The overall role of a proficiency testing program

Proficiency testing programs provide many benefits to participant laboratories, functioning as an integral component of total quality control, as a vehicle for self-improvement, as a mechanism for continuing education, and as a fulfillment of regulatory requirements. Proficiency testing should not be utilized as the sole indicator of acceptable laboratory performance; unacceptable results should serve as a trigger for further inquiry and corrective action as indicated. A proficiency testing program should be a broad-based program covering the usual spectrum of laboratory disciplines without commercial bias and it should possess continuous scientific input so as to be capable of adjusting promptly to technologic advancements as well as maintaining established participant benefits. It is important that proficiency testing programs continue to develop mechanisms of mutual interchange with accreditational bodies and regulatory agencies.     

Bony observations of some morphological variations and anomalies of the craniovertebral region

Human skeletons (214) belonging to a South African black and white cadaver population were pooled and examined for malformations of the craniovertebral region. Four crania, presenting with various manifestations of an occipital vertebra, such as a paracondylar process, epicondylar process, hypocondylar arch, and a third condyle were identified as well as two crania showing various degrees of assimilation of the atlas to the basicranium. Of particular interest was the identification of a cloverleaf-shaped foramen magnum in a cranium of an individual with achondroplasia as well as a cranium with marked asymmetry of both foramen magnum and occipital condyles. Due to the availability of both cranium and corresponding atlanto-axial components, the clinical significance of certain aspects of craniovertebral anomalies were vividly demonstrated, such as a pseudarthrosis formed by the meeting of a paracondylar process with an epitransverse process and a dens "riding high" in the foramen magnum as a result of assimilation of the atlas.     

Immunology of atopic eczema: overcoming the Th1/Th2 paradigm

Atopic eczema (AE) is a challenge for modern medicine, because it is prevalent, severely affects quality of life of patients and their families, and causes high socioeconomic costs. The pathogenesis of AE is complex. While initial studies suggested a Th2 deviation as primary reason for the disease, numerous studies addressed a genetically predetermined impaired epidermal barrier as leading cause in a subgroup of patients. Recently, immune changes beyond the initial Th2 concept were defined in AE, with a role for specialized dendritic cells as well as newly identified T helper cell subsets such as Th17 and Th22 cells. Furthermore, trigger factors are expanded beyond classical Th2 allergens such as pollen or house dust mites to microbial products as well as self‐antigens. This review pieces together our current understanding of immune as well as barrier abnormalities into the pathogenesis mosaic of AE.     

Increased expression of decorin during the regeneration stage of mdx mouse

Satellite cells exist in postnatal muscle tissue and constitute the main source of muscle precursor cells for growth and repair. These cells carry out important roles for skeletal muscle formation postnatally during growth of muscle mass as well as damage-induced regenerative processes. Muscle regeneration supports muscle function in aging and has a role in the functional impairment caused by progressive neuromuscular diseases. Major substances controlling this process are growth factors and extracellular matrix. Myostatin, a member of TGF-β family, was mainly expressed in muscle tissue. Decorin, a member of the small leucine-rich proteoglycan gene family, is composed of a core protein and a dermatan/chondroitin sulfate chain. Recent studies have shown that decorin enhanced the proliferation and differentiation of myogenic cells by suppressing myostatin activity. Thus, decorin appears to be a new molecule in the myostatin signaling pathway and a promising target for treatment of progressive neuromuscular diseases. Therefore, in this study, we examined the localization of decorin as well as myostatin in a muscular dystrophy model in mdx mice and B10 Scott Snells mice as a control to elucidate the differences between decorin and myostatin messages as well as protein distribution. This study revealed increased expression of decorin protein as well as mRNA at the regenerative stage of mdx mice compared to early stages, while only weak expression of decorin was detected in the control mice. Our study contributes to identifying the relationship between decorin and myostatin as well as the development of a therapeutic strategy for progressive neuromuscular diseases.     

The clinical manifestations of Degos' syndrome

Pathologic mechanisms underlying Degos' syndrome are poorly characterized. Thrombosis, either as a consequence of a postulated vasculitis or as a primary defect, is often a clinical complication of this syndrome. We have studied multiple coagulation parameters, including potential defects in fibrin assembly and other adhesive proteins, in a patient with Degos' syndrome and found no specific abnormality to explain the pathologic features of this syndrome. An extensive literature review as well as detailed biochemical and biophysical coagulation studies are presented. The alternative possibility of Degos' syndrome as a mucinosis is discussed.     

Interstitial 9q deletion. A primary change in a case with splenomegaly of unknown origin.

In a case with splenomegaly of unknown origin and features of hypersplenism, an interstitial 9q deletion was identified as a sole clonal abnormality of bone marrow cells. The meaning of 9q deletion as a primary change, as well as its clinical significance, are considered.     

Coronary heart disease, chronic inflammation, and pathogenic social hierarchy: a biological limit to possible reductions in morbidity and mortality

We suggest that a particular form of social hierarchy, which we characterize as "pathogenic", can, from the earliest stages of life, exert a formal analog to evolutionary selection pressure, literally writing a permanent developmental image of itself upon immune function as chronic vascular inflammation and its consequences. The staged nature of resulting disease emerges "naturally" as a rough analog to punctuated equilibrium in evolutionary theory, although selection pressure is a passive filter rather than an active agent, like structured psychosocial stress. Exposure differs according to the social constructs of race, class, and ethnicity, accounting in large measure for observed population-level differences in rates of coronary heart disease across industrialized societies. American Apartheid, which enmeshes both majority and minority communities in a social construct of pathogenic hierarchy, appears to present a severe biological limit to continuing declines in coronary heart disease for powerful as well as subordinate subgroups: "Culture"--to use the words of the evolutionary anthropologist Robert Boyd--"is as much a part of human biology as the enamel on our teeth".     

VERIDICAL AND FALSE MEMORIES IN HEALTHY OLDER ADULTS AND IN DEMENTIA OF THE ALZHEIMER'S TYPE

Five groups of participants (young, healthy old, healthy old-old, very mild Dementia of the Alzheimer's Type, Mild Dementia of the Alzheimer's Type) studied and were tested on six 12-item lists of words selected from the DRM (Deese, 1959; Roediger & McDermott, 1995) materials. These lists of words strongly converged semantically on a nonpresented critical word. The results indicated that both veridical recall and recognition performance decreased both as a function of age of the participants and as a function of dementia severity. However, the recall and recognition of the highly related nonpresented items actually increased as a function of age, and only slightly decreased as a function of DAT. When false memory was considered as a proportion of veridical memory, there was a clear increase as a function of both age of the participants and as a function of disease severity. The results are discussed in terms of (a) age and DAT-related changes in attention and memory performance, and (b) the underlying mechanisms that produce false memories in the DRM paradigm.     

The pathology of the tuberculosis 100 years ago and its present role in mortality

On occasion of the centenary of the detection of the tubercle bacteria by Robert Koch we try to give a survey on the knowledge of pathology of tuberculosis 100 years ago. Besides mystic considerations since the antique medicine, the cause of the tuberculosis was seen in a phthisic habitus, as endogenous, not perceptible, the disease as not curable, its nature as a hereditary illness, as a metabolic disorder or, in the time of Robert Koch, mostly as a malignant neoplasia. Only few physicians considered the tuberculosis as an infectious disease with inflammatory properties. Since his discovery of the tubercle bacteria, Robert Koch was sure that the tuberculosis could be cured and eradicated like other infectious diseases. He believed that this aim could be attained in a short period. At the end of this paper, a brief review is given about the frequency and importance of the tuberculosis as a cause of death in the past and especially nowadays after the consequent fight against this disease.     

HMGB1 preconditioning: therapeutic application for a danger signal?

High mobility group box 1 (HMGB1) is a nuclear factor released extracellularly as a late mediator of lethality in sepsis and as an early mediator of inflammation following injury. In contrast to the proinflammatory role of HMGB1, recent evidence suggests beneficial applications of HMGB1 in injury states. One such application is the use of HMGB1 as a preconditioning stimulus. Preconditioning is a phenomenon whereby a low level of stressful stimuli confers protection against subsequent injury. Preconditioning has been demonstrated in multiple species, can be induced by various stimuli, and is applicable in different organ systems. Only with the recent introduction of the concept of endogenous molecules, such as HMGB1, as signals and mediators for inflammation during injury states has the use of endogenous molecules been investigated for this use. This review will focus on the use of endogenous molecules, specifically HMGB1, as a preconditioning stimulus and its mechanism of protection, as well as other protective applications for HMGB1.     

Unpleasant Bodily Odour in a Psychoanalytic Treatment: Bridge or Drawbridge to a Troubled Past?

In this paper, I explore the topic of primitive bodily communications and countertransference enactments, with a particular focus on the part played by bodily odour. To explore this topic, I discuss a two-year treatment with a patient who presented with a mix of borderline and narcissistic diagnostic features. I describe meaningful aspects of the difficulties faced in countertransference work when receiving and making sense of the patient's use of primitive defences and I highlight their expression through a very uncomfortable symptom: an extremely unpleasant bodily smell. My thesis is that the smell communicated preverbal and unsymbolized experiences of early physical and emotional neglect, as well as evacuating the toxicity of those experiences. In this way the smell acted both as a bridge, which could help me reconstruct my patient's early traumatic past, and as a drawbridge, to keep me at distance and maintain his past dissociated. The invasive and aversive nature of the smell can also be seen as representing the approach-avoidance dilemma typical of a disorganized attachment state of mind, acting both as a bridge and as a drawbridge to attachment and relating.     

The importance and purpose of medical psychology in the study of medicine

Medical psychology is to be understood both as an interdisciplinary science, orientated to the bio-psychosocial concept of illness as well as a basic medical attitude that encompasses the whole of a doctor's activity. In the curriculum the students must be provided with a medico-psychological training that is specific to individual phases of study. This requires a didactic process that is centered on the student, both in the teaching of medical psychology as well as in medico-psychological hospital practice, which is to be achieved in close cooperation with other medical subjects. Medical psychology is mostly described as a newer scientific discipline. It does have a history, however, that has evolved over time. Although medical psychology has always been a building block in the thinking and actions of the medical profession, it is now explicitly anchored in the training (i.e. in the curriculum) of doctors.     

Anti-cancer immune response mechanisms in neoadjuvant and targeted therapy

Several studies suggest that the progression of malignant tumors as well as the response to chemotherapy and targeted therapy is critically dependent on the immunological parameters that are derived from the host immune system as well as a modulation of the immune system by therapeutic antibodies. It has been shown for many tumor types that the presence of a lymphocytic infiltrate in different types of cancers is a positive factor for clinical outcome and that the response to neoadjuvant chemotherapy is increased in a tumor with a prominent pretherapeutic infiltrate. Furthermore, new targeted therapies in breast cancer, such as trastuzumab, as well as in hematological malignancies, such as rituximab and alemtuzumab, have been shown to interact with immunological pathways, and this interaction is critical for response and clinical outcome. In neoplasms of lymphoid and hematopoietic tissues, targeted therapies not only reduce toxic effects on normal tissues but also lead to modulations of the immune system depending on the target molecule, its physiological function and cellular distribution. This review gives an overview on clinical data on response to classical chemotherapy as well as molecular targeted therapy and its interaction with the immune system.     

Addressing the potential toxicities of the non-specific P-glycoprotein modulation by amalgamation with targeted approach in MDR tumors

Multidrug resistance (MDR) is an area of concern for the drug developers as well as clinical practitioners. This phenomenon is putting an emance pressure on treatment modalities of many diseases as well as posing a grave danger over clinically accepted drugs as well as molecules under clinical development. P-glycoprotein (P-gp) mediated efflux of xenobiotics is one of the major mechanisms involved in MDR. Hence, an effective modulation of P-gp may restore the potential of many substrate drugs. However, the non-specific P-gp modulation may be associated with many unwanted toxic effects. Therefore, an approach involving simultaneous exploitation of P-gp modulation as well as targeted delivery in a particulate carrier system may result in a more effective MDR reversal, accompanying a safer drug profile.     

Streptococcal meningitis resulting from contact with an infected horse

We report a case of group C streptococcal meningitis in a woman with a history of close animal contact as well as head trauma as a result of a kick by a horse. Blood and cerebrospinal fluid cultures grew Streptococcus equi subsp. zooepidemicus, as did a throat culture taken from the colt that had kicked her 2 weeks prior to admission.     

Silicon carbide: a versatile material for biosensor applications

Silicon carbide (SiC) has been around for more than 100 years as an industrial material and has found wide and varied applications because of its unique electrical and thermal properties. In recent years there has been increased attention to SiC as a viable material for biomedical applications. Of particular interest in this review is its potential for application as a biotransducer in biosensors. Among these applications are those where SiC is used as a substrate material, taking advantage of its surface chemical, tribological and electrical properties. In addition, its potential for integration as system on a chip and those applications where SiC is used as an active material make it a suitable substrate for micro-device fabrication. This review highlights the critical properties of SiC for application as a biosensor and reviews recent work reported on using SiC as an active or passive material in biotransducers and biosensors.     

Hospital as a temple

The present concept of hospital health care has exhausted its purpose. In a personal view as well as experience the idea "Hospital as a temple" was studied in an attempt to reconcile modern and technical with older form of health care, the latter often labelled as alternative or complementary. Both from a historical perspective as well as nowadays situation this vision is pursued.     

Thermosensitivity of N-isopropylacrylamide hydrogels cross-linked with degradable cross-linker

Thermosensitive N-isopropylacrylamide (NIPA)-based hydrogels have been prepared using a biodegradable pseudo-peptide (DMTLT, a tri-molecular adduct of tyrosine, lysine, tyrosine) as cross-linker. This new cross-linker provides a similar cross-linking efficiency as N,N' methylenbisacrylamide (BIS) (a standard biostable cross-linker) used as reference. The amount of DMTLT has shown to modulate, in addition to the cross-linking density, the transition temperature (the higher the amount of DMTLT, the lower the transition temperature), as well as the morphology and the whole aqueous behaviour. The incorporation of hydrophilic N,N'-dimethylacrylamide (DMA) increases the transition temperature, as expected. Finally, the matrices have exhibited in aqueous media a well-defined pulsatile behaviour in swelling and release of benzoic acid and dextran as models of ionisable molecules and non-ionisable macromolecules.     

The effect of immunosuppressive and anti-inflammatory drugs on lymphocyte population and MIF in glomerulonephritis.

The effect of immunosuppressive and anti-inflammatory drugs on the T and B lymphocyte populations, as well as cellular hypersensitivity in relation to GBM antigens (measured by MIF activity) in 60 patients with different types of glomerulopathy has been tested. The results were compared with a control group of 47 untreated patients and 32 healthy subjects. The treatment was carried out using the following drugs: azathioprine, cyclophosphamide, prednisone, ibuprofen and indomethacin. In a sample of 14 patients receiving ibuprofen and in 7 receiving arathioprine, indomethacin and prednisone, the T and B lymphocyte kinetics as well as MIF activity were repeatedly tested before and during the treatment of 150 days. In the patients under this treatment, a decreased percentage of lymphocytes with receptors for a complement as well as, in some cases. MIF suppression was observed. A comparison of healthy subjects and untreated patients with a group of 39 subjects tested for T and B lymphocytes as well as MIF activity after several months of the above treatment was made. It was found that supportive therapy with azathioprine and prednisone led to a normalization of B lymphocytes (EA and EAC rosettes) and to a small increase of T lymphocytes number. On the other hand, treatment with indomethacin and ibuprofen led to an increased B lymphocyte count (EA and EAC rosettes). Cyclophosphamide given with azathioprine caused a decrease in the proportion of T lymphocytes and an increase in the number of null cells. In addition, it was found that immunosuppressive drugs as well as anti-inflammatory drugs, even when administered in supportive doses caused in some cases, the suppression of cellular immunity as measured by MIF activity.