Epidemiology and antifungal resistance in invasive Aspergillosis according to primary disease: review of the literature.

Aspergilli, less susceptible to antifungals emerge and resistance to azoles have been found mainly in Aspergillus fumigatus; this has launched a new phase in handling aspergillosis. Resistant strains have currently been reported from Belgium, Canada, China, Denmark, France, Norway, Spain, Sweden, The Netherlands, UK and the USA. Centres in the UK (Manchester) and The Netherlands (Nijmegen) have described particularly high frequencies (15 and 10% respectively), and a significant increase in azole resistance in recent years. The reason of this high incidence may be due to long term azole therapy in patients with chronic aspergillosis in Manchester, and due to high use of agricultural azoles in Nijmegen. The primary underlying mechanism of resistance is as a result of alterations in the cyp51A target gene, with a variety of mutations found in clinical isolates and one genotype identified in the environmental (LH98). Reports on well documented in vitro and in vivo resistance to echinocandins are rare for Aspergillus species and resistance may be under-diagnosed as susceptibility testing is less frequently performed due to technical reasons.

[ARMOR: an electromechanical robot for upper limb training following stroke. A prospective randomised controlled pilot study]. / ARMOR: Elektromechanischer Roboter für das Bewegungstraining der oberen Extremität nach Schlaganfall. Prospektive randomisierte kontrollierte Pilotstudie.

PURPOSE: Due to the complexity of the upper motor neuron syndrome, functional improvement in the paretic upper limb after stroke continues to be a challenge in neurorehabilitation. Robot-assisted training has been shown to be useful in relearning gait. In order to achieve similar results in the upper limb, an electromechanical arm robot (ARMOR), capable of moving all joints through complex patterns, has been developed. MATERIAL AND METHOD: Eight patients following stroke of different etiologies were included in a clinical AB-BA cross-over study comparing ARMOR training with EMG-triggered neuromuscular electrical stimulation (EMG-NMES). Chedoke-McMaster Stroke Assessment, modified Ashworth Scale, goniometry (Neutral-0-Method), dynamometry and Functional Dexterity Test served as outcome measures. RESULTS: ARMOR training resulted in more improvement of muscle tone (p = 0.004), range of movement (ROM) (p = 0.005) and dexterity, but less improvement of strength, than EMG-NMES. Chedoke-McMaster Stroke Assessment showed improvement of at least one point in shoulder pain and arm and hand activity during ARMOR training, while these values did not change with EMG-NMS. Better results of ARMOR training were achieved in the earlier phase (A1) than in the later phase (A2). CONCLUSION: This study demonstrates the positive effect of automatised training with a new electromechanical arm robot (ARMOR), and documents its clinical applicability in the rehabilitation of the paretic upper extremity in stroke patients.

Effects of norepinephrine and phenylephrine on intestinal oxygen supply and mucosal tissue oxygen tension.

OBJECTIVES: To investigate effects of intravenous norepinephrine (NE) and phenylephrine (PE) on intestinal oxygen supply in an autoperfused, innervated jejunal segment. DESIGN AND SETTING: Prospective, randomized animal study in an animal research laboratory. MATERIALS AND METHODS: In 24 anesthetized and normoventilated pigs a segment of the jejunal mucosa was exposed by midline laparotomy and antimesenteric incision. Mucosal oxygen tension (PO2muc; Clark-type surface oxygen electrodes), microvascular hemoglobin oxygen saturation (HbO2, tissue reflectance spectrophotometry), and microvascular blood flow (perfusion units, PU; laser Doppler velocimetry), systemic hemodynamics, mesenteric-venous acid base and blood gas variables, and systemic acid base and blood gas variables were recorded after a resting period and at 20-min intervals during infusion of NE (0.01, 0.05, 0.1, 0.5, 1, 2 micrograms x kg-1 x min-1; n = 8) or PE (0.1, 0.5, 1, 2, 5, 10 micrograms x kg-1 x min-1; n = 8) and in controls (n = 8) without treatment. RESULTS: NE infusion led to significant tachycardia, an increase in cardiac output, and systemic oxygen delivery and consumption while PE progressively increased mean arterial pressure with only small effects on systemic blood flow. NE or PE infusion did not affect mesenteric venous oxygen tension (baseline: PE 53 +/- 5, NE, 52 +/- 4.2 mmHg), mesenteric oxygen extraction ratio (baseline: PE 0.29 +/- 0.08, NE 0.3 +/- 0.06), jejunal microvascular blood flow (baseline: PE 254 +/- 127, NE 282 +/- 72 PU), PO2muc (baseline: PE 31 +/- 9.1, NE 33 +/- 11 mmHg), and HbO2 (baseline: PE 52 +/- 9.6%, NE 58 +/- 11.6%). CONCLUSION: Despite major differences in systemic hemodynamics jejunal tissue oxygen supply is not affected by progressively increasing intravenous infusion of norepinephrine and phenylephrine.

Effects of epinephrine on intestinal oxygen supply and mucosal tissue oxygen tension in pigs.

OBJECTIVE: To study the effects of increasing dosages of epinephrine given intravenously on intestinal oxygen supply and, in particular, mucosal tissue oxygen tension in an autoperfused, innervated jejunal segment. DESIGN: Prospective, randomized experimental study. SETTING: Animal research laboratory. SUBJECTS: Domestic pigs. INTERVENTIONS: Sixteen pigs were anesthetized, paralyzed, and normoventilated. A small segment of the jejunal mucosa was exposed by midline laparotomy and antimesenteric incision. Mucosal oxygen tension was measured by using Clark-type surface oxygen electrodes. Microvascular hemoglobin oxygen saturation and microvascular blood flow (perfusion units) were determined by tissue reflectance spectrophotometry and laser-Doppler velocimetry. Systemic hemodynamics, mesenteric-venous acid-base and blood gas variables, and systemic acid-base and blood gas variables were recorded. Measurements were performed after a resting period and at 20-min intervals during infusion of increasing dosages of epinephrine (n = 8; 0.01, 0.05, 0.1, 0.5, 1, and 2 microg x kg(-1) x min(-1)) or without treatment (n = 8). In addition, arterial and mesenteric-venous lactate concentrations were measured at baseline and at 60 and 120 mins. MEASUREMENTS AND MAIN RESULTS: Epinephrine infusion led to significant tachycardia; an increase in cardiac output, systemic oxygen delivery, and oxygen consumption; and development of lactic acidosis. Epinephrine significantly increased jejunal microvascular blood flow (baseline, 267 +/- 39 perfusion units; maximum value, 443 +/- 35 perfusion units) and mucosal oxygen tension (baseline, 36 +/- 2.0 torr [4.79 +/- 0.27 kPa]; maximum value, 48 +/- 2.8 torr [6.39 +/- 0.37 kPa]) and increased hemoglobin oxygen saturation above baseline. Epinephrine increased mesenteric venous lactate concentration (baseline, 2.9 +/- 0.6 mmol x L(-1); maximum value, 5.5 +/- 0.2 mmol x L(-1)) without development of an arterial-mesenteric venous lactate concentration gradient. CONCLUSIONS: Epinephrine increased jejunal microvascular blood flow and mucosal tissue oxygen supply at moderate to high dosages. Lactic acidosis that develops during infusion of increasing dosages of epinephrine is not related to development of gastrointestinal hypoxia.

[Interactions between the immune system and the psyche]. / Interaktionen zwischen Immunsystem und Psyche.

Compared to well documented studies on immunosuppression "psychologically induced immunoenhancement" is a rather neglected topic in medical literature and research, even in the new established field of psychoneuroimmunology. Starting with the premise that research questions emanating from this field and from behavioural medicine may provide critical information for understanding the phenomena of immunomodulation, evidence and illustrations of psychologically induced immunoenhancement are provided in the context of psychosocial neuroimmunomodulation. Distress-reducing interventions such as progressive relaxation training, imagery, experimentally induced short-term positive mood states and mirthful laughter enhances various aspects of immune functions, i.e., primarily the phylogenetically old paraspecific parameters. Additionally, a larger variety of emotional/psychosocial factors with potentially but yet unproved immunoenhancing effects seems to exist. In particular, enhancement of phagocytosis, NK cell and T cell response to phytohemagglutinin, decrease in the number of suppressor/cytotoxic T cells and increase in the number of circulating T helper/inducer cells in peripheral blood, and enhancement of spontaneous lymphocyte blastogenesis as well as cytokines have all been shown to be associated with the above mentioned intervention techniques.

[Health and disease in humans and animals over the course of history]. / Gesundheit und Krankheit bei Mensch und Tier im Wandel der Zeit.

A historical review of the terms health and sickness in human beings and animals. The terms health and sickness have changed from ancient history to the present day and have also been modified. The notions of what life really is, when it starts and when it ends, have contributed to these changes. Historically, health and sickness have generally been interpreted anthropocentrically in the course of time, rarely has the companionship between man and animal been taken into account. A closer look over the past three millennia as to the science of the dynamics of diseases, the humoral pathology and the solidistic pathology, leads to the conclusion that the terms sickness and health have only been understood in general, not in detail. In the last decades of the 19th century and up to the present day an essential change of the notion of sickness was initiated through cellular pathology by R. Virchow (1821-1902). Eventually, bacteriology, virology, molecular biology and gene technology have established new standards with regard to health and sickness and have paved the way to the present holistic medicine, which is based on science. Sickness is defined as a verifiable divergence from the norm of anatomical, physiological, immunological and psychic conditions of an organism and, accordingly, as a pathological form of being, implying a disturbance of homeostasis. The legal issues such as the federal laws on epidemic diseases of human beings and animals and on insurance are dealt with in conclusion.

[Recent perceptions on the development, assembly and function of the immune system]. / Neue Erkenntnisse über Entwicklung, Aufbau und Funktion des Immunsystems.

The immune system developed through many stages during evolution. It is fascinating that none of the diverse defense mechanisms vanished in such a long period of nearly 3.5 billion years. They still function in the integrated immune system. The barrier system can be compared to the immune system. The immune system itself is subdivided in antigen-independent, paraspecific (primitive immune system) and antigen specific (specific immune system), restricted immune reactions. The role and use of the phylogenetically older, paraspecific mechanisms, that will react immediately after antigen exposure, are discussed in detail. The immune system is not autonomous. It is closely linked to the hormonal, circulatory, metabolic and nervous systems. Its function is comparable to a sensory organ. Psychoneuroimmunology as a new discipline is mentioned. Immunity and paramunity are not seen as opposing phenomena but are linked in their functions. The terminology of immunology is discussed.

[Comparative studies of the paraspecific immunostimulation (paramunization) by bacterial lysates in bacterial infection models and in the cytotoxicity test]. / Vergleichende Untersuchungen über die paraspezifische Immunstimulierung (Paramunisierung) durch Bakterienlysate in bakteriellen Infektionsmodellen und im Cytotoxizittstest.

Bacterial lysates of different bacterial strains (E. coli, B. bronchiseptica, P. haemolytica) were prepared by heating, acid- and alkaline-hydrolysis. Lysates were tested for their immunostimulating effect in bacterial infection models and with chromium 51 test demonstrating spontaneous (natural) cytotoxicity. Lysate production was standardized by protein- and Lps-determination. The alkaline-hydrolysis reduced toxicity of Lps and increased the content of soluble bacterial protein. Heating and acid-hydrolysis did not alter bacterial suspensions with respect to Lps-toxicity and protein-content. Mice infected with P. aeruginosa, P. multocida, E. coli and L. monocytogenes (5-10 LD50) had a significantly longer survival time after prophylactic immunostimulation with bacterial lysates than control animals. No protection was observed in immunostimulated mice infected with Erysipelothrix rhusiopathiae. In the Pseudomonas infection model, bacterial lysates prepared by alkaline-hydrolysis had a 10 times higher immunostimulating effect than lysates prepared by acid-hydrolysis or heating. Bacterial lysates stimulated spontaneous cytotoxicity of natural mouse peritoneal killer cells after intraperitoneal application. Whole bacterial lysates had a higher NK-activity as their corresponding purified lipopolysaccharide portion.

A randomized study of combination chemotherapy (VAC-FMC) with or without immunostimulation by Corynebacterium parvum in metastatic breast cancer.

A total of 156 patients with metastatic breast cancer were entered into a prospective multi-center trial in September 1975. All patients were treated monthly with vincristine, adriamycin and cyclophosphamide (VAC) six times, followed by 5-fluorouracil, methotrexate and cyclophosphamide (FMC) until progression was documented. By random assignment, the patients received 5 mg/m2 Corynebacterium parvum (CP) subcutaneously on day 1, in addition to VAC/FMC. Of the 150 evaluable patients, 33 of 76 (45%) and 36 of 74 (49%) had complete or partial response to VAC/FMC plus CP, respectively. The Kaplan-Maier curves of duration of remission and survival were almost identical (medians 14.5 vs 12.1 months and 22.2 vs 21.1 months, respectively). The hematologic and gastrointestinal toxicity were also similar in the two study groups. However, 19 of 74 (26%) patients developed skin ulcers after repeated injections of CP. These patients showed prolonged survival (P = 0.002, log rank test). These results suggest that adding nonspecific immunostimulation with CP to currently available chemotherapy on day 1 is of no benefit to most patients with metastatic breast cancer, but may select an "immunoreactive subgroup with increased local toxicity and survival.

[Chemotherapy of gastrointestinal tumors (review of the literature)]. / Chemotherapie gastrointestinaler Tumoren (Literaturübersicht).

There exist no common recommendations for palliative therapy of gastrointestinal cancer. Fluorouracil has been used for a long time, remission rates reported range from 0% to 80%. In larger series they figure about 20% but without prolongation of survival in responders. Although this drug is used for 20 years optimal dose and timing is still unknown. By combination of fluorouracil with other drugs remission rates were improved and in responders survival was prolonged (mitomycin C and/or adriamycin in gastric cancer, methyl-CCNU in colorectal cancer). The results of adjuvant chemotherapy of gastrointestinal cancer are contradictory, the routine usage is not recommendable. Adjuvant as well as palliative chemotherapy must be improved by controlled clinical trials.

[Effect of active interferonization and anti-thymocyte globulin on the growth of virus-induced hamster melanoma A-Mel-S]. / Der Einfluss einer aktiven Interferonisierung und der Einfluss von Anti-Thymozyten-Globulin auf das Wachstum des Virus induzierten Hamstermelanoms A-Mel-S

The present data show that biological and synthetic inducers of interferon are able to reduce the growth of a transplantable malignant melanoma in the Syrian hamster. The advantage of the biological inducer H-MP are that it is not toxic for humans and that a high titer of interferon can be maintained over a long period of time.