Interaction of Pseudomonas aeruginosa plasmids and mu-like phages: the suppression of the early stages of cell infection by phage D3112 in the presence of plasmid RPL11

The growth of Mu-like, D3112, B39 and B3 bacteriophages of Pseudomonas aeruginosa on bacterial strains containing R plasmids was studied. Plasmids RPL11, Rms148 and Rms163 were shown to interfere with phage growth: 1) D3112 and B39 phages do not produce plaques on a lawn of PAO1 (Rms148) giving e.o.p. less than 10(-9); 2) RPL11 plasmid restricts phage D3112 growth (e.o.p. less than 10(-9), the growth of phage B3 being also restricted by this plasmid, though in considerably less extent; 3) phage B39 makes small and very turbid plaques on a lawn of PAO1 (Rms163) with e.o.p. 0,13, while c mutants form clear plaques on this lawn and grow with e.o.p. 1,0. The interference of plasmid RPL11 with phage D3112 growth was examined in detail. The plasmid did not affect phage D3112 adsorption and no restriction of phage DNA in R+ cells was found. However, phage genes controlling establishment of lysogeny and the lytic cycle were not expressed after infection. It was observed though, that if a cell contains both prophage D3112 and plasmid RPL11, no interference with repressor synthesis or phage development takes place after induction of prophage. The results obtained allow to conclude that: 1) RPL11 plasmid interference with phage D3112 growth is caused by the plasmid effect on one of the early stages in the development preceding phage DNA integration; 2) the process of primary integration after infection and that of reintegration of DNA after prophage induction are likely to differ.     

Protein metabolism in burned rats

Incorporation of [2-14C]glycine was used to estimate serum protein synthesis in four groups of rats. These were the control (group C); 20% body surface burn (group B); 20% burn, seeded with Pseudomonas aeruginosa (group BI); and burned-infected treated topically with mafenide (alpha-amino-p-toluenesulfonamide) acetate (group BIS), a treatment which controls P, aeruginosa burn-wound infection in humans. On the 6th day postburn the relative specific activities of all fractions were increased in the order BI greater than BIS greater than B greater than C, as were the concentrations of the globulins; Serum albumin concentration fell, being lowest in BI. Tissue albumin contents, measured by radioimmunoassay, of eviscerated blood-free bodies of rats were (mg/100 g rat wt): C, 207; B, 294; BI, 256. Analyses of individual tissues showed that the difference was due to increased albumin content in the burn-wound area. The tissue albumin was of normal molecular size and was immunologically reactive. We conclude that the prolonged hypoalbuminemia following burn injury is not a consequence of impaired albumin synthesis, but a result of altered compartmentation.     

Fatal systemic mycotic infections in the burned child

Two cases of systemic phycomycotic burn wound infection occurred in severely burned children. Both patients, although treated aggressively, died after systemic colonization through the burn wound by fungi. Modern burn therapy has increased survival of many severely burned children but opportunistic fungal infection remains as an ominous threat. Early recognition, wide excision or amputation, and systemic antifungal agents comprise the current clinical armamentarium against systemic fungal invasion of burn wounds.     

Reduced dose of subcutaneous cladribine induces identical response rates but decreased toxicity in pretreated chronic lymphocytic leukaemia. Swiss Group for Clinical Cancer Research (SAKK)

We report a case of ulcer bed infection in an enlarging venous leg ulcer without clinical signs of cellulitis in the surrounding tissues. Signs of infection in the leg ulcer were: 1) cocci-like structures and bacteria-like rods around vessel walls in the viable ulcer bed, 2) vasculitis-like inflammation of deeply situated vessels of the viable tissue, 3) Pseudomonas aeruginosa-specific antibodies in the serum (other than against exotoxin A), 4) extensive epidermolysis of normal human skin by the wound exudate in vitro, and 5) P. aeruginosa exotoxin A in the wound exudate (23 ng/ml). In an in vitro cell assay, the wound exudate was cytotoxic and rabbit antibodies to exotoxin A, but not a serine proteinase inhibitor, inhibited this cytotoxicity. P. aeruginosa exotoxin A might contribute to the pathogenesis of the ulcer enlargement. The ulcer improved after the third skin graft, probably mainly due to effective treatment with a long-stretch compression bandage.     

Role of alveolar macrophages in initiation and regulation of inflammation in Pseudomonas aeruginosa pneumonia

To evaluate the role of alveolar macrophages (AMs) in acute Pseudomonas aeruginosa pneumonia in mice, AMs were depleted by aerosol inhalation of liposomes containing clodronate disodium. AM-depleted mice were then intratracheally infected with 5 x 10(5) CFU of P. aeruginosa. In addition to monitoring neutrophil recruitment and chemokine releases, lung injury was evaluated soon after infection (8 h) and at a later time (48 h). At 8 h, depletion of AMs reduced neutrophil recruitment, chemokine release, and lung injury. At 48 h, however, depletion of AMs decreased bacterial clearance and resulted in delayed movement of neutrophils from the site of inflammation with aggravated lung injury. With instillation of 5 x 10(7) CFU of bacteria, AM-depleted mice showed low mortality within 24 h of infection but high mortality at a later time, in contrast to non-AM-depleted mice. These results demonstrate that depletion of AMs has beneficial early effects but deleterious late effects on lung injury and survival in cases of P. aeruginosa pneumonia.     

The 1995 Moyer Award. The effect of burn injury on allograft rejection, alloantigen processing, and cytotoxic T-lymphocyte sensitization

Burn injury impairs cellular immunity, increases the risk of viral infection, and delays allograft rejection, but little is known about its effect on antigen processing and cytotoxic T-lymphocyte (CTL) function. This study examined the effect of burn injury on alloantigen sensitization with an in vivo model of second-set rejection and in vitro assays of CTL alloreactivity. Anesthetized CBA mice (n = 95) received a 0%, 20%, or 40% full-thickness contact burn that was partially excised 3 days later and covered with autograft or C57BL/6 allograft. Two weeks after the burn was inflicted, mice were challenged with second-set tail allografts, which were observed for rejection. Median graft survival times were compared by Wilcoxon rank and chi-squared analysis. Additional CBA mice (n = 24) underwent similar burn injury, excision, and grafting. Splenocytes were harvested 2 weeks later and were used as CTL effectors against radiolabeled targets. Dilution curves of target lysis were compared by analysis of variance. Forty percent burn injury prolonged unprimed allograft survival from 13 to 15 days (p < 0.01) but had a greater effect on primed allograft survival, which increased from 9 to 12.5 days (p < 0.01). Furthermore, a 40% burn eliminated the influence of priming, resulting in second-set graft survival similar to that of mice in an unburned, unprimed control group (12.5 vs. 13 days, NS). Whereas 20% burn injury did not inhibit CTL priming, a 40% burn profoundly impaired CTL function (p < 0.001), which recovered only after 6 days of in vitro allostimulation. Burn injury inhibits both alloantigen priming and the immunologic memory of CTLs as a function of burn size. This impairment in alloantigen processing helps to explain defects in cellular immunity and suggests a mechanism for prolonged allograft survival and decreased viral resistance after burn injury occurs.     

Individual effects on biomechanical variables during landing in tennis shoes with varying midsole density

A new silver-coating technology was developed to prevent wound adhesion, limit nosocomial infection, control bacterial growth, and facilitate burn wound care through a silver-coated dressing material. For the purposes of this article, Acticoat (Westaim Biomedical Inc, Fort Saskatchawan, Alberta, Canada) silver-coated dressing was used. After in vitro and in vivo studies, a randomized, prospective clinical study was performed to assess the efficacy and ease of use of Acticoat dressing as compared with the efficacy and ease of our institution's standard burn wound care. Thirty burn patients with symmetric wounds were randomized to be treated with either 0.5% silver nitrate solution or Acticoat silver-coated dressing. The dressing was evaluated on the basis of overall patient comfort, ease of use for the wound care provider, and level of antimicrobial effectiveness. Wound pain was rated by the patient using a visual analog scale during dressing removal, application, and 2 hours after application. Ease of use was rated by the nurse providing wound care. Antimicrobial effectiveness was evaluated by quantitative burn wound biopsies performed before and at the end of treatment. Patients found dressing removal less painful with Acticoat than with silver nitrate, but they found the pain to be comparable during application and 2 hours after application. According to the nurses, there was no statistically significant difference in the ease of use. The frequency of burn wound sepsis (> 10(5) organisms per gram of tissue) was less in Acticoat-treated wounds than in those treated with silver nitrate (5 vs 16). Secondary bacteremias arising from infected burn wounds were also less frequent with Acticoat than with silver nitrate-treated wounds (1 vs 5). Acticoat dressing offers a new form of dressing for the burn wound, but it requires further investigation with greater numbers of patients in a larger number of centers and in different phases of burn wound care.     

The contribution of a bacterially isolated environment to the prevention of infection in seriously burned patients

A new system of patient protection from bacterial crossinfection called the Bacteria Controlled Nursing Unit (BCNU) is described, based on strict environmental control of a 6 x 10 foot area surrounding the patient's bed rather than the entire patient room or isolation ward, plus the ability to deliver all medical care without entering the protective environment and maintaining all monitoring, life support, and i.v. equipment outside the controlled environment. The clinical effectiveness of this system in the treatment of burn patients has been studied and compared with the effectiveness of single room isolation on a burn isolation ward and conventional isolation techniques on an open burn ward. The studies show that the BCNU is significantly more effective in preventing bacterial cross-contamination than conventional precautions (3.8% vs. 13.1%, P < 0.001; and 8% vs. 22.8%, P < 0.001) over a two and four week period. The studies also indicate that there was a significant increase in the probability of infection occurring following cross-contamination than occurring after auto-contamination (65% vs. 39%, P < 0.005), emphasizing the importance of preventing cross-contamination in reducing the overall infection rate in seriously burned patients. Clinical evaluation of the unit proved it to be compatible with intensive nursing and medical care without increasing the nurse to patient ratio. The unit provided sufficient control of bacterial cross-infection to allow reduction in mortality and improvement in the effectiveness of burn care through routine prompt excision of burn eschar and immediate wound closure to be carried out in severe and massively burned patients without a limiting threat of bacterial burn wound sepsis.     

Prolongation of allograft survival by 1,25-dihydroxyvitamin D3

BACKGROUND: 1,25-Dihydroxyvitamin D3, the hormonal form of vitamin D, is now believed to play a significant role in the immune responses, both in vitro and in vivo, preventing the development of several autoimmune diseases. These studies suggest that 1,25-dihydroxyvitamin D3 may be effective in prolonging allograph survival. METHODS: To test the hypothesis that 1,25-dihydroxyvitamin D3 would prolong allograft survival, neonatal heart grafts were transplanted to allogeneic recipients receiving either 19-nor-1,25-dihydroxyvitamin D2 (200 ng/day) or 1,25-dihydroxyvitamin D3 (50 ng/mouse/day) orally through the diet. The efficacy of 1,25-dihydroxyvitamin D3 in prolonging graft survival in a vascularized model was determined by heterotopic ACI to Lewis heart transplants. RESULTS: The provision of exogenous 1,25-dihydroxyvitamin D3 or an analog, 19-nor-1,25-dihydroxyvitamin D2, to mice markedly prolonged the survival of neonatal mouse heart allografts. Similar results were obtained with a vascularized heterotopic heart transplant model in rats. Cyclosporine at a maximum 25 mg/kg dose for mice proved less effective than 1,25-dihydroxyvitamin D3. Graft survival in mice differing at class I and class II loci (B10.A(4R) --> C57BL/10) increased from 13.0+/-1.1 days to 51.0+/-5.6 days and was significantly better than cyclosporine monotherapy (33.2+/-3.6). Rat heart survival in a high responder strain combination (ACI --> Lewis) increased from 6.2+/-0.3 to 25.2+/-2.8 days. The increased survival of the transplants brought about with 1,25-dihydroxyvitamin D3 was not accompanied by hypercalcemia in rats. CONCLUSION: These results suggest that 1,25-dihydroxyvitamin D3 can be used as an effective agent in preventing graft rejection.     

Effect of 1,3-dithia-2-thioxo-cyclopent-4-ene and its derivatives on liver injury induced by carbon tetrachloride and orotic acid in rats

The protective effect of 1,3-dithia-2-thioxo-cyclopent-4-ene (DT827A) and its two derivatives of 4-phenyl-1,3-dithia-2-thioxo-cyclopent-4-ene (DT827B) and 4-(4-fluorophenyl)-1,3-dithia-2-thioxo-cyclopent-4-ene (DT827C) on liver injury induced by carbon tetrachloride (CCl4) and orotic acid was studied using male rats. The approximate lethal doses were about 100 mg/kg for DT827A-treated animals and more than 800 mg/kg for the other two compounds-treated groups. Single oral administration of the three test compounds at the dose levels of 2 and 10 mg/kg 1 hour before CCl4 exposure revealed a protective effect on the findings of centrolobular necrosis, balloon cells and macrophage infiltration in histopathological findings in livers in the order of DT827B-treated rats > DT827A-treated rats > DT827C-treated rats. Repeated oral administration of the compounds at the dose levels of 2 and 10 mg/kg/day for 10 consecutive days revealed a protective effect against liver injury on the findings of centrolobular necrosis, balloon cells and macrophage infiltration in the order of DT827B-treated rats > DT827A-treated rats [symbol: see text] DT827C-treated rats. Simultaneous administration of the compounds at the dose level of 10 mg/kg/day together with a high sucrose diet containing orotic acid for 12 days revealed an inhibitory effect on fatty liver formation in the order of DT827B-treated rats > DT827C-treated rats > DT827A-treated rats. A hepatoprotective potential of the DT827 series compounds was suggested under the conditions of these studies, and DT827B was considered to be the most effective.     

Identification of the dopamine D3 receptor in oligodendrocyte precursors: potential role in regulating differentiation and myelin formation

Expression of the dopamine D3 receptor (D3r) was found in primary mixed glial cultures from newborn brain and in the corpus callosum in vivo during the peak of myelination. Expression of the D3r mRNA, but not D2r mRNA, was detected as early as 5 d in vitro (DIV) by RT-PCR. Immunoblot studies revealed D3r protein was also expressed in the cultures. Double immunofluorescence analysis for the D3r and for surface markers of specific stages of oligodendrocyte development indicated that D3r expression occurred in precursors and in immature oligodendrocytes but not in mature oligodendrocytes (i.e. , A2B5(+) 007(-) 01(-) and A2B5(+) 007(+) 01(-) cells but not A2B5(-) 007(+) 01(+) cells). Confocal microscopic analysis indicated that D3r was associated with cell bodies and cell membranes but not with the processes emanating from cell somas. Immunohistochemistry of brain sections revealed the presence of D3r in some oligodendrocytes located mainly within the genu and radiato of the corpus callosum during the active period of myelination. Treatment of cultures with 20 microM quinpirole led to decreased numbers of O1(+) oligodendrocytes possessing myelin-like membranes as well as an increase in the number of precursors in 14 DIV cultures. This effect was prevented by the dopamine antagonist haloperidol. These results show that the D3r expression is not restricted to neurons but it is also expressed in differentiating oligodendrocytes before terminal maturation. It also suggests that dopamine or some other D3r ligand may play a role in oligodendrocyte differentiation and/or the formation of myelin by mature oligodendrocytes.     

Induction and enhancement of normal human megakaryocyte polyploidization are concomitant with perturbation in the actin metabolism

BACKGROUND: Megakaryocyte polyploidization results from the lack of cytoplasmic separation while the nucleus keeps dividing. METHODS: To investigate the role of actin in the megakaryocyte polyploidization, three human cell lines with megakaryocytic properties (DAMI, HEL and K562) were incubated in the presence of cytochalasin B, an inhibitor of actin polymerization. These data were then compared with normal megakaryocytes. RESULTS: Compared with control conditions, cells cultured in the presence of cytochalasin B revealed an augmentation of cell size and ploidy and an arrest of cell proliferation. The expression of platelet membrane glycoproteins Ib, IIb/IIIa, IIIa and thrombospondin and transferrin receptors was augmented after treatment with cytochalasin B. Physiologically, the role of actin in inducing polyploidization could be related to an imbalance between G- and F-actins. To test this hypothesis, we measured G-, F- and total actin in cytochalasin B-treated cells. Actin was found to be increased significantly in cytochalasin B-treated DAMI and HEL cell lines. In contrast, the G/F-actin ratio was not affected by cytochalasin B. To confirm these actin changes in physiological megakaryocytopoiesis, G- and F-actin contents were then estimated in normal megakaryocytes. The G- and F-actin contents of megakaryocytes from eight normal patients exponentially decreased from 2 to 128n, whereas the total actin content per cell kept increasing. The G/F ratio was unaffected. CONCLUSION: Polyploidization of human megakaryocytes results from either a diminution of actin synthesis or an increased actin turnover, which in turn possibly abrogates the formation of the actin cleavage furrow in telophasis.     

Expression of cyclins A, D2 and D3 in individual normal mitogen stimulated lymphocytes and in MOLT-4 leukemic cells analyzed by multiparameter flow cytometry

Cyclins are regulatory subunits of the cyclin dependent kinases (CDKs), the enzymes that drive the cell through the respective phases and check-points of the cell cycle. The expression of cyclins in non-tumor cells, regulated by timely induction of their synthesis and proteolysis, is scheduled, occurring at discrete periods of the cell cycle. Using multiparameter flow cytometry we have recently observed that expression of cyclins B1 and E in individual normal lymphocytes mitogenically stimulated by phytohemagglutinin (PHA) and lymphocytic leukemic MOLT-4 cells was similar, restricted to particular phases of the cycle: cyclin B1 was detected only in G2+M- and cyclin E in late G1 and early S-phase cells. In the present study we have measured the expression of cyclins A, D2 and D3 in these cells. The presence of cyclin A was restricted to late S and G2 phases, both in the case of lymphocytes and of MOLT-4 cells. Over 95% of the non-stimulated lymphocytes were both cyclin D2 and D3 negative. Mitogenic stimulation with PHA-induced expression of cyclins D2 and D3 in over 50% cells, which corresponds to the percentage of cells that respond to this mitogen in cultures. Expression of these proteins peaked between 8 and 24 h after addition of PHA, and then decreased at the time of cell entrance to S. During exponential growth (48-72 h after stimulation with PHA) expression of the D-type cyclins was diminished: only between 5-10% of the lymphocytes had levels of cyclin D3 as high as G1 cells between 8-24 h after PHA stimulation. Populations of proliferating lymphocytes and MOLT-4 cells were very heterogeneous in terms of expression of D-type cyclins by individual cells. While expression of cyclin D2 in exponentially growing MOLT-4 cells was similar to that of proliferating lymphocytes, the percent of cells expressing cyclin D3 as well as the degree of expression, was higher in MOLT-4 cells, regardless of the phase of the cycle. These results, with our earlier observations of the untimely expression of cyclins B1 and E in several other tumor lines, suggest that altered expression of cyclins may be a frequent feature of malignancy.     

IL-10 improves lung injury and survival in Pseudomonas aeruginosa pneumonia

Pseudomonas aeruginosa is the most frequent Gram-negative pathogen causing nosocomial pneumonia. Four different strains of P. aeruginosa (including three isogenic transposon mutants) were utilized in experiments in mice to characterize the specific patterns of cytokine generation in response to bacterial products and cytotoxicity. Intratracheal instillation of any of the strains led to the up-regulation of IL-1beta, IL-6, and TNF-alpha mRNA. Instillation of the cytotoxic strains (PA103, PA103tox::omega) led to IL-10 mRNA up-regulation in the lungs and increased concentrations of IL-10 in the blood. In contrast, the instillation of the noncytotoxic strains (PA01, PA103exsA::omega) did not lead to an increase in IL-10 mRNA in the lungs or to an increase of IL-10 concentration in blood. IL-10 production appears to be a response to either cellular injury or to specific cytotoxic exoproducts produced by the bacteria. The systemic administration of rIL-10 significantly decreased the lung injury and the mortality in mice who had received the cytotoxic strains. The improvement in survival induced by administration of rIL-10 required the concomitant presence of IFN-gamma, as blockade of IFN-gamma with a neutralizing Ab led to 100% mortality, despite the administration of rIL-10. These results suggest that IL-10 is produced in response to specific bacterial products and that there is a potential role for IL-10 in the treatment of cytotoxic P. aeruginosa pneumonia.     

Our experience with the use of cerium sulphadiazine in the treatment of extensive burns

The development of the burn disease with infection as the most important complication represents still a major problem in burn patients. With the introduction of the method of early surgical excision of the Af1p4r with immediate grafting in major burns, improved survival has been achieved, particularly in children. However, especially in adults, early massive excisions did not prove to be of much benefit for survival. In these cases, more-or-less sequential staged excisional procedures have been introduced by many renown burn surgeons. In 1976 Monafo et al. presented the cerium nitrate-silver sulphadiazine cream (CSD) combination for topical therapy. The addition of 2.2% of the rare earth metal cerium salt to silversulphadiazine causes the formation of a relatively hard, yellow, leather-like eschar with excellent resistance to infection and good long-term adherence to the burn wound. This allows the surgeon to perform late tangential excision and immediate autografting thus decreasing the open wound size and the rate of severe infections originating in the burn wound itself. We report our experience with the treatment of 20 patients with deep burns exceeding 20% of the BSA with cerium nitrate-silver sulphadiazine cream compared with a similar group of burn patients treated by silver sulphadiazine cream alone. CSD proved to be safe and effective in the treatment of deep and extensive burns. Its advantages include easy and painless application and removal, turning the necrotic skin to yellow, and a leathery crust with good resistance to infection, thus enabling later, or staged, sequential excisions in cases where early massive excisions are not possible.     

Mixed tumors of the pineal area. Diagnosis and therapy consisting of secreting germ cell tumor

This study examined the effects of early burn wound excision on gastric blood flow and on morphologic changes in mucosal vessels. Wistar rats were given a 30% total body surface area burn and divided into four groups, consisting of control animals (group 1), animals with burn injury without and with fluid resuscitation (groups 2 and 3, respectively), and animals with both fluid resuscitation and early wound excision (group 4). Gastric mucosal blood flow (GMBF) was measured by the hydrogen gas clearance method up to 24 h post-burn. Morphologic changes in mucosal vessels were examined by scanning electron microscopy (SEM) at 3 and 24 h post-burn. The GMBF sharply decreased in the acute period after the burn. In group 4, however, it recovered to the initial value by 6 h post-burn and there was no significant change throughout the experiment. Morphologically, although the mucosal capillaries revealed some changes such as irregularity in diameter in groups 2-4 at 3 h, most of mucosal capillaries retained their original appearance in group 4 at 24 h post-burn. These result suggest that early excision does not aggravate the state of gastric ischemia.     

Low calcium diet and 1,25-dihydroxyvitamin D(3) infusion modulate immune responses during Mycobacterium paratuberculosis infection in beige mice

A 12-month study was conducted to evaluate the effects of feeding a low calcium (Ca) diet or 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3) infusion on the persistence of Mycobacterium paratuberculosis infection using a mouse model. Male beige mice 6-8 weeks of age were assigned to one of the following treatments: (1) non-infected, (2) infected,(3) non-infected/1,25(OH)(2)D(3), (4) infected/1,25(OH)(2)D(3), and (5) infected/low Ca (0.15 percent) diet. Infected mice were inoculated intravenously with live M. paratuberculosis. At 1, 6 and 12 months postinfection, mice in Treatments 3 and 4 were implanted subcutaneously with mini-osmotic pumps to deliver 1,25(OH)(2)D(3). Infusion with 1,25(OH)(2)D(3) exacerbated M. paratuberculosis infection in most tissues at all time points. Mice infused with 1,25(OH)(2)D(3) had higher bacterial counts in spleen, liver, and ileum compared with control infected mice after 1 month of infection. In contrast, feeding a low Ca diet reduced the number of viable organisms cultured from the liver and ileum of infected mice. Plasma Ca and 1,25(OH)(2)D(3) were increased in mice infused with 1,25(OH)(2)D(3) at all time points but values for low Ca mice were not different than for non-infused mice. Splenocyte production of TNF, IL-1 and IL-6 was higher for mice fed the low Ca diet compared with control infected mice after 1 month of infection. Inducible IL-6 activity remained higher for this treatment at 6 months postinfection. These results suggest that feeding a low Ca diet to mice chronically infected with M. paratuberculosis appears to enhance their ability to clear the infection in a manner distinct from any effect of 1,25(OH)2D3.     

Class restriction of cephalosporin use to control total cephalosporin resistance in nosocomial Klebsiella

CONTEXT: Resistance to most or all cephalosporin antibiotics in Klebsiella species has developed in many European and North American hospitals during the past 2 decades. OBJECTIVE: To determine if restriction of use of the cephalosporin class of antibiotics would reduce the incidence of patient infection or colonization by cephalosporin-resistant Klebsiella. DESIGN: A before-after comparative 2-year trial. SETTING: A 500-bed, university-affiliated community hospital in Queens, NY. PATIENTS: All adult medical and surgical hospital inpatients. INTERVENTION: A new antibiotic guideline excluded the use of cephalosporins except for pediatric infection, single-dose surgical prophylaxis, acute bacterial meningitis, spontaneous bacterial peritonitis, and outpatient gonococcal infection. All other cephalosporin use required prior approval by the infectious disease section. MAIN OUTCOME MEASURE: Incidence of patient infection or colonization by ceftazidime-resistant Klebsiella during 1995 (control period) compared with 1996 (intervention period). RESULTS: An 80.1% reduction in hospital-wide cephalosporin use occurred in 1996 compared with 1995. This was accompanied by a 44.0% reduction in the incidence of ceftazidime-resistant Klebsiella infection and colonization throughout the medical center (P<.01), a 70.9% reduction within all intensive care units (P<.001), and an 87.5% reduction within the surgical intensive care unit (P<.001). A concomitant 68.7% increase in the incidence of imipenem-resistant Pseudomonas aeruginosa occurred throughout the medical center (P<.01). All such isolates except one were susceptible to other antibiotics. CONCLUSION: Extensive cephalosporin class restriction significantly reduced nosocomial, plasmid-mediated, cephalosporin-resistant Klebsiella infection and colonization. This occurred at the price of increased imipenem resistance in P aeruginosa, which remained susceptible to other agents. Thus, an overall reduction in multiply-resistant pathogens was achieved within 1 year.     

Effect of vitamin D3 and 1,25(OH)2D3 on growth of neoplastically derived cell lines and their alkaline phosphatase activity

Inhibitory effects of 1,25(OH)2D3 and D3 on growth of four neoplastically derived cells were observed in human acute leukemia cell culture CEM-C-1 and CEM-C-7, human cervical carcinoma cell lines C-4-1 and human epithelioid carcinoma cells of cervix HeLa S3K. Concurrently, in dexamethasone-responsive cells C-4-1 and HeLa S3K there was a 1,25(OH)2D3 and D3 induced elevation of alkaline phosphatase with 1,25(OH)2D3 showing the greater effects. It is supposed that vitamins D3-induced alkaline phosphatase activity in malignant cells, which is proposed to be a possible marker of cell differentiation, can be associated with the membrane effects of these vitamins.