Pressure ulcers: critical considerations in prevention and management

Pressure ulcer development is a serious problem occurring predominately among elderly persons, who are confined to bed or chair. Factors associated with pressure ulcer development include: cerebrovascular accident, impaired nutritional intake, fecal incontinence, lymphocytopenia and a high comorbidity score. Implementation of preventative measures, such as: in-depth assessment for mobility, a pressure relieving device combined with adequate repositioning, thorough evaluation for nutritional status and urinary incontinence, significantly reduce pressure ulcer incidence. If the pressure ulcer is a partial thickness (Stage II) wound, the causative factors are probably friction and/or moisture. If the ulcer is full thickness (Stage III, IV) it is secondary to pressure and/or shearing forces. The development of wound infection is the most common complication. Osteomyelitis is not an uncommon occurrence and must be initially ruled out in all full thickness pressure ulcers. Surgical debridement of necrotic tissue is necessary prior to further treatment and /or assessments. Cultures and antibiotic therapy are indicated only upon evidence of infection (erythema, edema, cellulitis, osteomyelitis, leukocytosis, bandemia or fever). Topical pharmacologic agents may be used to prevent or treat infection but must be carefully controlled to avoid such adverse effects as toxicity to the wound, allergic reaction and development of resistant pathogens. Proper use of occlusive dressings increase patient comfort, enhance healing, decrease the possibility of infection, save time and reduce costs. A patient presenting an ulcer which fails to improve, or due to its size will take a great deal of time to heal, should be evaluated for surgical closure.     

Microfluorometry of nuclear acridine orange metachromasia in lymphocytes of thymus, spleen, and blood of AKR and random-bred mice.

Lymphocyte chromatin lability to acid hyrolysis was studied using acridine orange fluorescence metachromasia in a high-lymphocytic-leukemia-susceptibility strain (AKR) and random-bred mice (ICR). Comparisons were made of blood, thymus, and spleen lymphocytes between random-bred, "normal" AKR, and leukemic AKR animals. The leukemic mice were in the stages of the disease characterized by enlarged thymus and spleen but preceding massive elevation of blood lymphocytes. The ranges of the mean chromatin acid lability overlapped and were nearly identical in peripheral blood lymphocytes. However, thymic and splenic lymphocytes showed a marked rise in mean chromatic acid lability in the leukemic animals. The ranges of the mean values of this parameter were also found to be far greater in the lymphopoietic organs of normal AKR than in the random-bred mice. The data indicate that anatomically normal AKR animals of an age in which they are highly susceptible to spontaneous lymphocytic leukemia may contain a greater number of lymphoblasts in both the spleen and the thymus than do comparable random-bred mice. The implications of these findings are discussed in relation to strain differences and the concept of thymic origin of lymphocytic leukemia in mice.     

Molecular basis of cancer and clinical applications

This article attempts to show the vertiginous advances that exist today in the concept of what cancer is. The authors chose some multiple biologic concepts that have enabled the progress in the knowledge of this disease to occur at a speed no one could imagine until recently. Although the areas and biologic problems that remain to be solved are more numerous and complex than they expected, the basic fundamentals already partially understood and the multidisciplinary integration of the various medical specialties with biomolecular research enable physicians to face the next millennium with great optimism about the possibilities of therapeutic success, prevention, and effective early diagnosis.     

Pulmonary cystic adenomatoid malformation with anomalous vascularization with systemic origin

We report an infant with the diagnosis of Congenital Cystic Adenomatoid Malformation. He was operated and we found an abnormal systemic blood supply associated in that lobe. We make a review of the literature, and we make a distinction between this rare combination and others like pseudo pulmonary sequestration, or Congenital Cystic Adenomatoid Malformation associated to pulmonary sequestration.     

Intravenous delivery of adenovirus-mediated soluble FLT-1 results in liver toxicity.

PURPOSE: Vascular endothelial growth factor (VEGF) is a potent angiogenic agent and plays a major role in tumor growth and metastases. We have previously reported the locoregional (i.p.) delivery of adenovirus-mediated antiangiogenic soluble FLT-1 (sFLT-1; a naturally encoded potent VEGF antagonist) gene therapy to inhibit VEGF action in a murine ovarian carcinoma model. This study was predicated on the fact that systemic delivery of sFLT-1 might allow an approach for therapy of disseminated tumor. The purpose of this study is to test the effects of i.v. delivered, adenovirus-mediated sFLT-1 on the survival duration in a murine ovarian tumor model and to evaluate the safety of i.v.-delivered versus i.p.-delivered adenovirus-mediated sFLT-1 in non-tumor-bearing mice. EXPERIMENTAL DESIGN: To determine the effects of i.v.-administered adenovirus-mediated sFLT-1 on survival duration of mice bearing i.p. human ovarian tumors, an E1A/B-deleted, (replication-deficient) infectivity-enhanced recombinant adenovirus AdRGDGFPsFLT-1 encoding cDNA for both sFLT-1 and GFP (green fluorescent protein), a control adenovirus AdRGDGFP encoding GFP alone, or PBS was delivered i.v. The therapeutic effect of sFLT-1 was evaluated by survival duration of the mice. Furthermore, the safety of i.v.- or i.p.-delivered adenovirus-mediated sFLT-1 was evaluated by administering AdRGDGFPsFLT-1, AdRGDGFP, or PBS either i.v. or i.p. into non-tumor-bearing mice. Adenovirus-mediated gene expression was determined by determining GFP expression using fluorescent microscopy and by assessing sFLT-1 expression in liver, lungs, spleen, and kidneys by immunohistochemistry using anti-FLT-1 monoclonal antibody. Systemic levels of sFLT-1 were evaluated by ELISA and the toxicity was evaluated by histopathology. RESULTS: The i.v. delivery of AdRGDGFPsFLT-1 in the ovarian tumor model resulted in a shorter duration of survival of the mice as compared with the control group. Furthermore, in the safety evaluation experiment, i.v. administration of AdRGDGFPsFLT-1 in non-tumor-bearing mice principally localized to the liver. This localization lead to sFLT-1 overexpression, mainly in the liver, resulting in hemorrhage and tissue toxicity. However, i.p. delivery of AdRGDGFPsFLT-1 did not localize principally to the liver, leading to negligible expression of sFLT-1, and no intrahepatic hemorrhage or toxicity was observed. The i.v. delivery of the control virus AdRGDGFP also principally localized to the liver, leading to GFP expression mainly in the liver. However, neither hemorrhage nor morphological cytotoxicity was observed. i.p. delivery of AdRGDGFP resulted in ectopic localization to the liver with very little GFP expression and no toxicity. These results suggest that overexpression of sFLT-1 in the liver as a result of i.v. delivery is hepatotoxic. CONCLUSIONS: Our results suggest that i.v. delivery of the sFLT-1 gene via replication-deficient, infectivity-enhanced recombinant adenoviral vectors will result in overexpression of sFLT-1 in the liver leading to unacceptable hepatotoxicity. Tumor-specific targeting of the vectors and tumor-specific expression strategies should be used to ensure a clinically useful antiangiogenesis gene therapy.     

Molecular and functional characterization of porcine LFA-1 using monoclonal antibodies to CD11a and CD18

Abstract: We describe in this report the production and characterization of monoclonal antibodies (mAb) to the swine homologues of CD11a and CD18 antigens, and their use for phenotypic and functional analysis of porcine leukocytes. Monoclonal antibodies BL1H8 and BL2F1 precipitated two bands of approximately 170 and 95 kDa, whereas mAb BA3H2 brought down three bands of 170, 155 and 95 kDa, from alveolar macrophage lysates. Clearance of macrophage lysates with mAbs BL1H8 and BL2F1 resulted in complete removal of the 170-kDa band. The cell distribution of the molecules recognized by these mAbs was similar to that of human LFA-1. It was found on all leukocytes, although its expression varied among the different leukocyte subpopulations, with monocytes, granulocytes and a subset of CD8⁺ cells expressing the highest levels. Cross-blocking studies showed that these antibodies recognize different epitopes on porcine LFA-1. Both anti-LFA-1 mAbs strongly inhibited the mitogenic response of PBMC to ConA, whereas the anti-CD18 mAb had no effect. These anti-LFA-1 mAbs also inhibited the mixed lymphocyte reaction (MLR) and the NK cell-mediated lysis of K-562 cells.