Polymorphonuclear leukocyte functions and multiple sclerosis.

We tested peripheral blood from 60 patients with definite multiple sclerosis (MS) and 60 healthy controls for polymorphonuclear leukocyte (PMNL) functions and found significant disorders in adherence (9.07% +/- 8.18% for patients versus 28.97% +/- 5.76% for controls), chemotaxis (18.32 +/- 3.1 for patients versus 30.49 +/- 4.52 for controls), phagocytosis (73.6 +/- 25.25 for patients versus 111.2 +/- 25.7 for controls), and bactericidal action (10.35% +/- 5% for patients versus 25.09% +/- 4.82% for controls). All differences were significant (p < 0.001). We confirmed the results by retesting 3 to 8 months later. The depressed PMNL functions in MS patients may explain their increased susceptibility to infections of the respiratory, digestive, and urinary tracts.

Adherence of Candida albicans to epithelial cells from normal and cancerous urinary bladders.

Patients with malignancies are at high risk to develop infections by Candida albicans. We have compared the adherence of C. albicans isolated from urine cultures to bladder epithelial cells obtained from healthy volunteers and patients with cancer of the bladder. The mean number of C. albicans adhering per epithelial cell from areas infiltrated from cancer was significantly higher as compared to cells obtained from intact areas of cancerous bladders and from normal bladders. The increased adherence of C. albicans to cancerous epithelial cells suggests that malignancies are associated with alterations of the epithelial cell surface which render the cells more susceptible to colonization by C. albicans. The increased colonization may predispose these patients to C. albicans infections.

In vivo potentiation of polymorphonuclear leukocyte function by ciprofloxacin.

Ciprofloxacin was administered to 10 healthy volunteers at a dose of 250 mg orally. Serum and polymorphonuclear leukocytes (PMNLs) were obtained from all subjects before the administration of the drug and 12 hours after the administration. In addition serum was obtained from all subjects at 24 and 48 hours after ciprofloxacin administration. All sera and PMNLs were used for the chemotactic, phagocytic and killing determinations of the PMNLs. The results demonstrated that serum obtained 12 hours after the administration of ciprofloxacin potentiates PMNL chemotactic activity (chemotactic index (CI) = 33.0 +/- 4.2 microns (means +/- S.D.)) as compared to the chemotactic activity generated by serum obtained prior to administration of the drug, CI = 20.4 +/- 4.4 microns (p < 0.01). Serum obtained 24 and 48 hours after ciprofloxacin administration did not stimulate PMNL function. The administration of ciprofloxacin did not have any direct influence on the PMNLs in terms of their chemotactic response. Furthermore, serum obtained after the administration of ciprofloxacin markedly enhanced PMNL phagocytosis and killing of all organisms tested. Ciprofloxacin also acted directly on the PMNLs and increased their bactericidal activity. These results demonstrate that ciprofloxacin potentiates PMNL function in vivo which may be of potential clinical benefit.

Trimethoprim, sulphamethoxazole, bacterial adhesion and polymorphonuclear leucocyte function.

Culturing Escherichia coli, Proteus mirabilis and Klebsiella pneumoniae in the presence of subinhibitory concentrations (1/4 MIC) of trimethoprim, sulphamethoxazole or their combination, resulted in reduced adherence of all the above strains. The number of phagocytosed bacteria pre-exposed to subinhibitory concentrations of the above antibiotics was not significantly changed, but a significant increase of bactericidal activity of the polymorphonuclear leucocytes was observed. Furthermore, filtrates of K. pneumoniae and P. mirabilis grown in the presence of trimethoprim alone or in combination with sulphamethoxazole induced an increased chemotactic response of human polymorphonuclear leucocytes.

Survival of bacteriophage 1 of the Salmonella typhimurium phage typing scheme in different liquid pharmaceutical preparations.

The survival of bacteriophage 1 of the Salmonella typhimurium phage typing scheme was studied in seven commonly used liquid pharmaceutical preparations of different composition. Commercially available flacons of Septobore colyre, Thilodexine eye drops, Bradoral gargle solution, Novalgin drops, Garamycin injection, Anatoxal-antigen tetanic purificate and Antidiphtheric serum, were used. It was found that the phage viability in these drugs varied greatly. Thus in Septobore the page was almost completely eliminated in less than one week, while in Garamycin the number of plaque forming units (PFU) remained stable during the experiment (18 months). The viability of the phage showed intermediate values in the other five pharmaceutical preparations. The possible reasons for these differences in viability and the significance of phage (and viruses) survival in medicins are discussed.

In-vivo effects of clindamycin on polymorphonuclear leucocyte phagocytosis and killing of gram-negative organisms.

Polymorphonuclear leucocyte (PMNL) phagocytosis and killing were evaluated in ten healthy volunteers who had received 600 mg of clindamycin intramuscularly. Serum obtained 3 h after the administration of clindamycin significantly increased PMNL phagocytosis and killing of Gram-negative aerobic organisms. Serum obtained at 12 and 24 h after the administration of the drug did not induce a significant increase in PMNL phagocytosis and killing. The administration of clindamycin had no direct effect on the PMNLs in terms of their phagocytic and bactericidal function. These results demonstrate serum-associated augmentation of PMNL function by clindamycin in vivo which may be of potential clinical benefit in the outcome of infections.

Transient improvement of polymorphonuclear leukocyte function by splenectomy in beta-thalassemia.

Host defense mechanisms in transfusion-dependent non-splenectomized patients with beta-thalassemia were studied. Polymorphonuclear leukocytes (PMNLs) of non-splenectomized patients responded poorly to zymosan generated chemotactic factors. Chemotactic indices were 22.1 microns +/- 2.8 (mean +/- S.D.) using zymosan activated serum (ZAS) as the attractant in comparison to 20.4 microns +/- 2.6 when fresh untreated serum was used. In contrast, chemotactic indices of normal PMNLs increased from 21.1 microns to 33.6 microns +/- 3.1 in response to ZAS. Normal PMNL responses to a mixture of normal ZAS and thalassemic serum were inhibited; the mean chemotactic index was 18.1 microns +/- 5.1 with use of ZAS alone. Splenectomy temporarily reverses these alterations. Adherence to nylon wool of PMNLs suspended in fresh thalassemic serum prior to splenectomy was 3.1% +/- 1.1 (mean +/- S.D.); 20 days after splenectomy adherence increased to 14.0% +/- 2.8 (P = 0.0001) and remained at this level for 90 days. At 120 and 150 days after splenectomy adherence decreased to 1.5% +/- 0.8 and 1.0% +/- 0.85 respectively. Splenectomy also transiently abrogated the failure of zymosan to generate chemotactic factors in thalassemic serum.

Effects of methylprednisolone and dexamethasone on polymorphonuclear leukocyte adherence in vivo.

It has been proposed that corticosteroids may be effective in the treatment of shock and the adult respiratory distress syndrome (ARDS) by inhibiting complement-induced granulocyte aggregation and by disaggregating granulocyte aggregates in vitro. In the present investigation we have examined the effects of sera from patients who had received comparable doses of methylprednisolone (MP) and dexamethasone (DEX) on the adherence of polymorphonuclear leukocytes (PMNs). Sera obtained from patients that had received MP markedly reduced PMN adherence with maximum effect noted by 8 h. In contrast, sera from patients receiving DEX had no effect on PMN adherence. The results of this study indicate that MP may be more effective in the treatment of septic shock and other conditions associated with microvascular leukostasis.

Interaction of subminimal inhibitory concentrations of clindamycin and gram-negative aerobic organisms: effects on adhesion and polymorphonuclear leukocyte function.

The effect of pre-incubation of Pseudomonas aeruginosa, Klebsiella pneumoniae and Proteus mirabilis with sub-inhibitory concentrations (sub MICs) of clindamycin on the adherence of these organisms was studied. Culturing these organisms in the presence of clindamycin (4 mg/l) resulted in significant enhancement of adherence for Ps. aeruginosa and Pr. mirabilis and decreased adherence for K. pneumoniae. Furthermore, the effect of pre-exposure to clindamycin on polymorphonuclear leukocyte (PMNLs) function against these organisms was determined. Filtrates of Pr. mirabilis pre-exposed to clindamycin promoted PMNL chemotaxis. No effect on chemotaxis was noted with the filtrates of clindamycin treated Ps. aeruginosa and K. pneumoniae. PMNL phagocytosis for all the organisms was increased after they were pre-exposed to clindamycin.

Effects of subinhibitory concentrations of cefotaxime on adhesion and polymorphonuclear leukocyte function with gram-negative bacteria.

The effect of pre-incubation of Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis and Klebsiella pneumoniae with subinhibitory concentrations of cefotaxime on adherence and polymorphonuclear leukocyte function against these organisms was studied. Culturing the above organisms in the presence of cefotaxime (1/4 MIC) resulted in reduced adherence of Pseudomonas aeruginosa and Proteus mirabilis. Furthermore pre-incubation of all organisms with sub MICs of cefotaxime resulted in significant enhancement of polymorphonuclear leukocyte chemotaxis, phagocytosis and bactericidal activity against these organisms.

Interaction of subminimal inhibitory concentrations of clindamycin and Escherichia coli: effects on adhesion and polymorphonuclear leukocyte function.

Subinhibitory concentrations (sub-MICs) of clindamycin interfere with the adhesion of Escherichia coli to buccal epithelial cells and promote phagocytosis and killing of this organism by human polymorphonuclear leukocytes (PMNLs). Adherence of E. coli grown in the presence of clindamycin, at concentrations of 2-32 mg/l, varied from 21.1 +/- 7.4 to 25.8 +/- 7.8 bacteria per epithelial cell (EC) (mean +/- S.D.) as compared with 58.3 +/- 10.3 per EC when the organism was cultured in the absence of the antibiotic (P less than 0.01). The number of phagocytosed bacteria per 200 PMNLs increased from 166.1 +/- 36.6 when E. coli was grown in medium 199 containing no antibiotic, to 289.3 +/- 56.4 (P less than 0.01) when the organism was preincubated with 4 mg/l of clindamycin. The same concentration of clindamycin also increased the percentage of phagocytosed bacteria killed by the PMNLs from 42.0 +/- 9.0% to 63.7 +/- 11.2% (P less than 0.01). The results of this study indicate that sub-MICs of clindamycin enhance host-defence mechanisms against E. coli.

Interaction between Clostridium difficile and polymorphonuclear leucocytes from the elderly and post-operative cancer patients: phagocytosis and bactericidal function.

The ability of polymorphonuclear leucocytes (PMNs) from elderly healthy subjects and post-operative cancer patients to ingest and kill Clostridium difficile was studied. The percentage of phagocytosis in clinically healthy subjects aged 69-82 years ranged from 20.2 +/- 3.2 (mean +/- SD) to 34.1 +/- 4.2, depending on the strain of C. difficile, from 6.7 +/- 2.2 to 11.2 +/- 2.2 in post-operative cancer patients aged 65-69, and from 68.4 +/- 3.1 to 81.1 +/- 6.3 in young healthy control subjects. In both study groups, the defect was in part serum-associated. Although the total number of bacteria killed by the PMNs was reduced in the two study groups, the percentage of ingested bacteria killed by the PMNs was similar to that in the young healthy subjects. These differences were not noted when Escherichia coli and Staphylococcus aureus were used as the test organisms. The defective PMN function against C. difficile in the elderly and post-operative cancer patients described in this study may offer an explanation as to why these individuals are at high risk of developing antibiotic-associated colitis.

Phagocytosis and antimicrobicidal activity of polymorphonuclear leucocytes against gentamicin-sensitive and resistant strains of Pseudomonas aeruginosa.

The ability of human polymorphonuclear leucocytes (PMNs) to ingest and kill gentamicin-sensitive and resistant Pseudomonas aeruginosa strains was studied. Strains becoming resistant to gentamicin either by laboratory training or through an R-factor were more susceptible to the phagocytic and bactericidal function of the PMNs. These results may explain previous clinical and laboratory observations indicating that gentamicin-resistant strains are less virulent.

Acute pyelonephritis caused by Staphylococcus xylosus.

Staphylococcus xylosus was recovered from the urine of a patient with pyelonephritis. Antibodies against the teichoic acid of the microorganism were demonstrated in the patient's serum by the agar gel diffusion technique.

Defective adherence of polymorphonuclear leukocytes to nylon induced by thalassemic serum.

The effects of sera obtained from 18 patients with homozygous beta-thalassemia on the adherence and chemotaxis of normal polymorphonuclear leukocytes (PMNLs) was studied. The adherence of PMNLs suspended in thalassemic serum was 3.1% +/- 2.5% (mean +/- SD) compared with 17.9% +/- 8.0% adherence in control serum (P less than 0.00001). Zymosan-treated thalassemic serum did not generate chemotactic factors, and zymosan-treated normal serum did not induce chemotaxis of PMNLs suspended in thalassemic serum. When added to zymosan-treated normal plasma, thalassemic serum inhibited augmentation of PMNL adherence to nylon columns. These abnormalities were due to a heat-labile factor(s) in the sera of patients with thalassemia. Suspending PMNLs in heated thalassemic serum (56 C for 30 min) resulted in an increase of adherence to 14.6% +/- 6.2% (P less than 0.0001). PMNLs suspended in heated thalassemic serum responded normally to chemotactic attractants.

Survival of bacteriophage 1 of the Salmonella typhimurium phage typing scheme in different liquid maintenance media and at different temperatures.

The survival of Bacteriophage 1, of the Salmonella typhimurium phage typing scheme, was studied in nutrient broth, saline and distilled water at 4 degrees C, 20 degrees C and 37 degrees C. From the results of this work it can be concluded that the survival of the phage is longer at 4 degrees C in all three maintenance media and that the survival is longer in both nutrient broth and saline than in distilled water.

Enhanced chemotaxis to gentamicin-resistant strains of Pseudomonas aeruginosa.

The chemotactic response of human polymorphonuclear leukocytes (PMNLs) to gentamicin-sensitive and gentamicin-resistant strains of Pseudomonas aeruginosa was studied. Filtrates from the resistant strains markedly enhanced the chemotactic response of human PMNLs (leukotactic index [LI] = 40.4 micron), in contrast to the filtrates from the sensitive strains, which induced less migration of PMNLs (LI = 26.8 micron). This finding may explain previous observations that suggested that gentamicin-resistant strains of P. aeruginosa are less virulent than gentamicin-sensitive strains.

Antibacterial activity of HR-756, cefoxitin and cefuroxine against multiply antibiotic-resistant strains of Enterobacteriaceae and Pseudomonas aeruginosa.

The in vitro antibacterial activity of HR-756 compared to cefoxitin and cefuroxime. 122 multiresistant clinical isolates including Enterobacteriaceae (104) and P. aeruginosa (18), which present particular problems in antibiotic chemotherapy, were selected for study. HR-756 inhibited all the stains of S. marcescens, P. mirabilis and indole-positive Proteus spp. at a concentration of 1,3 and 12 micrograms/ml, respectively; beta-lactamase-producing strains were also susceptible. 90% of K. pneumoniae and more than half of the Enterobacter and P. aeruginosa were inhibited from the drug at a concentration 16 microgram/ml. Cefoxitin and cefuroxime were less active than HR-756. Cefoxitin was more effective against S. marcescens and P. mirabilis while the same was the case with cefuroxime against K. pneumoniae strains. The greater efficiency of HR-756 over cefoxitin and cefuroxime against these multiply resistant isolates seems to be due not only to its indifference to the beta-lactamases but also to its easier penetrability into the bacterial cell.