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Biomedical subjects

L G King

Publications and source records attributed to L G King.

At least 19 recordsLinked to original sources

The gramicidin-based biosensor: a functioning nano-machine.

Biosensors combine a biological recognition mechanism with a physical transduction technique. In nature, the transduction mechanism for high sensitivity molecular detection is the modulation of the cell membrane ionic conductivity through specific ligand-receptor binding-induced switching of ion channels. This effects an inherent signal amplification of six to eight orders of magnitude, corresponding to the total ion flow arising from the single channel gating event. Here we describe the first reduction of this principle to a practical sensing device, which is a planar impedance element composed of a macroscopically supported synthetic bilayer membrane incorporating gramicidin ion channels. The membrane and an ionic reservoir are covalently attached to an evaporated gold surface. The channels have specific receptor groups attached (usually antibodies) that permit switching of gramicidin channels by analyte binding to the receptors. The device may then be made specific for the detection of a wide range of analytes, including proteins, drugs, hormones, antibodies, DNA, etc., currently in the 10(-7)-10(-13) M range. It also lends itself readily to microelectronic fabrication and signal transduction. By adjusting the surface density of the receptors/channel components during fabrication, the optimum sensitivity range of the device may be tuned over several orders of magnitude.

Anti-Bacterial Agents

Clinical manifestations and associated disease syndromes in dogs with cranial vena cava thrombosis: 17 cases (1989-1996).

OBJECTIVE: To characterize cranial vena cava thrombosis in dogs with regard to signalment, clinical manifestation, potential inciting causes, treatment, and outcome. DESIGN: Retrospective study. ANIMALS: 17 dogs with a cranial vena cava thrombus. PROCEDURE: Medical and necropsy records were reviewed for signalment, potential causes of thrombus formation, diagnosis, clinicopathologic findings, treatment, and outcome. RESULTS: A signalment predisposition was not found. Ten dogs had cranial vena cava syndrome, and 10 had a pleural effusion. Ten dogs were dyspneic, and 5 had palpable jugular thrombi. Predisposing conditions identified were presumed immune-mediated hematologic disease and corticosteroid administration (6 dogs), sepsis (6), protein-losing nephropathy (2), neoplasia (2), and cardiac disease (1). Central venous catheterization was implicated as a contributing cause. Thrombocytopenia was the most consistent clinicopathologic finding, and ultrasonography was helpful in confirming the diagnosis. Treatment varied, but 15 of the 17 dogs died or were euthanatized within 20 days of clinical manifestation of the thrombus. At necropsy, thrombi were found in other organs, mainly the right atrium, jugular veins, and pulmonary arteries. CLINICAL IMPLICATIONS: Prognosis is poor for dogs with cranial vena cava thrombosis associated with clinical signs. Use of central venous catheters should be avoided in dogs with predisposing diseases such as immune-mediated disease, sepsis, protein-losing nephropathy, neoplasia, and cardiac disease.

Anemia, Hemolytic, Autoimmune

Acute fulminating myasthenia gravis in five dogs.

Acute fulminating myasthenia gravis (MG) was diagnosed in 5 dogs. Acute fulminating generalized MG in dogs is characterized by sudden onset of megaesophagus and frequent regurgitation of large volumes of fluid. Generalized muscle weakness can worsen and lead to recumbency within days. Despite appropriate supportive care, weakness is not alleviated by rest. Respiratory failure caused by aspiration pneumonia and loss of strength in muscles involved with respiration is a common cause of death. In dogs with acute onset of regurgitation, MG should be considered as a differential diagnosis. Clinicians should be aware of the risk of rapid progression to quadriparesis if aspiration pneumonia develops.

Animals

Fluid therapy in shock.

The goal of treatment for all types of shock is the improvement of tissue perfusion and oxygenation. The mainstay of therapy for hypovolemic and septic shock is the expansion of the intravascular volume by fluid administration, including crystalloids, colloids, and blood products. Frequent physical examinations and monitoring enable the clinician to determine the adequacy of tissue oxygenation and thus the success of the fluid therapy.

Animals

A biosensor that uses ion-channel switches.

Biosensors are molecular sensors that combine a biological recognition mechanism with a physical transduction technique. They provide a new class of inexpensive, portable instrument that permit sophisticated analytical measurements to be undertaken rapidly at decentralized locations. However, the adoption of biosensors for practical applications other than the measurement of blood glucose is currently limited by the expense, insensitivity and inflexibility of the available transduction methods. Here we describe the development of a biosensing technique in which the conductance of a population of molecular ion channels is switched by the recognition event. The approach mimics biological sensory functions and can be used with most types of receptor, including antibodies and nucleotides. The technique is very flexible and even in its simplest form it is sensitive to picomolar concentrations of proteins. The sensor is essentially an impedance element whose dimensions can readily be reduced to become an integral component of a microelectronic circuit. It may be used in a wide range of applications and in complex media, including blood. These uses might include cell typing, the detection of large proteins, viruses, antibodies, DNA, electrolytes, drugs, pesticides and other low-molecular-weight compounds.

Biosensing Techniques

Measurement of urinary urea nitrogen content as an estimate of the amount of total urinary nitrogen loss in dogs in intensive care units.

OBJECTIVE: To investigate whether urinary urea nitrogen (UUN) content can be used to accurately estimate total urinary nitrogen content in hospitalized dogs. DESIGN: Prospective, cohort study. ANIMALS: 24 client-owned dogs admitted to an intensive care unit of a veterinary teaching hospital. PROCEDURE: Indwelling urinary catheters and closed collection systems were placed for the purpose of monitoring urine output. Urine was collected during a 24-hour period from each dog. For each collection, the total volume was measured. Urine was analyzed for urea nitrogen content at an in-house laboratory, using standard methods for determination of BUN content. Total urinary nitrogen content was determined by another laboratory, using Kjeldahl's method. Correlation between UUN content and total urinary nitrogen content was evaluated by use of linear regression analysis. RESULTS: Total urinary nitrogen content adjusted for metabolic body weight ranged from 0.21 to 2.21 g/ kg0.75/d (mean +/- SD, 0.81 +/- 0.46 g/kg0.75/d). Adjusted UUN content ranged from 0.05 to 1.50 g/kg0.75/d (0.54 +/- 0.38 g/kg0.75/d). Total urinary nitrogen content was highly correlated with UUN content (R2, 0.88; P < 0.001). CLINICAL IMPLICATIONS: Measurement of UUN content can be used to estimate total urinary nitrogen content in a clinical setting. Furthermore, critical illness in dogs is associated with substantial catabolism of endogenous proteins.

Animals

Identification and minimization of nonideal binding effects in BIAcore analysis: ferritin/anti-ferritin Fab' interaction as a model system.

The interaction of human spleen ferritin with a monoclonal antibody Fab' fragment has been studied as a model system for BIAcore analysis. In particular, the influence of nonideal binding effects has been examined both experimentally and by the theoretical simulation of sensorgram curves. Mass transfer effects were found to have a small but significant influence on the observed binding kinetics of the ferritin/antiferritin Fab' interaction; however, this nonideal behavior could be overcome by systematic manipulation of experimental conditions such as the flow rate and the surface density of the immobilized antigen. Because of the multivalent nature of ferritin with 12 antiferritin Fab' binding sites per molecule, immobilization of the antigen by amine coupling had little effect on the majority of free binding sites on the molecule. Consequently, the binding data for both ferritin and apoferritin correlated well with an ideal binding model which assumes binding homogeneity. On the other hand, when ferritin was dissociated to its subunit dimer form (containing one Fab' binding site) prior to surface immobilization significant deviation from this model was observed. This nonideal behavior was probably due to heterogeneity of the immobilized ferritin subunit dimer on the sensor surface, resulting from the nonspecific amine coupling procedure.

Alkylation

Glucocorticoid deficient hypoadrenocorticism in dogs: 18 cases (1986-1995).

OBJECTIVE: To characterize naturally developing glucocorticoid deficiency in dogs. DESIGN: Retrospective case series. ANIMALS: 18 dogs with glucocorticoid deficiency defined by an inadequate response to stimulation with adrenocorticotropic hormone (ACTH), a normal Na:K ratio (> 27), and no history of receiving corticosteroids for at least 6 weeks. PROCEDURE: Information including signalment, body weight, clinical signs on admission, historical findings, physical examination findings, results of CBC and serum biochemical analyses, results of ACTH stimulation tests and other ancillary endocrine tests, diagnostic imaging findings, findings from other procedures such as endoscopy and surgery, and information on concurrent diseases, management, and outcome were retrieved from the medical records of dogs with glucocorticoid deficiency treated between 1986 and 1995 at the University of Pennsylvania's School of Veterinary Medicine and 2 dogs from private practices. RESULTS: Most dogs were young (< 7 years) and represented larger breeds (> 20 kg). Clinical signs were nonspecific: lethargy, weight loss, and gastrointestinal disturbances including regurgitation with radiographic evidence of megaesophagus. Hypocholesterolemia, hypoalbuminemia, hypoglycemia, and a mild, nonregenerative anemia were common. Ten of the 18 dogs responded well to glucocorticoid supplementation alone, with only 2 dogs developing electrolyte abnormalities. Four (22%) of the dogs died, with death usually occurring as a result of secondary disease processes rather than hypoadrenocorticism. CLINICAL IMPLICATIONS: An ACTH stimulation test should be considered as part of the diagnostic plan in dogs with signs of weight loss, inappetence, and intermittent vomiting and diarrhea. Glucocorticoid-deficient dogs may not require supplemental mineralocorticoids.

Adrenal Cortex Function Tests

Clinical and clinicopathologic findings in dogs with acute respiratory distress syndrome: 19 cases (1985-1993).

OBJECTIVE: To describe clinical and clinicopathologic findings from dogs with histologic pulmonary lesions consistent with human adult respiratory distress syndrome and to identify potential factors. DESIGN: Retrospective study. ANIMALS: 19 dogs with acute respiratory distress. PROCEDURE: Medical records of dogs were reviewed. Signalment, physical examination and clinicopathologic findings at admission, and thoracic radiographic and necropsy findings were recorded. RESULTS: The most common clinical sign was dyspnea. Respiratory rate ranged from 36 to 140 breaths/min and abnormal breathing patterns were detected. Crackles were auscultated in 7 dogs. Severe diffuse interstitial and alveolar infiltrates were observed on thoracic radiography in 9 dogs shortly after arrival and developed later in 4 dogs. Four dogs were leukopenic and neutropenic. Disseminated intravascular coagulation was diagnosed in 2 dogs, and hypoalbuminemia was found in 8 dogs. Respiratory status deteriorated rapidly in all dogs, and 10 dogs were mechanically ventilated. Death was attributed solely to respiratory failure in 8 dogs. In the other 11 dogs, severe lesions in nonpulmonary organs, sepsis, or both may have contributed to death. The most common associated conditions that may have contributed to acute respiratory failure were microbial pneumonia, sepsis, aspiration pneumonia, and shock, with more than 1 factor found in 11 of 19 dogs. CLINICAL IMPLICATIONS: The index of suspicion for acute respiratory distress syndrome should be high in dogs with bilateral pulmonary infiltrates and acute respiratory distress that rapidly progresses to failure.

Animals

Respiratory function and treatment in dogs with acute respiratory distress syndrome: 19 cases (1985-1993).

OBJECTIVE: To characterize respiratory function and treatment in dogs with findings compatible with those of human adult respiratory distress syndrome (ARDS) and to evaluate the application in dogs of clinical for diagnosis of ARDS. DESIGN: Retrospective review of medical records. ANIMALS: 19 dogs with acute respiratory distress syndrome. RESULTS: Arterial blood pH was 7.30 +/- 0.59 (mean +/- SD). Nine dogs had metabolic acidosis. In nonmechanically ventilated dogs, PaCO2 was 15.0 to 54.9 mm of Hg. Respiratory acidosis developed in 2 mechanically ventilated dogs. Hypoxemia was observed in 4 of 5 dogs breathing room air. In 4 mechanically ventilated dogs, oxygenation was inadequate, despite use of > 60% inspired O2 and positive end-expiratory pressure in 3 dogs. Alveolar-to-arterial oxygen tension gradients were widened in 4 dogs breathing room air and in 6 dogs ventilated with 100% O2. Ten dogs were mechanically ventilated; ventilatory rate was 18 to 60 breaths/min. Tidal volume was 12 +/- 3.8 ml/kg of body weight in 4 dogs, minute ventilation > 400 ml/kg/min in 2 dogs, and peak airway pressures > 25 cm of H2O in 6 dogs. Positive end-expiratory pressure was used in 8 dogs. Pneumothorax was detected in 5 ventilated dogs. Human clinical criteria for diagnosis of ARDS were fulfilled in 7 dogs. Fluid treatment consisted of IV crystalloids and synthetic colloids. Drugs most often administered were antibiotics and loop diuretics. CLINICAL IMPLICATIONS: Human clinical criteria for identification of ARDS may be helpful in diagnosis of acute respiratory distress syndrome in dogs.

Acid-Base Equilibrium

The diagnosis and management of acute liver failure in dogs and cats.

Management of the small animal patient with a presumptive diagnosis of acute liver failure should aim to provide high quality supportive care aimed at the functional derangements that occur. A definitive histopathologic diagnosis should be pursued to allow evaluation of the reversibility of the underlying condition. With the current advances in veterinary critical care, improved medical and technical management should reduce both morbidity and mortality in the patient with potentially reversible liver failure.

Animals

The lipase to amylase ratio in acute pancreatitis.

OBJECTIVES: The ratio of serum lipase to serum amylase has been proposed to distinguish acute episodes of alcoholic from nonalcoholic pancreatitis. We evaluated the efficacy of this test in a community hospital setting. METHODS: Charts of all patients discharged with a diagnosis of acute pancreatitis over 19 months were retrospectively reviewed. Patients were excluded if their creatinine was greater than 3.0 mg/dl, if the amylase and lipase were not measured within 72 h of the onset of symptoms, or if the cause of pancreatitis was not known by the time of discharge. RESULTS: Of the 56 patients, 31 had alcoholic pancreatitis. The lipase to amylase ratio did not differ significantly between patients with alcoholic and nonalcoholic pancreatitis. Median amylase and lipase were significantly higher in nonalcoholic pancreatitis; however, the wide ranges of both meant that neither amylase nor lipase accurately determined the cause of pancreatitis. CONCLUSION: The lipase to amylase ratio does not appear to be sufficiently sensitive or specific to distinguish alcoholic from nonalcoholic acute pancreatitis.

Acute Disease

Use of positive-pressure ventilation in dogs and cats: 41 cases (1990-1992).

Intermittent positive-pressure ventilation (PPV) is an invasive means of respiratory support that is indicated in animals with central and peripheral neuromuscular disease, as well as in those with primary disorders of the lung parenchyma. We reviewed the medical records of 34 dogs and 7 cats treated with PPV. The animals could be allotted to 2 groups; group 1 (21/41) had primary failure of ventilation attributable to neuromuscular disease or airway obstruction, and group 2 (20/41) had primary pulmonary parenchymal disease. Mean inspiratory time was 1.02 +/- 0.2 seconds (range, 0.6 to 1.5 seconds). Mean inspiratory flow was 26.9 +/- 18.5 L/min (range, 7 to 87 L/min), and was positively correlated with body weight (R = 0.57). Mean set respiratory rate was 19.6 +/- 10 breaths/min (range, 5 to 60 breaths/min), with mean tidal volume of 15.5 +/- 6.2 ml/kg of body weight. Positive end-expiratory pressure (PEEP) was required in 14 of 20 dogs in group 2. Mean peak airway pressure in group 1 was 21.6 +/- 6.3 cm of H2O, whereas in group 2 it was 32.9 +/- 12.5 cm of H2O. The higher peak airway pressure in group-2 dogs reflected poor lung compliance and the use of PEEP in dogs with parenchymal lung disease. Mean duration of PPV was 28.2 +/- 29.4 hours (range, 2 to 137 hours). The overall survival rate was 39% (16/41).(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Obstruction

Postoperative complications and prognostic indicators in dogs and cats with septic peritonitis: 23 cases (1989-1992).

Medical records of 21 dogs and 2 cats treated for septic peritonitis were reviewed. Animals were between 1 and 12 years old, (mean, 6.5 years) and weighed between 6 and 51.4 kg (mean, 22.7 kg). Overall, 13 animals survived and were discharged from the hospital. Immediately after surgical correction of the underlying cause of peritonitis, most animals were tachycardic (mean heart rate, 148 beats/min; range, 80 to 204 beats/min), and many were hypotensive (mean arterial pressure, 84.4 mm of Hg; range, 44 to 156 mm of Hg). Hypotension was attributed to sepsis and hypovolemia secondary to extensive loss of fluid into the peritoneal cavity. Survivors did not differ from nonsurvivors with regard to mean arterial pressure immediately after surgery, and in most animals, hypotension could be corrected by IV administration of fluids. Three animals died after failing to respond to fluid treatment, despite concurrent administration of inotropic or pressor agents. Mean rate for crystalloid fluid administration was 12.8 ml/kg of body weight/h (range, 5 to 23.5 ml/kg/h) during the first 24 hours after surgery. Six of 23 animals had low urine output for a short time after surgery, but urine output increased when fluids were administered. Hypoalbuminemia developed in all animals (mean serum albumin concentration, 1.17 g/dl; range, 0.6 to 2.3 g/dl), and peripheral edema developed in 13. Neither lowest mean serum albumin concentration nor fluid administration rate was significantly different between animals that developed peripheral edema and those that did not. Fluid administration rates were significantly higher in nonsurvivors (15 ml/kg/h; range, 5.5 to 23.5 ml/kg/h) than in survivors (11 ml/kg/h; range, 5 to 17.5 ml/kg/h).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Acute vomiting.

Patients commonly present to the emergency clinician for evaluation of acute vomiting. The causes of vomiting range from trivial to life-threatening. The clinician must use the history, physical examination, emergency data-base, and abdominal radiographs to determine the severity of the underlying problem and the extent of the systemic side-effects of vomition. Based on this information, a plan can be devised for optimal emergency management of these patients.

Acute Disease

Chlamydia trachomatis infections in female tertiary students.

Chlamydial infection of the endocervix was identified in 19.8% of 258 University students undergoing pelvic examination in a Student Services Health Clinic. The majority of consultations were for routine Papanicolaou smear. Chlamydial infection was present in 50% (12 of 24) of the women who had clinical evidence of mucopurulent cervicitis.

Adult

Arterial blood gas tensions in healthy aged dogs.

Twenty-four healthy dogs > 8 years old were recruited. In each instance, arterial blood gas tensions were analyzed. The alveolar-to-arterial oxygen gradient (P[A-a]O2) was calculated to assess adequacy of pulmonary gas exchange. Thoracic radiographs were evaluated to ensure lack of visible signs of pulmonary disease and that lung features were similar to those in aged dogs of previous reports. Unlike findings in aged human beings, arterial partial pressure of oxygen (PaO2) was not decreased in this group of aged dogs (mean +/- SD, 102.9 +/- 7.8 mm of Hg). Similarly, P(A-a)O2 also was not increased. The thoracic radiographic findings were consistent with those of previous reports of pulmonary changes in aged dogs. The extent of radiographic abnormalities and the PaO2 were not correlated.

Aging

Static thoracic compliance as a measurement of pulmonary function in dogs.

Thoracic compliance measurements by use of readily available equipment were determined to be practical and safe in dogs. Twenty healthy dogs (age 1 to 16 years, weight 2.3 to 49.5 kg) were anesthesized for routine procedures such as dentistry or neutering. The animals were first hyperventilated to reduce pulmonary atelectasis, to check for leakage at the endotracheal tube cuff, and to induce mild hypocarbia, thus minimizing voluntary respiratory efforts. Total thoracic compliance measurements were calculated as the difference between exhaled volumes at static inspiratory pressures of 15 and 20 cm of H2O, divided by the pressure difference, and expressed as a function of body weight. The procedure was easy, took 5 to 10 minutes, and caused no recognizable ill effects in any of the dogs studied. Mean total thoracic compliance was 42.25 +/- 32 ml/cm of H2O. There was a significant correlation with weight, but no significant relationship was seen between compliance and age, or gender. The mean weight-adjusted total thoracic compliance was 1.85 +/- 0.56 ml/cm of H2O/kg. In studies in a small group of dogs with documented respiratory tract disease, 4 of 7 had a mean compliance greater than 2 SD below the normal range. Thus, this test may become part of the routine workup of any animal being anesthetized for procedures such as bronchoscopy to evaluate respiratory tract disease. Routine monitoring of animals on ventilators could provide early warning of complications such as pneumonia, pleural effusion, or pulmonary edema.

Animals