Eosinophil differentiating activity in sera of patients with AIDS under recombinant IL-2 substitution

Summary An increase in circulating eosinophils was observed in patients with AIDS or ARC who were substituted for a period of 14 days with exogenous recombinant IL-2 in the context of a Phase I/II study. IL-2 exerts a broad range of biological properties and enhances the production of a variety of other cytokines, i.e., factors for haemopoietic cell growth and differentiation. After having excluded a direct effect of r IL-2 on haemopoietic precursor cells in semi-solid agar cultures, we developped a liquid culture system and studied the effect of patients' sera collected at different time intervals before, during and after r IL-2 substitution on cell differentiation of normal human bone-marrow cells in vitro. Patients' eosinophilia was preceded by a detectable activity in the sera which induced light-density, nonadherent bone-marrow cells to differentiate into the eosinophil lineage and was assessed by the presence of eosinophil primary granules or Luxol-fast blue positive granules. Thus, these in vitro data suggest the presence of circulating mediator(s) enhancing eosinophil production and differentiation in response to in vivo substitution of r IL-2.     

Bone marrow transplantation with unrelated donors: what is the probability of identifying an HLA-A/B/Cw/DRB1/B3/B5/DQB1-matched donor?

Patients transplanted with marrow from an HLA-ABDR serologically matched unrelated donor suffer from more post-transplant complications than those who are transplanted with marrow from an HLA-identical sibling. This is most likely due to either HLA-ABDR incompatibilities not resolved by standard techniques and/or HLA polymorphisms not tested for by routine tissue typing (HLA-Cw,-DQ). By resolving these incompatibilities by molecular techniques combined with the in vitro cytotoxic T lymphocyte precursor frequency (CTLpf) test, we have shown that a high degree of HLA compatibility is associated with increased patient survival. However, higher requirements for HLA matching decrease the number of available donors. We have estimated the probability of finding an HLA-A/B/Cw/DRB1/DRB3/DRB5/DQB1 compatible donor based on 104 consecutive unrelated bone marrow donor searches initiated between January 1995 and December 1997, with December 1998 as the endpoint. For 96 patients (92.3%), one or more ABDR-identical donors were listed in the Bone Marrow Donor Worldwide Registry (BMDW). After contacting the registries, we obtained at least one (mean, 5.36; range, 1-20; total, 461) blood sample for 86 patients. A highly compatible donor was identified for 33/86 patients (38.4%), after testing an average number of 4.5 donors/patients (range, 1-13). However, by accepting an HLA-DRB3 or -DQB1 or -Cw incompatibility, this number would be as high as 68.6%. Approximately half of the patients (n = 40) for whom a search had been initiated have been transplanted: 22 patients with a perfectly matched donor, 15 patients with an HLA-DRB3 or -DQB1 or -Cw mismatch and three with other mismatches. The average time needed to identify the most compatible donor was 4 months. Extremely long searches seemed to be less useful, because after testing the first seven, a more compatible donor was seldom found. These results show that even when requirements for compatibility are high, the chances of finding a donor remain considerably low.     

Immunohistochemical, electron microscopic and in situ hybridization evidence for the involvement of lymphatics in the spread of HIV-1

To investigate the role of the lymphatic vessels and the sinus systems of the lymph node in the spread of HIV-1, we evaluated 15 lymph nodes from patients with persistent generalized lymphadenopathy (PGL). Fifteen lymph nodes taken from patients with follicular hyperplasia not related to HIV-1 infection served as controls. Immunohistochemical and in situ hybridization techniques revealed infected cells within the sinuses and the efferent lymphatics of the PGL lymph nodes. In contrast, infected cells could not be detected within the walls of the high endothelial venules nor in the areas immediately adjacent. The parenchymal side of the marginal sinus was lined by a discontinuous endothelium. Macrophages and lymphocytes were located within the gaps of this endothelium. More importantly, when the enlarged follicle extended as far as the wall of the marginal sinus, the processes of follicular dendritic cells could be seen extending through the gaps into the lumen of the sinus. This suggests that these cells could transport antigens (including HIV-1) from the sinuses directly to the germinal centers. In addition, HIV-1 particles within cytoplasmic vacuoles were seen in infected macrophages located in the submarginal zone. Positive cells were also found in the extrafollicular lymphoid parenchyma, especially in the area between the marginal sinus and the follicles. The observed distribution of the virus-positive cells within the PGL lymph nodes strongly implicates the lymphatic vessels in the spread of HIV-1 infection.     

Attenuation of myocardial ischemia during coronary occlusion by ultrashort-acting beta adrenergic blockade.

To assess the effect of the ultrashort-acting beta blocker esmolol on ischemia induced by acute coronary occlusion, we studied 16 patients undergoing coronary angioplasty. Doppler echocardiography and ECG monitoring were performed continuously before, during, and after balloon occlusion in the drug-free state and during esmolol infusion. Fourteen of the 16 patients had ST segment elevation during balloon inflation. However, maximal ST segment elevation (2.1 +/- 1.5 mm vs 1.7 +/- 1.3 mm, p less than 0.001) and duration of ST segment elevation (68 +/- 20 seconds vs 54 +/- 19 seconds, p less than 0.05) were both significantly reduced during esmolol infusion. Furthermore, the decrease in ejection fraction seen during drug-free balloon occlusions was significantly blunted during esmolol infusion. In the baseline state ejection fraction decreased from 55% to 38% (p less than 0.05) during coronary occlusion compared with a decrease from 52% to 49% (p = NS) during esmolol infusion. In addition, esmolol appeared to delay the onset of segmental wall motion abnormalities after coronary occlusion, occurring at a mean of 40 seconds after balloon inflation versus a mean of 31 seconds in the absence of beta blockade (p less than 0.05). Thus the use of ultrashort-acting beta blockade appears to diminish the extent and delay the onset of myocardial ischemia during acute coronary occlusion.     

Coronary angiography using 4 Fr catheters with acisted power injection: A randomized comparison to 6 Fr manual technique and early ambulation.

Coronary angiography using 4 Fr catheters may reduce access site complications, promote better utilization of outpatient facilities, but at a cost of suboptimal image quality. To determine whether 4 Fr diagnostic angiography with power injection (Acist, Minneapolis, MN) was equivalent to 6 Fr manual technique, 101 unselected patients were randomized to transfemoral coronary angiography with 4 or 6 Fr catheters. Procedural characteristics, angiographic quality scores, and results of 90 min ambulation were analyzed. Coronary angiographic quality scores using 4 Fr and 6 Fr catheters were equivalent (left coronary artery 4.73 +/- 0.6 vs. 4.80 +/- 0.65, P = 0.28; right coronary artery 4.98 +/- 90.13 vs. 4.97 +/- 0.16, P = 0.48). However, 4 Fr left ventriculographic image score was lower (4.53 +/- 0.68 vs. 4.83 +/- 0.42, P = 0.0002), attributed, in part, to a smaller injected contrast volume (32 +/- 11 vs. 37 +/- 4 mL, P = 0.001). The total study contrast volume was significantly less in the 4 Fr group (119 +/- 35 vs. 159 +/- 52 mL, P = 0.001). Complications related to early ambulation at 90 min were similar and minimal in both groups. Compared to 6 Fr manual contrast injection technique, diagnostic angiography through 4 Fr catheters with power contrast injection resulted in equivalent coronary angiographic image quality, slightly reduced but diagnostic left ventricular image quality, and significantly less contrast volume. Four Fr angiography facilitates early ambulation without compromising safety and image quality.     

Ofloxacin for prevention of bacterial infections in granulocytopenic patients

Summary We studied the potential value of oral ofloxacin (200 mg twice daily) for selective decontamination and infection prevention in 40 granulocytopenic patients with acute leukemia, blast crisis of chronic myelogenous leukemia, hairy cell leukemia or severe aplastic anemia. The quality of selective decontamination was acceptable with rapid elimination of Enterobacteriaceae from the alimentary tract, only a slight decrease in concentrations of anaerobes in faeces, and a small number of newly acquired transient (twelve isolates in seven patients) or colonizing (six strains with 28 isolates in four patients) aerobic gram-negative rods andStaphylococcus aureus (one isolate) recovered from 672 surveillance cultures from faeces, oral washings and urine. Two of three patients colonized with ofloxacin-resistantPseudomonas aeruginosa strains developed Pseudomonas infections. A total of twelve acquired infections was observed. Six were microbiologically documented infections, all caused by ofloacin-resistant bacteria (twoP. aeruginosa, twoStaphylococcus epidermidis, oneAerococcus viridans, oneMicrococcus sp.). Tolerance was acceptable with no serious side effects observed. Mean drug concentrations in serum and saliva were comparable to those determined in healthy volunteers and were found to be higher in saliva than in serum. We conclude that ofloxacin may be studied as an effective alternative to trimethoprim-sulfamethoxazole for selective decontamination and infection prevention in severely granulocytopenic patients. Careful monitoring of colonizingPseudomonas spp. with decreased ofloxacin sensitivity, however, seems necessary.

---

Prophylaxe bakterieller Infektionen durch Ofloxacin bei granulozytopenischen Patienten

Zusammenfassung Der Wert einer Behandlung mit Ofloxacin (2 × 200 mg täglich) für die sogenannte selektive Dekontamination und Infektionsprophylaxe bei Granulozytopenie wurde bei 40 Patienten mit akuter Leukämie, akuter Phase einer CML, Haarzell-Leukämie oder schwerer aplastischer Anämie untersucht. Es kam zu einer akzeptablen Qualität der selektiven Dekontamination mit Elimination von Enterobacteriaceae in der Darmflora und einer nur geringen Verringerung in der Anaerobier-Konzentration im Stuhl. Die Auswertung von 672 Überwachungskulturen aus Rachenspülung, Stuhl und Urin zeigte eine kleine Zahl von neu entdeckten transienten (zwölf Isolate bei sieben Patienten) oder kolonisierenden (sechs Stämme mit 28 Isolaten bei vier Patienten) aeroben gramnegativen Bakterien und vonStaphylococcus aureus (ein Isolat). Zwei von drei Patienten mit Nachweis von kolonisierenden Ofloxacin-resistentenPseudomonas aeruginosa entwickelten Pseudomonas-Infektionen. Insgesamt wurden zwölf erworbene Infektionen beobachtet, davon sechs mikrobiologisch dokumentierte Infektionen, die alle durch Ofloxacin-resistente Erreger hervorgerufen wurden (zweiP. aeruginosa, zweiStaphylococcus epidermidis, einAerococcus viridans, einMicrococcus sp.). Die Verträglichkeit der Behandlung war gut. Schwere Nebenwirkungen traten nicht auf. Die gemessenen Konzentrationen von Ofloxacin in Serum und Speichel waren vergleichbar zwischen Patienten und gesunden Kontrollen. Sie waren im Speichel höher als im Serum. Ofloxacin sollte zur Prophylaxe bakterieller Infektionen bei Granulozytopenie als eine mögliche geeignete Alternative zu Trimethoprim-Sulfamethoxazol weiter untersucht werden. Das Risiko einer Koloniserung durch Ofloxacin-resistente Pseudomonaden muß dabei beachtet werden.

     

Efficiency and safety of optically modified fiber tips for laser angioplasty

To evaluate the safety and efficiency of optically modified fiber tips, craters were created in human cadaver atherosclerotic arterial walls using sapphire contact probes and lensed fibers connected to a continuous wave neodymium yttrium aluminum garnet (Nd-YAG) laser. Laser energy was emitted at a constant level of 50 J. The sapphire contact probe catheter consisted of a round 2.2 mm diameter synthetic sapphire attached to an 8F catheter into which a 0.2 mm diameter optical fiber was inserted with the distal tip maintained at 3 mm from the sapphire. The lensed fiber catheter consisted of a 0.2 mm optical fiber at the end of which a 1 mm diameter lens was made. The fiber was inserted into a 5F low profile balloon catheter with the lens maintained 3 mm beyond the catheter tip. During laser emissions the catheter tips were maintained in a stationary position in contact with tissue targets immersed in blood at an angle of 90 degrees. The diameter of holes at the entry and exit of craters, the depth of craters and thermal injury to adjacent tissue (rim of carbonization and vacuolization) were measured with microscopy. The volume of tissue removed was derived from these values. Controlled effect index was determined as the ratio of diameter of holes and the extent of thermal injury. Efficiency was determined as the ratio of volume of tissue removed and the energy required to vaporize tissue.(ABSTRACT TRUNCATED AT 250 WORDS)     

Exhaled breath condensate acidification in acute lung injury

Lung injury in ventilated lungs may occur due to local or systemic disease and is usually caused by or accompanied by inflammatory processes. Recently, acidification of exhaled breath condensate pH (EBC-pH) has been suggested as marker of inflammation in airway disease. We investigated pH, ammonia, Lactate, pCO2, HCO3-, IL-6 and IL-8 in EBC of 35 ventilated patients (AECC-classification: ARDS: 15, ALI: 12, no lung injury: 8). EBC-pH was decreased in ventilated patients compared to volunteers (5.85 +/- 0.32 vs. 7.46 +/- 0.48; P < 0.0001). NH4+, lactate, HCO3-, pCO2, IL-6 and IL-8 were analyzed in EBC and correlated with EBC-pH. We observed correlations of EBC-pH with markers of local (EBC IL-6: r = -0.71, P < 0.0001, EBC IL-8: r = -0.68, P < 0.0001) but not of systemic inflammation (serum IL-6, serum IL-8) and with indices of severity of lung injury (Murray's Lung Injury Severity Score; r = -0.73, P < 0.0001, paO2/FiO2; r = 0.54, P < 0.001). Among factors potentially contributing to pH of EBC, EBC-lactate and EBC-NH4+ were found to correlate with EBC-pH. Inflammation-induced disturbances of regulatory mechanisms, such as glutaminase systems may result in EBC acidification. EBC-pH is suggested to represent a marker of acute lung injury caused by or accompanied by pulmonary inflammation.