Granulocyte colony-stimulating factor has differing effects comparing intravascular versus extravascular models of sepsis

BACKGROUND: Previously, neutrophil stimulation with granulocyte colony-stimulating factor (G-CSF) pretreatment increased survival rates in canines challenged with intraperitoneal or intrabronchial Escherichia coli and in rats challenged with intrabronchial Staphylococcus aureus. We investigated whether G-CSF pretreatment would be beneficial with intravascular challenge in these models. METHODS: Animals were randomized to G-CSF or placebo pretreatment followed by intravenous E. coli challenge in canines (n = 24) or intravenous or intrabronchial S. aureus challenge in rats (n = 273). All animals were treated with antibiotics. RESULTS: In canines, G-CSF before intravenous E. coli did not decrease mortality rates (7 of 12 [58%] G-CSF vs. 5 of 12 [42%] controls), which contrasted with prior reductions during extravascular infection (10 of 35 [29%] G-CSF vs. 37 of 65 [57%] controls). Consistent with the present and previously published studies in canines, in rats, G-CSF decreased mortality rates with intrabronchial S. aureus (22 of 90 [24%] G-CSF vs. 26 of 51 [51%] controls, p = 0.009) but did not decrease them with intravenous infection (34 of 67 [50%] G-CSF vs. 27 of 65 [42%] controls, p = 0.2) in patterns that were very different (p = 0.005 for the effects of G-CSF with intravascular vs. intrabronchial S. aureus). CONCLUSION: In contrast to extravascular infection, sepsis with intravascular E. coli in canines and S. aureus in rats may not provide a compartmentalized nidus of bacteria on which G-CSF-stimulated neutrophils can exert a beneficial antimicrobial effect. Extrapolated clinically, a proinflammatory agent like G-CSF may be most beneficial with sepsis related primarily to a compartmentalized extravascular site of infection.     

Disease laterality,eye dominance,and visual handicap in patients with unilateral full thickness macular holes

AIM: To investigate the association between visual handicap, laterality, and historical eye dominance in patients presenting with unilateral full thickness macular holes (FTMH). METHODS: Consecutive patients presenting with unilateral FTMH and no other visually significant ocular pathology including abnormalities of binocular vision were included. A questionnaire and case note review were performed to determine the mode of presentation, presence of symptomatic binocular interference, historically dominant eye, and whether they elected to undergo surgery. RESULTS: 44 eyes of 44 patients fulfilled the inclusion criteria. 21 (48%) affected eyes were right sided and 56% of FTMH were in the historically dominant eye. 76% of FTMH in historically dominant eyes presented symptomatically compared to 36% in non-dominant eyes (p= 0.003). 72% of patients with FTMH affecting their historically dominant eye were aware of binocular interference in day to day binocular viewing compared with 21% when the FTMH was in the non-dominant eye (p= 0.001). 23 (52%) patients elected to undergo surgery, of whom 18/23(78%) had FTMH in their historically dominant eye (p= 0.0003). CONCLUSION: This study suggests that eye dominance may be an important determinant of the visual handicap suffered by patients with unilateral FTMH.     

Environmental radiation measurements using TLD-900 at the King Saud University Campus, Riyadh, Saudi Arabia

To determine the baseline environmental radiation and resulting population exposure, natural background levels at the King Saud University campus were measured using CaSO4:Dy (TLD-900) discs. Measurements were made 1 m above ground level at 10 locations. Two different calculational methods were utilized to account for signal fading. In the first method, a fading correction factor was determined and used separately. In the second method, a separate correction factor for fading was not required because the determined calibration factor was carrying this correction. Results of the two methods were similar. Measurements were performed on a quarterly basis for a 2-y period (January 1988 to December 1989). The annual average dose rate was 565.4 +/- 27.1 mu Gy y-1 in air.     

Regulation of diffusion-chamber granulopoiesis by colony-stimulating factor

Studies were undertaken to examine the role of colony-stimulating factor (CSF) in controlling murine peritoneal diffusion-chamber (DC) granulopoiesis. Serum CSF was unchanged for 1-3 days after 700-750 rad total body irradiation. Variable increments were noted on the fourth and seventh days after irradiation. DC CSF increased four- to fivefold over serum activity within 24 h of implantation in control mice. An eight- to tenfold increment over serum levels was noted in DC CSF from irradiated mice. Both serum and DC CSF were neutralized completely by repeated injections of anti-CSF serum. DC granulopoiesis was studied by immobilizing marrow cells in plasma clots in peritoneal DC. Repetitive administration of anti-CSF serum or a purified monospecific anti-CSF antibody caused a marked reduction in DC granulopoiesis. This was characterized by a decrease in both the number and size of granulocyte colonies, with a 40%-80% decrease in total granulocytes per chamber. These findings indicate that the granulopoiesis observed in the DC of irradiated hosts is associated with an increase in local rather than systemic CSF production. Neutralization of the CSF reduces proliferation of the granulocyte progenitor cell and maturation of more differentiated granulocytic cells.     

Chronic cicatrizing conjunctivitis in a patient with ocular cicatricial pemphigoid and fatal Wegener granulomatosis

PURPOSE: To describe a case of chronic cicatrizing conjunctivitis in a patient with ocular cicatricial pemphigoid and Wegener granulomatosis. METHODS: Observational case report. A retrospective study. RESULTS: An 80-year-old man presented with chronic cicatrizing conjunctivitis, peripheral corneal thinning, and Wegener granulomatosis, which were diagnosed by his referring physician based on clinical (recurrent epistaxis, sinus congestion) and histopathologic features of nasal mucosa (granulomatous inflammation, vasculitis). A conjunctival biopsy performed by us disclosed features of active Wegener granulomatosis and ocular cicatricial pemphigoid, which indicate lack of control of both diseases with methotrexate treatment. The patient died of pulmonary complications from Wegener granulomatosis 1 week after our evaluation. CONCLUSION: Ocular cicatricial pemphigoid and Wegener granulomatosis are both potentially fatal autoimmune diseases. Ocular involvement in Wegener granulomatosis indicates poor control of the underlying systemic condition and is a marker for active vasculitis, which indicates the need for treatment with cyclophosphamide.     

Zur Topographie der Brustorgane beim menschlichen Fetus

Ohne ZusammenfassungMit 10 Textabbildungen.Dissertation der medizinischen Fakultät der Universität Zürich.