Über den möglichen Einfluß plasmatischer Faktoren auf die lymphozytäre Stimulierbarkeit und E-Rosetten-Bildung bei primär chronischer Polyarthritis

Zusammenfassung Es wurde in vitro an 51 Patienten mit chronischer Polyarthritis die lymphozytäre Blastogenese zu PHA in Kulturen mit autologem oder normalem Plasma sowie auch die E-Rosetten-Bildung und die Gegenwart an Oberflächen-Ig untersucht. Während der Prozentsatz an T- und B-Zellen fast normal bleibt (52,1±2,1% und 18,1±2,1%, n.W. 55,6±2,0% und 16,2±0,8%), ist die Blastogenese in den Kulturen mit 25% autologem Plasma (5 399±709 cpm gegen dem Standartwert von 13 182±920 cpm) bedeutend verringert. Diese kehrt fast zu den Normalwerten zurück, sobald man das Patientenplasma mit Plasma von Gesunden ersetzt (12 189±1 081 cpm). Das rheumatoide Plasma ist imstande die Blastogenese von 11 normalen Personen zu hemmen (7 395±750 cpm). Eine vorhergehende Inkubation für 90 der Lymphozyten von 14 Kontrollpersonen in rheumatoidem oder autologem Plasma führt zu einer bedeutenden Differenz in der E-Rosettenbildung (40,8±1,4% und 56,2±2,1%). Dies bedeutet das die funktionelle Hemmung der T-Lymphozyten bei dieser Krankheit auf plasmatische Faktoren zurückzuführen ist.     

An experimental study on the neurotoxicity of n-hexane metabolites: Hexanol-1 and hexanol-2

n-Hexane is a solvent causing peripheral neuropathies. On several occasions it has been postulated that it may act via metabolic products. Therefore, the neurotoxicity of hexanol-1 and hexanol-2, hexane's principal metabolites, was studied. The compounds were given to rats ip for 8 months. Hexanol-1 produced equivocal signs of neurotoxicity in the peripheral nervous system. Hexanol-2 caused a peripheral neuropathy verified both neurophysiologically and histologically. This neuropathy was similar to those observed in experimental polyneuritis due to n-hexane, methyl n-butyl ketone, and 2,5-hexanedione. Hexanol-2 may therefore be considered as a neurotoxic product connecting the metabolic pathways of n-hexane and methyl n-butyl ketone.     

T-lymphocyte subpopulations in chronic lymphocytic leukemia: a quantitative and functional study

In the peripheral blood of patients with chronic B-cell lymphocytic leukemia (B-CLL) absolute numbers of E-rosetting lymphocytes were increased. The proportions of TG and TM cell subsets were analyzed, as were their effects on the pokeweed mitogen (PWM)-dependent differentiation of normal allogenic B cells or of autologous leukemic cells. The TG lymphocyte subset was further studied for its cytotoxic activity in antibody-dependent cellular cytotoxicity (ADCC). A marked increase both in percentages and in absolute numbers of TG cells was found. TM lymphocytes percentages were normal, but because of the T lymphocytosis occurring in all patients, the absolute numbers of TM were increased. TM and TG subsets showed helper and suppressor activity, respectively, in PWM-induced B-cell differentiation. TG cells displayed effector cell activity in ADCC. The results provide further evidence that T lymphocytes from patients with B-CLL are functionally normal. However, a noticeable increase of the T-cell subset having suppressor and cytotoxic activity in ADCC was observed. This may be the consequence of a normal immune reaction to the leukemic population.     

Persistent polyclonal lymphocytosis in human immunodeficiency virus-1- infected patients

In this study we describe the clinical, morphologic, immunologic, and genetic features of a chronic peripheral blood lymphocytosis associated with posttraumatic splenectomy in patients with human immunodeficiency virus-1 (HIV-1) infection. Among a series of 2,365 consecutive HIV-1 seropositive cases investigated, eight patients were selected for the presence of more than 4,000 lymphocytes/mm3. All cases were characterized by a lymphocytosis with cytoplasmic azurophilic granules; in three patients the hematologic picture was superimposable with that of lymphoproliferative disease of granular lymphocytes. Phenotypic analysis of lymphocytes showed a prevalent CD3+CD8+ pattern. In vitro evaluations, including the response to mitogens and interleukin-2 and the cytotoxic assays, showed an unimpaired lymphocyte function in the majority of our patients, even in those with advanced stages of the syndrome. The analysis of the configuration of the T-cell receptor (TCR) beta and gamma genes showed a polyclonal pattern of rearrangement. At the mean follow-up time of 45 +/- 8 months, one patient died of overdose when the clinical conditions were stable; all the other patients are alive, although disease progression was documented in two. Our results indicate that a chronic polyclonal lymphocytosis may be associated with HIV-1 infection; this finding seems to be restricted to patients who have undergone splenectomy. The demonstration of a still uncompromised immune system together with a silent clinical course in the patients under study also suggest that splenectomy per se does not favor an aggressive clinical behavior of HIV-1 infection.     

Hemofiltration With the Cascade System in an Experimental Porcine Model of Septic Shock

Abstract: High-volume hemofiltration (HVHF) has been suggested as an adjuvant treatment of septic shock because of its capacities to remove inflammatory mediators from blood. Nevertheless, HVHF presents some important drawbacks, such as the depletion of low molecular weight molecules (nutriments, vitamins, trace elements and antibiotics) due to the high ultrafiltration rate, or the significant financial cost and nursing workload due to the frequent changes of large amounts of expensive sterile substitution fluids. A new hemofiltration system called “Cascade” has been developed, allowing very high ultrafiltration rates (120 mL/kg/h) limiting these drawbacks by using a special extracorporeal circuit. The objective of this study was to assess the technical feasibility of the Cascade system and to compare its hemodynamic impact to that of the standard HVHF system. Twenty sepsis-induced pigs were randomized in two groups: one group was hemofiltered with the standard HVHF system and the other with the Cascade system during a six-hour session. No technical problems were observed with the Cascade system during the experiment. At the end of the experiment, colloid requirements (989 ± 355 mL vs. 1913 ± 538 mL, P = 0.006), epinephrine requirements (0.82 ± 0.42 mg vs. 3.27 ± 3.02 mg, P < 0.001), lactic acidosis (pH = 7.33 ± 0.08 vs. 7.10 ± 0.07, P < 0.001) and mean pulmonary arterial pressure were less pronounced in the Cascade group. These results suggest that Cascade hemofiltration is technically feasible and safe. Moreover, compared with standard HVHF, it can reduce the severity of porcine septic shock.     

AMINOXY ANALOGS OF LEU-ENKEPHALIN

Seven analogs of Leu-enkephalin where an aminoacid is replaced by an aminoxy-acid (aminoxy-acetic, or L- or D-aminoxy-phenylpropionic or 2-aminoxy-4-methylvaleric) have been synthesized. Only analogs bearing the α-aminoxy-acid at position 5 have biological activity in vitro.     

Perspectives on Intravenous Oxycodone for Control of Postoperative Pain

Intravenous (IV) analgesia has particular advantages in the immediate postoperative period. For example, IV administration results in a faster onset of pain relief and results in more predictable pharmacokinetics than does administration by other routes. It also allows for convenient dosing before or during surgery, permitting the initiation of effective analgesia in the early phase of the postoperative period. In addition, when patients are able to tolerate oral intake, they can be switched from IV to oral dosing based on maintaining the predictable analgesia established by the IV route. IV morphine is widely used for the control of postoperative pain, but there is a trend toward the use of oxycodone. Oxycodone (which may be mediated partly through kappa‐ as well as mu‐opioid receptors) offers several potential advantages. Published studies comparing IV oxycodone to other IV opioids for postsurgical pain report that oxycodone is a safe and effective analgesic. Some studies show that IV oxycodone may be associated with greater pain control, fewer or less severe adverse events, and faster onset of action, although the results are not consistent across all studies. Oxycodone has been reported to be safe in the geriatric and other special populations when adequate clinical adjustments are made. Thus, the clinical reports and oxycodone's pharmacologic profile make intravenous oxycodone a potentially important “new” old drug for postoperative pain control.