BACKGROUND: This study was to clarify the effects of gabexate mesilate (Foy(R)), a synthetic protease inhibitor, on endotoxin induced acute lung injury in rabbit. METHODS: Animals were randomly assigned to one of four groups: saline only (n = 7), saline and Escherichia coli endotoxin 5 mg/kg over 30 mins (n = 7), Foy(R) 1 mg/kg bolus, followed by infusion of Foy(R) at 1 mg/kg/h and endotoxin (n = 7), Foy(R) 2 mg/kg bolus, followed by infusion of Foy(R) at 2 mg/kg/h and endotoxin (n = 7). Infusion of saline or Foy(R) was started 0.5 hour before the start of infusion of saline or endotoxin and continued for 6.5 hours. At the end infusion animals were sacrificed, and the wet to dry (W/D) weight ratio of lung, lung injury score and leukocyte counts, percentage of polymorphonuclear leukocyte (PMNL), and concentrations of albumin and interleukin-8 (IL-8) in bronchoalveolar lavage fluid (BALF) were evaluated. RESULTS: Endotoxin decreased the PaO2 and peripheral blood leukocyte and platelet counts. And it increased the W/D weight ratio of lung, lung injury score and leukocyte counts, percentage of PMNL, and concentrations of albumin and IL-8 in BALF. Foy(R) attenuated all these changes except the decreased peripheral blood leukocyte count. CONCLUSIONS: These findings suggest that Foy(R) attenuates endotoxin-induced acute lung injury in rabbit by inhibiting neutrophil, IL-8 and platelet responses which may play a central role in sepsis related lung injury.
Acute Lung Injury* ; Animals ; Blood Platelets ; Bronchoalveolar Lavage Fluid ; Escherichia coli ; Gabexate* ; Interleukin-8 ; Leukocyte Count ; Leukocytes ; Lung ; Lung Injury ; Neutrophils ; Platelet Count ; Protease Inhibitors ; Sepsis

Diphenylhydantoin (DPH) is one of the most widely used anticonvulsants for treatment and prevention of seizures. However it is frequently associated with drug-induced leukopenia. Hypersensitivity reactions to phenytoin are well recognized and can be severe. Phenytoin is associated with serious hematologic side effects such as agranulocytosis, thrombocytopenia, red cell aplasia and hemolytic anemia, either through humoral or cell-mediated immunemechanism. We describe a 57-year-old male patient who developed a severe granulocytopenia while taking phenytoin for 66 days in the total amount of 21.6 gram. Bone marrow examination showed isolated depletion of myeloid elements. After 10 days of phenytoin withdrawal and G-CSF treatment, the patient recovered from granulocytic suppression. Using in vitro culture, marrow suppression associated with phenytoin therapy was felt to be non-immune mediated marrow suppression.
Agranulocytosis ; Anemia, Hemolytic ; Anticonvulsants ; Bone Marrow Examination ; Bone Marrow* ; Granulocyte Colony-Stimulating Factor ; Humans ; Hypersensitivity ; Leukopenia ; Male ; Middle Aged ; Phenytoin* ; Seizures ; Thrombocytopenia

Chronic hemodialysis patients frequently experience hemodialysis(HD)-related side effects caused by excessive ultrafiltration and abrupt change of osmolality. Sodium ramping in HD is known to reduce ultrafiltration-related side effects, but it frequently induces symptoms related to sodium overload. We wanted to know the relationship between blood volume changes and the side effects related to ultrafiltration during hemodialysis and whether we can individualize various sodium ramping methods according to the effect of change in blood volume( BV) and side effects of sodium ramping. We studied 9 hypotension-prone patients during HD. The duration of the study lasted for 5 weeks, each week using different sodium ramping protocols: protocol 1; dialysate [Na+] of 140mEq/L, protocol 2; dialysate [Na+] same as the predialysis serum [Na+], protocol 3; dialysate [Na+] was 20mEq/L greater than that of the patient's serum for 1hr, 10mEq/L greater than patient's serum [Na+] for 2hr and then the same as patient's serum [Na+] for the last 1hr, protocol 4; at the beginning of dialysis, dialysate sodium was ramped to 20mEq/L above the patient's serum sodium and then on a straight linear fashion lowered to the predialysis serum [Na+] at the end of dialysis, protocol 5; sodium was constantly ramped to 10 mEq/L above serum [Na+]. We measured the BV with Crit-Line IIR(In-Line Diagnostics, Corp., Riverdale, USA), the blood pressure during each HD and interdialytic weight gain. We documented subjective symptoms which occurred during the 5 treatment protocols by patient's questionnaire after each HD. The results were as follows. 1) The mean age of the patients(M:F=3:6) was 54.1years and 6 patients were diabetics. 2) There was no significant difference in the BV among the 5 protocols in both whole study population and individual. Neither was there a statistically significant difference in the BV with respect to hypotension during HD. 3) There were no episodes of hypotension(P value <0.001) with protocols 3, 4, 5 compared to protocols 1 and 2. 4) Three patients during protocols 4 and 5 experienced more thirst after HD than during protocol 1 and one patient during protocol 4, 5 had more interdialytic weight gain than the protocol 1. As a whole, patients while on protocol 4 & 5 experienced more thirst than protocol 1 but patients during protocol 3 experienced the same degree of thirst as protocol 1. In summary, sodium ramping reduced HD-related side effects but this benefit could not be explained on the basis of blood volume change measured by the Crit-Line IIR. Protocol 3 may be more appropiate sodium ramping method in 4 of the 9 patients. These data suggest that protocol 3 may be used before protocol 4, 5 when we apply sodium ramping to the patients who frequently have hypotension during HD.
Architectural Accessibility* ; Blood Pressure ; Blood Volume* ; Clinical Protocols ; Dialysis ; Humans ; Hypotension ; Osmolar Concentration ; Renal Dialysis* ; Sodium* ; Thirst ; Ultrafiltration ; Weight Gain ; Surveys and Questionnaires