ABSTRACT
OBJECTIVE: To examine the expression of molecules known to participate in early T cell receptor (TCR)/CD3 signaling in peripheral blood (PB) T lymphocytes from patients with systemic lupus erythematosus (SLE). METHODS: Signaling molecules were analyzed by immunoprecipitation and Western blotting of unstimulated PB T lymphocyte cell lysates from SLE patients, non-SLE disease controls, and healthy controls. Flow cytometry was used for analysis of the expression of membrane markers in intact cells. RESULTS: PB T lymphocytes from SLE patients showed diminished levels of TCRzeta chains. This was not due to trapping of these molecules in the cytoskeleton, nor was it dependent on the presence of monocyte/macrophages. There was normal expression of CD3epsilon chains and normal assembly of TCR/CD3 complexes in membranes. We observed a lack of expression of TCRzeta chains in in vitro cultures of SLE T cells, and reversal of the defective expression in some patients by culturing T cells in the presence of NH4Cl. CONCLUSION: Blood lymphocytes from SLE patients have a diminished expression of TCRzeta chains that may be related to enhanced degradation in the lysosomal compartment. The defective expression of these molecules may alter signal transduction via the CD3 pathway and contribute to abnormal T cell responses in T lymphocytes from SLE patients.
Subject(s)
Lupus Erythematosus, Systemic/blood , Membrane Proteins/blood , Receptors, Antigen, T-Cell/blood , T-Lymphocytes/chemistry , Adolescent , Adult , Cell Culture Techniques , Cell Movement , Electrophoresis , Female , Humans , Lymphocyte Activation/immunology , Lysosomes/metabolism , Macrophages/physiology , Male , Middle Aged , Monocytes/physiology , Proteins/metabolism , T-Lymphocytes/cytology , T-Lymphocytes/immunologyABSTRACT
OBJECTIVE: To investigate the effect of i.v. administration of fluids on the furosemide-induced reduction in right atrial pressure (RAP) and relative change in blood volume (BV) of splenectomized mares. ANIMALS: 5 splenectomized mares. PROCEDURE: RAP was measured by use of a micromanometer placed in the right atrium. Jugular venous blood was collected for measurement of hematocrit, plasma total protein concentration, and hemoglobin concentration. Right atrial pressure was recorded and blood samples were collected immediately before furosemide (1 mg/kg of body weight, i.v.) administration, then every 15 minutes for 240 minutes. Beginning 120 minutes after furosemide administration, polyionic fluids (lactated Ringer's solution) were administered (2 L q 15 min) for 120 minutes. RESULTS: Furosemide induced a significant (P < 0.05) decrease in mean RAP (7.6 +/- 1.5 and 3.2 +/- 1.2 mm of Hg before and 15 minutes after furosemide administration, respectively), and BV (8.4 +/- 1.1 % by 15 minutes). Polyionic fluid administration restored RAP and BV. The volume of polyionic fluids administered (32 +/- 2 ml/kg) was not significantly different from the volume of urine produced (38 +/- 7.8 mg/kg). Difference was not apparent in the relation between change in BV and RAP before or after fluid administration. CONCLUSIONS: The effect of furosemide on RAP of horses is mediated in large part by furosemide-induced reduction in BV. However, an effect of furosemide on venous compliance cannot be excluded as contributing to the reduction in RAP.
Subject(s)
Blood Pressure/drug effects , Diuretics/pharmacology , Furosemide/pharmacology , Horses/physiology , Isotonic Solutions/pharmacology , Analysis of Variance , Animals , Blood Pressure/physiology , Blood Proteins/analysis , Blood Volume/drug effects , Female , Heart Rate/drug effects , Heart Rate/physiology , Hematocrit/veterinary , Hemoglobins/analysis , Infusions, Intravenous/veterinary , Isotonic Solutions/administration & dosage , Ringer's Solution , Splenectomy/veterinaryABSTRACT
OBJECTIVE: To describe changes in blood constituents of horses after oral and i.v. administration of sodium bicarbonate (NaHCO3), and to determine whether the changes are dose dependent. ANIMALS: 6 adult Standardbred mares. PROCEDURE: 3 oral doses (1,500, 1,000, and 250 mg/kg of body weight) or 1 intravenous dose (250 mg/kg, 5% solution) of NaHCO3 in 3 L of water, or water (3 L orally), were given to the mares; then changes in blood constituents were measured. Access to food and water was denied during the experiment. Blood samples were collected immediately before treatment and at hourly intervals for 12 hours after treatment, and were analyzed for blood gas tensions; serum osmolality; serum sodium, potassium, chloride, and creatinine concentrations; PCV; and total solids concentration in plasma. RESULTS: All NaHCO3 treatments induced significant (P < 0.05) metabolic alkalosis, hypernatremia, hypokalemia, and hyperosmolality for at least 8 hours. In mares given the 1,500- and 1,000-mg doses of NaHCO3 orally, hypercapnia persisted for at least 12 hours, whereas hypercapnia lasted 2 hours in mares given the 250-mg dose orally or i.v. (P < 0.05). A tendency for reduction in PCV, proteins in plasma concentration, and serum concentration of chloride was observed 1 hour after i.v. administered doses of NaHCO3. CONCLUSIONS: Oral or i.v. administration of NaHCO3 (> or = 250 mg/kg) to resting horses without ad libitum access to water induces significant and persistent acid-base and electrolyte changes.
Subject(s)
Horses/blood , Sodium Bicarbonate/pharmacology , Acid-Base Equilibrium , Administration, Oral , Alkalosis/blood , Alkalosis/chemically induced , Alkalosis/veterinary , Animals , Blood Gas Analysis , Blood Proteins/analysis , Chlorides/blood , Creatinine/blood , Dose-Response Relationship, Drug , Female , Hydrogen-Ion Concentration , Hyperkalemia/blood , Hyperkalemia/chemically induced , Hyperkalemia/veterinary , Hypernatremia/blood , Hypernatremia/chemically induced , Hypernatremia/veterinary , Injections, Intravenous/veterinary , Osmolar Concentration , Potassium/blood , Sodium/blood , Sodium Bicarbonate/administration & dosage , Sodium Bicarbonate/adverse effects , Time FactorsABSTRACT
OBJECTIVE: To describe changes in renal function of horses after oral and i.v. administration of sodium bicarbonate (NaHCO3) and to determine whether changes are dose dependent. ANIMALS: 6 Standardbred mares. PROCEDURE: Blood and urine samples for determination of renal function were collected immediately before and at hourly intervals for 12 hours after administration of each of 3 oral doses (1,500, 1,000 and 250 mg/kg of body weight, in 3 L of water) and 1 i.v. dose (250 mg/kg, 5% solution) of NaHCO3, or water (3 L orally). RESULTS: NaHCO3 induced increases in urine flow; electrolyte-free water reabsorption; urine concentrations of sodium and bicarbonate; fractional excretion of sodium, potassium, chloride, and bicarbonate; urinary excretion and clearance of sodium and bicarbonate; urine pH and anion gap; and mean plasma concentration of antidiuretic hormone. NaHCO3 induced attenuation in reduction with time of urine excretion and clearance of potassium, chloride, and osmoles, and induced reduction in urine osmolality. Plasma aldosterone and atrial natriuretic peptide concentrations and glomerular filtration rate were not modified. CONCLUSIONS: Renal responses to NaHCO3 load emphasize conservation of plasma volume and reestablishment of acid-base balance over control of hyperosmolality by diuresis, natriuresis, and increased bicarbonaturia. These responses imply a large fluid shift from the extravascular space to the vascular compartment, which was eliminated via diuresis, thus preventing hypervolemia.
Subject(s)
Horses/physiology , Kidney/drug effects , Sodium Bicarbonate/pharmacology , Acid-Base Equilibrium , Administration, Oral , Aldosterone/blood , Animals , Atrial Natriuretic Factor/blood , Bicarbonates/urine , Chlorides/urine , Dose-Response Relationship, Drug , Female , Fluid Shifts , Glomerular Filtration Rate , Horses/metabolism , Hydrogen-Ion Concentration , Injections, Intravenous/veterinary , Kidney/physiology , Osmolar Concentration , Potassium/urine , Radioimmunoassay/veterinary , Sodium/urine , Sodium Bicarbonate/administration & dosage , Time Factors , Vasopressins/bloodABSTRACT
Cervical meningomyelocele, spina bifida, and hydrocephalus were diagnosed in a newborn miniature colt that was unable to stand and had a cystic mass in the caudal portion of the dorsal cervical region. Results of physical examination and ultrasonographic imaging of the brain supported the diagnosis of hydrocephalus. Results of radiographic evaluation of the vertebral column were consistent with spina bifida at C5-C6. Fluid aspirated from the cervical mass resembled CSF. Radiography of the cervical region after injection of iohexol into the mass revealed herniation of the spinal cord through a large bony defect, supporting the diagnosis of spina bifida and meningomyelocele. Meningomyelocele, spina bifida, and hydrocephalus are interrelated congenital anomalies in other species. Meningomyelocele should be suspected in foals that have neurologic abnormalities, especially if they have other congenital anomalies and a fluid-filled mass along the dorsal midline.
Subject(s)
Horse Diseases/diagnosis , Hydrocephalus/veterinary , Meningomyelocele/veterinary , Spinal Dysraphism/veterinary , Animals , Cervical Vertebrae/diagnostic imaging , Cervical Vertebrae/pathology , Horse Diseases/diagnostic imaging , Horse Diseases/pathology , Horses , Hydrocephalus/complications , Hydrocephalus/diagnosis , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/pathology , Male , Meningomyelocele/complications , Meningomyelocele/diagnosis , Radiography , Spinal Dysraphism/complications , Spinal Dysraphism/diagnosis , Thoracic Vertebrae/diagnostic imaging , Thoracic Vertebrae/pathologyABSTRACT
The clinical and clinicopathologic characteristics of fatal necrotizing enterocolitis were examined in 16 horses (age 4 months to 12 years). At initial presentation, 8 of 16 horses were pyrexic (median temperature, 38.4 degrees C; range, 33.8 to 40.6 degrees C); all 16 were tachycardic (median heart rate, 93 bpm, range, 66 to 138 bpm); 13 of 16 were tachypneic (median heart rate, 36 bpm, range, 16 to 80 bpm), dehydrated, and had discolored mucous membranes. All horses that were pyrexic were also tachycardic and tachypneic. PCV was high (> 45%) in 14 horses. Six horses were leukopenic (< 5,000 cells/microL); 12 were neutropenic (< 2,300 cells/microL), and 14 had > 100 band neutrophils/microL. Twelve horses were acidemic (pH < 7.37; range, 6.88 to 7.33) and the venous bicarbonate concentration was low (< 23 mEq/L) in 14 horses. Median anion gap in 16 horses was 31.5 mEq/L (> 15 mEq/L in 15 horses). Eleven of 16 horses were hyponatremic (< 137 mEq/L), 1 horse was hypernatremic (> 143 mEq/L), 3 were hypokalemic (< 3.2 mEq/L), 6 were hyperkalemic (> 4.5 mEq/L), and 14 were hypochloremic (< 98 mEq/L). Serum creatinine concentrations were high (> 1.4 mg/dL) in 15 horses. Abdominal fluid was examined in 12 horses 4 had total protein concentrations > 2.5 g/dL and 6 had nucleated cell counts > 5,000/ microL and < 10,000/microL; none had > 10,000/microL. Eight of 12 samples revealed a nondegenerate neutrophilia (> 50%). Abdominal fluid collected from 4 horses immediately before death was normal in 2 horses and indicative of suppurative inflammation in 2. All 8 horses tested had low or nonexistent serum immunofluorescent antibody titers to Ehrlichia risticii. Four of 16 horses had Salmonella spp isolated from feces or tissues. All 16 horses either died (5 of 16; 31%) or were euthanized because of a grave prognosis. Median time to death was 45.5 hours (range, 7 to 113 hours) from the time of admission. Death was preceded by severe abdominal pain in 14 horses. Fatal necrotizing enterocolitis of horses is characterized by a brief course, profound dehydration, electrolyte derangements, acid-base abnormalities, and terminally, severe abdominal pain. Abdominal fluid analysis was frequently not indicative of the severity of disease.