of NF-kappaB into the cell nucleus and RNI (radical nitrogen intermediates) release, which could be attributed to single fractions of the extract. Our findings on the in vitro immunostimulatory effect of OM-89, as well as its immunogenic and adjuvant properties, are of importance for understanding its therapeutic efficacy as demonstrated in clinical studies.     

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.