Comparison of two antibiotic regimens in the treatment of perforated appendicitis in pediatric patients.

BACKGROUND AND PURPOSE: An increased incidence of post-surgical infectious complications in children admitted with a diagnosis of perforated appendicitis led to development of a disease-specific antibiogram and modification of our post-operative antibiotic regimen. METHODS: A historical control group comprised of 32 pediatric patients receiving ampicillin, gentamicin, and clindamycin (group AGC) was compared to a cohort of 32 children receiving ticarcillin/clavulanate plus gentamicin (group TG). The surgical procedure, peri-operative management, and inclusion, exclusion and discharge criteria were the same for each group. Outcome measures including length of stay, time to defervesce, incidence of infectious complications, and clinical failures to the antibiotic regimen were compared. RESULTS: The groups were similar with respect to gender, age, weight, surgical time, pre-operative leukocytes, and number of intra-operative bacterial isolates cultured per patient. Length of stay was 10.1 days in group TG and 12.5 days for group AGC (p = 0.0197). The number of clinical failures was reduced from 9 (28.1%) to 2 (6.3%) in group TG (p = 0.02). The time to defervesce was decreased by 1.4 days, and the number of infectious complications was reduced to 2.5-fold in group TG patients. CONCLUSIONS: Ticarcillin/clavulanate plus gentamicin was clinically more effective than ampicillin, gentamicin, and clindamycin combination therapy in the management of perforated appendicitis in our pediatric population.

Allogeneic stem cell transplantation for multiple myeloma.

High-dose chemotherapy (with or without total body irradiation) followed by allogenic marrow transplantation is curative for some patients with advanced multiple myeloma. A relatively high transplant-related mortality, however, limits the wider application of this approach. The challenge for future studies will be to develop less toxic preparative regimens, more efficient ways to prevent infection and graft-versus-host disease, and methods to enhance the graft-versus-leukemia effect of allografts.

The y1 gene of maize codes for phytoene synthase.

The cloned y1 locus of maize was sequenced and found to encode phytoene synthase. Different "wild-type" alleles of the locus were found to differ by the insertion of transposable elements in their promoter and polyA addition regions, and by the length of a CCA tandem repeat series, without any obvious effect on function of the gene. A dominant Y1 ("wild-type") allele was observed to be expressed at highest levels in the seedling but also in the embryo and endosperm. The Mu3 transposable element insertion responsible for a pastel allele of y1, which gives lowered levels of carotenoids in the endosperm of kernels and seedlings grown at high temperatures, was located in the 5' end of the gene. Although the size of the transcript from this y1 mutation suggests that the Mu3 element provides the promoter for this allele, leaf tissue in this mutant line contained approximately normal amounts of y1 mRNA. A recessive allele of y1, which conditions normal levels of carotenoids in the embryo and seedling, but almost no carotenoids in the endosperm, was found to accumulate normal amounts of y1 mRNA in the seedling and embryo, while y1 transcripts were not detected in the endosperm.

Long-term follow-up of patients with invasive fungal disease who received adjunctive therapy with recombinant human macrophage colony-stimulating factor.

Mortality of bone marrow transplant (BMT) patients who develop invasive fungal infection is greater than 80%. Long-term follow-up of 46 consecutive BMT patients who received recombinant human macrophage colony-stimulating factor (rhM-CSF) as adjunctive therapy with standard antifungal treatment who were entered into phase I/II trials at The Fred Hutchinson Cancer Research Center is reported. rhM-CSF (100 micrograms/m2 to 2,000 micrograms/m2; Chiron/Cetus Corporation, Emeryville, CA) was administered from day 0 to 28 after determination of progressive fungal disease. Results of long-term follow-up of fungal infection, relapse, and survival were compared with 58 similar historical controls. Multivariable analysis of the patients who received rhM-CSF showed two factors that significantly correlated with poor survival: Karnofsky score < or = 20% and Aspergillus infection. Overall, survival of patients who received rhM-CSF was greater than that of historical patients (27% v 5%) and was entirely because of a 50% survival rate in patients with Candida infection and Karnofsky scores greater than 20%. Prospective, randomized, controlled trials to determine efficiency of rhM-CSF are indicated and should be directed at patients with invasive candidiasis.

Lymphocyte aging in bone marrow chimeras.

Chimeric mice provide a unique approach to the analysis of genetic factors associated with aging since cells with two genetically distinct backgrounds can be analyzed in the same animal. In this study, bone marrow chimeras were produced by reconstituting lethally irradiated female B6AF1 [(C57BL/6 female x A male)F1] mice with varying mixtures of T cell-depleted bone marrow cells from A (short-lived) and C57BL/6 (long-lived) mice. The phenotypic composition of the peripheral blood lymphocytes was analyzed using either a cytotoxicity assay or flow cytometry with indirect immunofluorescence. The percentage of A-derived lymphocytes in the peripheral blood following reconstitution was generally higher than the percentage of A bone marrow cells with which the irradiated mice were inoculated, suggesting that the cells from the A donor bone marrow were more efficient at marrow reconstitution than the cells from the C57BL/6 donor bone marrow. In order to determine whether the percentage of A- versus C57BL/6-derived cells changed with age in each animal, the chimeric mice were bled for phenotype analysis of peripheral blood lymphocytes between 2-6 months following reconstitution and at 2-3 month intervals until death. For most animals [93/127 (73%)], there was no consistent pattern of increase or decrease (> 20%) with regard to the percentage of A lymphocytes in the peripheral blood over time. However, in 34/127 (27%) of the chimeras, a change greater than 20% in the phenotypic composition of the peripheral blood lymphocytes was observed and these animals were considered unstable. Among these 34 unstable animals, 6 (18%) showed an overall increase in A-derived lymphocytes, 24 (71%) showed an overall decrease in A-derived lymphocytes, and 4 (12%) showed fluctuating increases and decreases over their lifespan. While the lifespans of the chimeric animals in these studies were considerably shorter than those reported for untreated mice of the same strain and gender, in these animals increased proportions of A cells were associated with significantly longer lifespans. In addition, the lifespan of the B6AF1 chimeric mice was a function of the proportion of A lymphocytes present in the peripheral blood over the course of the animal's life.

Long-term followup with the use of lyophilized dura mater for abdominal wall closure in children: report of 3 cases.

We report our experience with 3 children treated during infancy by abdominal wall reconstruction using lyophilized dura mater. Followup has been 36, 46 and 96 months postoperatively and they demonstrated adequate abdominal wall healing. One child has mild muscular diastasis, while 1 has completely healed. In 1 child a small defect developed in the repair, which was closed at a secondary procedure. Wound infection, dehiscence or herniation did not occur. There has been no evidence of Creutzfeldt-Jakob disease, which has been reported when allogenic dura was not obtained from registered tissue banks. Our experience with dura mater suggests that the material may be a useful adjunct in the repair and closure of complex abdominal defects.

Toward a methodology for moral decision making in medicine.

The failure of medical codes to provide adequate guidance for physicians' moral dilemmas points to the fact that some rules of analysis, informed by moral theory, are needed to assist in resolving perplexing ethical problems occurring with increasing frequency as medical technology advances. Initially, deontological and teleological theories appear more helpful, but criticisms can be lodged against both, and neither proves to be sufficient in itself. This paper suggests that to elude the limitations of previous approaches, a method of moral decision making must be developed incorporating both coherence methodology and some independently supported theoretical foundations. Wide Reflective Equilibrium is offered, and its process described along with a theory of the person which is used to animate the process. Steps are outlined to be used in the process, leading to the application of the method to an actual case.

Induction of HL-60 cell differentiation by water-soluble and nitrogen-containing conjugates of retinoic acid and retinol.

Retinoids induce the promyelocytic cell line, HL-60, to differentiate along the granulocytic pathway in vitro. A number of water-soluble and nitrogen-containing retinoids were synthesized in our laboratory [retinoyl-glucose (RAGL), retinyl-glucose (ROGL), retinoyl-adenosine (RADS), retinoyl-adenine (RAD), retinoyl-beta-glucuronide (beta RAG), and retinoyl-alpha-glucuronide (alpha RAG)]. These retinoids (10(-5) to 10(-8) M), as well as retinoic acid (RA) and retinol (ROL), were tested for their ability to induce the differentiation of HL-60 cells in vitro and to affect cell growth and viability during a 24- to 72-h incubation period. Differentiation was assessed by measuring the percentage of cells expressing the Mac-1 antigen on their cell surfaces. RA and the conjugates of RA were all quite active in inducing HL-60 cell differentiation, whereas ROL and ROGL had much less activity at equimolar concentrations. beta RAG, alpha RAG, RADS, and RAD were less toxic, whereas the glucose conjugates of retinol and retinoic acid (ROGL and RAGL) were both considerably more toxic than either RA or ROL at equimolar concentrations. All retinoids affected cell growth in a dose-dependent fashion. At 24 h, free RA or ROL was not detected in the cells after incubation with any of the retinoid conjugates.

Major histocompatibility complex antigen expression on lymphocytes from aging strain A mice.

Molecules encoded by the major histocompatibility complex (MHC) are crucial for the proper functioning of the immune response. In this study, the levels of class I and class II major histocompatibility antigens on lymphocytes from strain A mice were measured as a function of age. Class I protein levels increased significantly on both peripheral blood and spleen (T cells and B cells) lymphocytes with age. This increase in MHC class I protein levels was accompanied by an increase in class I mRNA levels. On the other hand, class II protein levels did not show a significant change with age. Moreover, while the percentage of class I-expressing spleen lymphocytes stayed at a steady-state level of 100% with age, the percentage of class II-expressing spleen lymphocytes decreased from 85% in young animals to 70% in old animals. This decrease was due to a decrease in the relative proportion of B cells compared to T cells in the spleen lymphocyte population of old mice. When class II mRNA levels were measured, it was found that these levels decreased markedly with age. Overall, it is clear that the regulation of MHC class I and class II expression changes with age in A strain mice. Since optimal levels of MHC expression are crucial for the proper functioning of cellular and humoral immune responses, it will be most interesting to understand how the control of MHC gene expression changes with age and whether MHC gene expression can be modulated in old individuals to restore better immune function.

Alteration of bronchoalveolar lavage cell populations following bleomycin treatment in mice.

Clinical use of the antitumor antibiotic bleomycin (BLM) is associated with the development of interstitial pulmonary fibrosis. Shortly after acute lung damage caused by intratracheal (it) administration of BLM to experimental animals there is an influx of inflammatory cells which are believed to modulate the process of fibrosis. This study was undertaken to determine what subpopulations of lymphocytes were in the bronchoalveolar lavage (BAL) cell population of C57BL/6J mice at various times after a single it dose of BLM and to determine whether BAL T-lymphocytes were activated after BLM treatment. The BAL lymphocyte population was analyzed by differential cell analysis and flow cytometry utilizing monoclonal antibodies specific for lymphocyte subpopulations. The majority of lymphocytes in the BAL of control and BLM-treated mice were T-lymphocytes, with less than 10% being B-cells. During the first 7 days after BLM the number of Lyt-2+ T-cells exceeded L3T4+ T-cells while in control mice the reverse was observed. The percentage of BAL lymphocytes expressing the IL-2 receptor did not change significantly at 3 and 7 days after BLM treatment, but was significantly decreased at Day 14. In contrast, the total number of lymphocytes expressing the IL-2 receptor was increased at all time points investigated. These results demonstrated that the majority of lymphocytes in the BAL were T-cells and that while the percentage of activated lymphocytes did not increase following BLM treatment, the absolute number did and this increased number of activated lymphocytes may be important in the disease process.

Effect of cytotoxic monoclonal antibody depletion of T-lymphocyte subpopulations on bleomycin-induced lung damage in C57BL/6J mice.

Treatment of cancer patients with the antitumor antibiotic bleomycin (BLM) is associated with lung damage which can progress to pulmonary fibrosis. Shortly after intratracheal (it) administration of BLM to experimental animals there is an influx of inflammatory cells into the lung. These inflammatory cells, consisting primarily of polymorphonuclear cells, monocytes and lymphocytes, are believed to modulate the pathogenesis of pulmonary fibrosis. The objective of the present study was to determine the role of specific T-lymphocyte subpopulations in this disease process following a single it administration of BLM to C57BL/6J mice. Specific in vivo T-lymphocyte subpopulation depletion was accomplished by multiple intraperitoneal administrations of cytotoxic monoclonal antibodies to mice prior to and following BLM administration. Acute lung damage was assessed by measuring levels of angiotensin-converting enzyme and total protein in the bronchoalveolar lavage fluid 7 days after BLM treatment while chronic fibrosis was assessed by total lung hydroxyproline 28 days after BLM. Although we were able to deplete lymph nodes and BAL of specific T-lymphocyte subpopulations we were unable to detect a difference in the extent or severity of either the acute or chronic stage of BLM-induced lung damage. These results suggest that BLM lung disease progresses unabated in C57BL/6J mice despite virtually complete depletion of either L3T4+ or Lyt-2+ T-lymphocytes. Although a greater than 80% decrease in Thy-1.2+ T-lymphocytes was accomplished, there was a residual population of Thy-1.2+ lymphocytes resistant to the cytotoxic antibody. It is possible, therefore, that this population of cells does play a role in the development of BLM lung disease.

Experience with a totally implantable venous device in children.

Venous access was attained in 15 children by use of a totally implantable central venous catheter and reservoir. Catheters were in place from 28 to 581 days, giving a cumulative experience of 4,094 days. Although they were well accepted by physicians, parents, and the children, they were not without major complications. These included extravasation of a chemotherapeutic agent in one, migration of the catheter tip to an unacceptable location in another, and catheter thrombosis and catheter-related sepsis in two each. The malpositioned catheter, one of the thrombosed catheters, and both infected catheters were removed. Ease of care, freedom from protruding tubing, and compatibility with normal activities are major positive features of the implantable devices that should be considered when deciding on the type of prolonged central venous access for use in children being treated with cancer.

Omphalocele: treatment options.

The charts of 62 infants born with an omphalocele were reviewed to determine both the timing and type of treatment that yielded the most satisfactory result. Infants born with an omphalocele can be divided into prognostic groups based on physical examination and simple roentgenograms. No single treatment method is applicable to or optimal for all types of omphalocele. Treatment options can be selected based on the presence or absence of conditions requiring emergency operation, the presence of complicating anomalies, and the size of the omphalocele. Although urgent evaluation of all infants born with an omphalocele is essential, emergency operation should be avoided in selected cases.

Immunotherapy of verrucae vulgares with dinitrochlorobenzene.

A study using daily topical applications of dinitrochlorobenzene on recalcitrant verrucae vulgares demonstrated this to be of practical value. Complete resolution of lesions occurred in 66% of 35 patients, with a complication rate of 24%. The results of other studies are reviewed and recommendations for use of this medication are given. DNCB therapy should, however, be reserved for use on recalcitrant lesions because of the complications associated with its usage.

Congenital lobar emphysema.

Congenital lobar emphysema is an uncommon but potentially life-threatening cause of respiratory distress in the newborn. The clinical picture and radiologic findings are diagnostic. Lobectomy in the distressed neonate is curative. In infants with onset of symptoms between one and four months of age surgery may not be necessary. Etiology and pathology of congenital lobar emphysema are not clear at present and require further elucidation.

The inhibitory effect of Corynebacterium parvum and Pasteurella multocida pretreatment on staphylococcal synovitis in turkeys.

Corynebacterium parvum and Pasteurella multocida were shown to be immunostimulants in turkeys, increasing the ability of whole blood to kill Staphylococcus aureus and prolonging the incubation time of experimental staphylococcal synovitis.