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At least 19 recordsLinked to original sources
PubMed2001

The origins of informed consent: the International Scientific Commission on Medical War Crimes, and the Nuremburg code.

The Nuremberg Code has generally been seen as arising from the Nuremberg Medical Trial. This paper examines developments prior to the Trial, involving the physiologist Andrew Conway Ivy and an inter-Allied Scientific Commission on Medical War Crimes. The paper traces the formulation of the concept of a medical war crime by the physiologist John West Thompson, as part of the background to Ivy's code on human experiments of 1 August 1946. It evaluates subsequent responses by the American Medical Association, and by other war crimes experts, notably Leo Alexander, who developed Ivy's conceptual framework. Ivy's interaction with the judges at Nuremberg alerted them to the importance of formulating ethical guidelines for clinical research.

Ethics, Medical↗
PubMed2003

Ethics in human experimentation: the two military physicians who helped develop the Nuremberg Code.

The Nuremberg Code is generally considered the beginning of modern ethics in human experimentation. The Code is a list of 10 principles that Judge Walter Beals included in the judgment he delivered at the close of the Nuremberg Medical Trial on 19 August 1947. Recently, scholars have studied the origin of the Code, who wrote it, and why. This is important to military medicine and the Aerospace Medical Association in particular because many of the defendants claimed their crimes were experiments in aviation and environmental physiology conducted under wartime conditions. The chief prosecutor of the Nuremberg Medical Trial, General Telford Taylor, relied on the guidance of an advisor provided by the American Medical Association, Andrew C. Ivy, one of the foremost physiologists of his time. The neurologist, Leo Alexander, then a colonel in the U.S. Army Reserves, was another medical advisor. Both men were crucial to the development of Taylor's courtroom strategy. The material Alexander and Ivy provided was incorporated verbatim in the section of the judgment that became the Code. Although both men contributed to the Code, Ivy provided what seems to be the first formulation of many of these principles during a meeting of Allied medical investigators at the Pasteur Institute in July 1946. Naval researchers should note that Ivy had been the Director of the Research Division of the Naval Medical Research Institute when it was commissioned on October 27, 1942.

Aerospace Medicine↗
PubMed2006

Near-field scanning optical microscopy in cell biology and cytogenetics.

Light microscopy has proven to be one of the most versatile analytical tools in cell biology and cytogenetics. The growing spectrum of scientific knowledge demands a continuous improvement of the optical resolution of the instruments. In far-field light microscopy, the attainable resolution is dictated by the limit of diffraction, which, in practice, is about 250 nm for high-numerical-aperture objective lenses. Near-field scanning optical microscopy (NSOM) was the first technique that has overcome this limit up to about one order of magnitude. Typically, the resolution range below 100 nm is accessed for biological applications. Using appropriately designed scanning probes allows for obtaining an extremely small near-field light excitation volume (some tens of nanometers in diameter). Because of the reduction of background illumination, high contrast imaging becomes feasible for light transmission and fluorescence microscopy. The height of the scanning probe is controlled by atomic force interactions between the specimen surface and the probe tip. The control signal can be used for the production of a topographic (nonoptical) image that can be acquired simultaneously. In this chapter, the principle of NSOM is described with respect to biological applications. A brief overview of some requirements in biology and applications described in the literature are given. Practical advice is focused on instruments with aperture-type illumination probes. Preparation protocols focussing on NSOM of cell surfaces and chromosomes are presented.

Animals↗
PubMed2005

Macrophage migration inhibitory factor: a central regulator of wound healing.

Age-associated differences in estrogen levels critically modify the cutaneous wound healing response. Using a microarray-based approach, we profiled changes in gene expression within the wounds of mice that were wild type or null for the pro-inflammatory cytokine macrophage migration inhibitory factor (MIF) in the presence or absence of estrogen. This experimental design identified more than 600 differentially expressed genes and established MIF as a key player in the wound healing process, regulating many novel repair/inflammation-associated gene targets. Moreover, MIF affected virtually all of the effects of reduced estrogen on wound repair. In humans, serum and wound levels of MIF increased with age and were strongly down-regulated by estrogen in vivo. Estrogen-regulated MIF transcription in vitro via a nuclear factor kappaB-dependent mechanism. These findings have wide-ranging implications for the many pathophysiological states in which MIF plays an important regulatory role and suggest a potential therapeutic role for MIF in modulating clinical conditions associated with age-related decline in estrogen levels.

Adult↗
PubMed2003

Psychometric- and quality-of-life assessment in long-term glioblastoma survivors.

BACKGROUND: Multimodal treatment of patients with glioblastoma multiforme (GBM) allows an increasing number of patients to survive beyond one year. On account of various neurological and psychophysiological impairments, however, these patients may not benefit in terms of quality of life (QOL). We evaluated the subjective QOL, clinical psychophysiological and cognitive functions in patients with GBM surviving 18 months after diagnosis. PATIENTS AND METHODS: Thirteen patients underwent psychophysiological and psychometric measurements for central-nervous activation, habituation of skin-conductance reaction, crystallized intelligence, verbal and psychovisual memory. QOL was assessed by the symptom check-list for somatization (SCS-Score). RESULTS: We found various impairments such as central-nervous deactivation (n = 9) or high activation (n = 3), psychovegetative overexcitement (n = 3) or attenuation (n = 1), reduced verbal (n = 5) and/or psychovisual (n = 5) memory and loss in attention (n = 7) or concentration (n = 5). Severe physical symptoms (grade 5) were fatigue, convulsion, headache, nausea and micturition difficulties. Eleven patients expressed high satisfaction with life in general, whereas only 4 were satisfied with their general state of health. All patients were independent and 8 patients returned to work. CONCLUSION: Despite various psychophysiological and cognitive impairments, subjective QOL appears mostly unaffected in this patient setting.

Adolescent↗
PubMed2002

Is duplex ultrasonography an effective single modality for the preoperative evaluation of peripheral vascular disease?

The purpose of this study was to determine whether duplex ultrasonography can be used as an effective modality for the preoperative evaluation of lower-extremity arterial occlusive disease. The records of all patients undergoing both color flow duplex scanning and contrast arteriography of the lower extremities during a 13-month period were reviewed. Comparisons between the two modalities were made at the femoral, popliteal, and tibial artery levels. Sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy were calculated for duplex scanning using angiography as the gold standard. Three hundred fifteen arterial segments were evaluated. Color flow imaging overestimated the degree of stenosis in seven vessels and underestimated the degree of stenosis in four vessels. Overall duplex ultrasonography accurately determined lower-extremity arterial anatomy as defined by contrast arteriography with a sensitivity of 96.9 per cent, a specificity of 96.2 per cent, a positive predictive value of 94.6 per cent, a negative predictive value of 97.8 per cent, and an overall accuracy of 96 per cent. The accuracy of duplex ultrasonography must be determined in each individual vascular laboratory. Once this is satisfactorily accomplished color flow scanning may be used as the single imaging modality for lower-extremity arterial occlusive disease in selected patients deemed to be at high risk for contrast angiography.

Aged↗
PubMedDate not supplied

[Methicillin-resistant Staphylococcus aureus (MRSA) in veterinary medicine: a "new emerging pathogen"?].

The problem of nosocomial infections is of increasing importance in veterinary medicine. As an example, this review summarizes current knowledge regarding methicillin-resistant Staphylococcus aureus (MRSA) as a typical example, as these pathogens are the most important agents of nosocomial infections in human medicine worldwide and are being increasingly reported in veterinary medicine. MRSA are classified by their ability to be resistant against oxacillin/methicillin, this feature being confered by mecA, a gene which was acquired by horizontal gene transfer of the staphylococcal gene cassette (SCCmec). It is this genetic information that enables MRSA to be resistant against all penicillins, cehalosporins and carbapenems. In addition, MRSA are often resistant against a variety of other antiinfectives, i.e. aminoglycosides, macrolides, lincosamide, streptomycins, tetracyclin, chloramphenicol, but also against fluorquinolones and rifampicin. Presumably, these highly adapted strains are particularly able to acquire resistance genes located on plasmids or transposons. They are also able to develop point mutations, further leading to resistant phenotypes. If these pathogens are leading to infectious diseases, veterinarians may be confronted with a worst-case scenario, being left without any antiinfective therapeutic. As Staphylococcus aureus is highly tenacid, professional hygiene management is of utmost importance. The increasing number of published sporadic MRSA infections, MRSA-infectious diseases as well as MRSA outbreaks in veterinary medicine justifies their recognition as a "New Emerging Pathogen". So far, horses and dogs are mostly affected by MRSA. Although transmission between humans and animals has been reported occasionally, the sources, routes of transmission or the epidemiological relevance of MRSA infections in animals are far from being understood. Therefore, epidemiological investigations utilizing molecular typing tools are mandatory. Typing tools like multilocus-sequence-typing (MLST), pulsefield-gelelectrophoresis (PFGE), sequence analysis of the gene encoding protein A (spa-typing) as well as SCCmec-typing are all at hand.

Animals↗
PubMed2004

Expression pattern of FCRL (FREB, FcRX) in normal and neoplastic human B cells.

FCRL (also known as FREB and FcRX) is a recently described member of the family of Fc receptors for immunoglobulin G (IgG). In the present study we analysed its expression in normal and neoplastic lymphoid tissue using immunohistochemical techniques. FCRL was preferentially expressed in a proportion of germinal centre cells and, more weakly, in mantle zone B cells. In addition, strong labelling was observed in marginal zone B cells in the spleen, representing one of the few markers for this cell type. The majority of cases of small B-cell lymphoma, diffuse large B-cell lymphoma and lymphocyte predominance Hodgkin's disease were positive for FCRL. However, the number of positive cells varied widely, and in consequence we could not define a cut-off that distinguished subsets of diffuse large B-cell lymphoma. Our results also showed that FCRL tended to be negative in T-cell-rich B-cell lymphoma and in classical Hodgkin's disease. FCRL may therefore represent a novel marker for normal B cells (e.g. splenic marginal zone cells) and may also be useful as a potential marker of B-cell neoplasms.

B-Lymphocytes↗
PubMed2006

Juxtatumoral desmoplastic stromal reaction is associated with high tumor cell dissociation in squamous cell carcinomas of the uterine cervix.

There are different types of tumoral growth patterns invading host tissue. During tumor infiltration, cancer cells not only destroy the pre-existing extracellular matrix, but usually induce new matrix formation by activating the peritumoral stromal cells; that is, desmoplastic stromal reaction (DSR) at the front of invasion (juxtatumoral stroma). This study evaluates the association between different types of invasion and DSR. Eighty-eight squamous cell carcinomas (Fédération Internationale de Gynécologie et d'Obstétrique [FIGO] stage IB to IV) were evaluated histologically for different patterns of invasion (PI) using a 3-level scoring system (pushing, finger-like, and spray-like). Desmoplastic stromal reaction was scored from none to weak, moderate, or strong. The pattern of invasion and DSR were compared with patients' age, FIGO stage, clinical tumor size, tumor grade, and the presence of lymphovascular space involvement. Finger-like PI was the most common (72.7%), followed by the spray-like PI (27.3%), whereas pushing PI was not seen. Of the tumors, 23.9% showed no DSR; 51.1%, weak; 14.8%, moderate; and 10.2%, strong DSR. Tumors with spray-like PI showed a significantly stronger desmoplastic reaction compared with the finger-like PI (P < .0001) and were significantly associated with poor tumor cell differentiation (P = .018). Moderate or strong DSR was associated with G2 and G3 carcinomas (P = .027). No correlation was seen neither for PI and DSR to lymphovascular space involvement, FIGO stage, and tumor size. The intensity of DSR, as understood in the context of a remodeling of the juxtatumoral stroma to the infiltrative tumor growth, might be indicative of a highly dissociative tumor growth and is correlated to poorly differentiated tumors.

Adult↗
PubMed2005

The bcl-2/IgH rearrangement in a population of 204 healthy individuals: occurrence, age and gender distribution, breakpoints, and detection method validity.

This study assessed prevalence, frequency, age and gender distribution and breakpoint locations, and detection method validity for the bcl-2/IgH rearrangement in 204 healthy individuals. For this purpose, both classic two-step, nested, semi-quantitative PCR as well as a newly established sequence-specific, hybridization probe-based real-time quantitative PCR (RQ-PCR) were employed and tested for their sensitivity and specificity for detecting t(14;18) positive cells in healthy blood donors. Interestingly, almost a quarter (24%; 39/204) of all healthy individuals carried the translocation, confirming data of one large prior report [Summers KE, Goff LK, Wilson AG, Gupta RK, Lister TA, Fitzgibbon J. Frequency of the Bcl-2/IgH rearrangement in normal individuals: implications for the monitoring of disease in patients with follicular lymphoma. J Clin Oncol 2001;19(2):420-4]. Regarding presence as well as frequency of the translocation, no correlation to age (mean frequency 2.0:10(4), with a median of or=40 years) nor gender was detected. Comparing the two PCR approaches, a 95.1% concordance (194/204) regarding t(14;18) detection was determined for nested and RQ-PCR, with nested PCR being slightly more sensitive (reproducible detection limit l:10(5) cells versus 1:10(4); maximum detection limit l:10(6) versus 1:10(5)). Sequence analysis confirmed individual breakpoints for all samples analyzed (29/29), indicating detection validity for both PCR approaches and ruling out contamination. The breakpoint location distribution pattern appeared to be comparable to the pattern seen with follicular lymphoma (FL) patient collectives. In conclusion, clonal bcl-2/IgH rearrangements are indeed a very frequent observation in healthy individuals, and appear to be independent of age and gender in regard to presence and frequency. This represents a conflicting finding in context of potential biological significance, and presents a potential disruptive factor for minimal residual disease (MRD) monitoring in FL patients. Prospective future trials will have to clarify the biological significance of this important observation.

Adolescent↗