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Biomedical subjects

Leah A Cohn

Publications and source records attributed to Leah A Cohn.

At least 19 recordsLinked to original sources

Evaluation of a continuous glucose monitoring system for use in veterinary medicine.

BACKGROUND: With the emergence of continuous glucose monitoring systems being used to provide a detailed glucose picture in humans, a commercially available system (CGMS(R), Medtronic Minimed, Northridge, CA) was examined for use in veterinary species. METHODS: Adult, clinically normal horses (n = 7), cats (n = 3), dogs (n = 4), and cows (n = 5) were studied. Cats (n = 4), dogs (n = 5), and one horse with diabetes were included in the study. Several of the normal horses, including the horse with diabetes, and one cow were subjected to an intravenous glucose tolerance test. The CGMS was attached to each animal, and the recorded interstitial glucose concentrations were compared with whole blood glucose concentrations as determined by a point-of-care glucose meter. Events such as insulin administration, feeding, travel, or administration of intravenous glucose were all noted and compared with results from the CGMS. RESULTS: There was a positive correlation between interstitial and whole blood glucose concentrations for all the clinically normal species, those with diabetes mellitus, and those receiving intravenous glucose. Events such as feeding, glucose or insulin administration, and transport to the clinic were noted by the owner or clinician and could be identified on the graph and correlated with time of occurrence. CONCLUSIONS: Our data indicate that the use of the CGMS is valid for use in the species examined. Use of this system alleviated the need for multiple blood samples and the stress associated with obtaining those samples. This system may provide greater monitoring capabilities in patients with diabetes and promote the diagnostic and research potential of serial glucose monitoring in veterinary species.

Animals↗

Cardiopulmonary effects of medetomidine, oxymorphone, or butorphanol in selegiline-treated dogs.

OBJECTIVES: To determine if chronic selegiline HCl administration affects the cardiopulmonary response to medetomidine, oxymorphone, or butorphanol in dogs. STUDY DESIGN: Prospective randomized experimental study. ANIMALS: Twenty-eight adult, random source, hound dogs weighing 21-33 kg. METHODS: Dogs were assigned to the following treatment groups: selegiline + medetomidine (MED; n = 6); placebo + MED (n = 6), selegiline + oxymorphone (OXY; n = 6); placebo + OXY (n = 6); selegiline + butorphanol (BUT; n = 7) or placebo + BUT (n = 6). Nine dogs were treated with two of the three pre-medicants. Dogs were treated with selegiline (1 mg kg(-1) PO, q 24 hours) or placebo for at least 44 days prior to pre-medicant administration. On the day of the experiment, arterial blood for blood gas analysis, blood pressure measurements, ECG, cardiac ultrasound (mM-mode, 2-D, and continuous wave Doppler), and behavioral observations were obtained by blinded observers. An IV injection of MED (750 micro g m(-2)), OXY (0.1 mg kg(-1)) or BUT (0.4 mg kg(-1)) was given. Cardiopulmonary and behavioral data were collected at 1, 2, 5, 15, 30, and 60 minutes after injection. RESULTS: Selegiline did not modify responses to any of the pre-medicant drugs. Medetomidine caused a significant decrease in heart rate (HR), cardiac output (CO), and fractional shortening (FS). Mean arterial pressure (MAP), systemic vascular resistance (SVR), and central venous pressure (CVP) were increased. Level of consciousness and resistance to restraint were both decreased. Oxymorphone did not affect MAP, CO, CVP, or SVR, but RR and PaCO(2) were increased. Level of consciousness and resistance to restraint were decreased. BUT decreased heart rate at 1 and 5 minutes. All other cardiovascular parameters were unchanged. BUT administration was associated with decreased arterial pH and increased PaCO(2). BUT decreased level of consciousness and resistance to restraint. CONCLUSIONS AND CLINICAL RELEVANCE: Although pre-medicants themselves altered cardiopulmonary and behavioral function, selegiline did not affect the response to medetomidine, oxymorphone, or butorphanol in this group of normal dogs.

Animals↗

Evaluation of a continuous glucose monitoring system for use in dogs, cats, and horses.

OBJECTIVE: To evaluate a continuous glucose monitoring system (CGMS) for use in dogs, cats, and horses. DESIGN: Prospective clinical study. Animals-7 horses, 3 cats, and 4 dogs that were clinically normal and 1 horse, 2 cats, and 3 dogs with diabetes mellitus. PROCEDURE: Interstitial glucose concentrations were monitored and recorded every 5 minutes by use of a CGMS. Interstitial glucose concentrations were compared with whole blood glucose concentrations as determined by a point-of-care glucose meter. Interstitial glucose concentrations were also monitored in 2 clinically normal horses after oral and i.v. administration of glucose. RESULTS: There was a positive correlation between interstitial and whole blood glucose concentrations for clinically normal dogs, cats, and horses and those with diabetes mellitus. Events such as feeding, glucose or insulin administration, restraint, and transport to the clinic were recorded by the owner or clinician and could be identified on the graph and associated with time of occurrence. CONCLUSIONS AND CLINICAL RELEVANCE: Our data indicate that use of CGMS is valid for dogs, cats, and horses. This system alleviated the need for multiple blood samples and the stress associated with obtaining those samples. Because hospitalization was not required, information obtained from the CGMS provided a more accurate assessment of the animal's glucose concentrations for an extended period, compared with measurement of blood glucose concentrations. Use of the CGMS will promote the diagnostic and research potential of serial glucose monitoring.

Animals↗

Targeted delivery of antiprotease to the epithelial surface of human tracheal xenografts.

The cystic fibrosis (CF) lung is uniquely susceptible to Pseudomonas aeruginosa, and infection with this organism incites an intense, compartmentalized inflammatory response that leads to chronic airway obstruction and bronchiectasis. Neutrophils migrate into the airway, and released neutrophil elastase contributes to the progression of the lung disease characteristic of CF. We have developed a strategy that permits the delivery of antiproteases to the inaccessible CF airways by targeting the respiratory epithelium via the human polymeric immunoglobulin receptor (hpIgR). A fusion protein consisting of a single-chain Fv directed against secretory component, the extracellular portion of the pIgR, linked to human alpha1-antitrypsin is effectively ferried across human tracheal xenografts and delivers the antiprotease to the apical surface to a much greater extent than occurs by passive diffusion of human alpha1-antitrypsin alone. Targeted antiprotease delivery paralleled hpIgR expression in the respiratory epithelium in vivo and was not increased by escalating dose, so airway penetration was receptor-dependent, not dose-dependent. Thus, this approach provides us with the ability to deliver therapeutics, like antiproteases, specifically to the lumenal surface of the respiratory epithelium, within the airway surface fluid, where it will be in highest concentration at this site.

Animals↗

Ehrlichiosis and related infections.

Ehrlichiosis is a term that has been used to describe infection with any of a number of related intracellular, vector-borne pathogens. A recent reclassification has resulted in the transfer of several species previously known as Ehrlichia to the genus Anaplasma or Neorickettsia. Ehrlichia and Anaplasma are transmitted largely through the bite of infected ticks, while vectors for Neorickettsia include trematodes and the intermediate hosts (i.e., fish, snails, and insects) involved in the trematode life cycle. Dogs (and cats) are susceptible to infection with several of these pathogens, and veterinarians should be aware of the similarities and differences between E canis and related infections. Pets with suggestive clinical signs and laboratory abnormalities may be started on doxycycline pending specific diagnostic testing. The veterinarian practicing in endemic areas must understand the implications and limitations of serologic and molecular testing to confirm a diagnosis. For animals in endemic areas, prevention of exposure to vectors can lessen the risk of disease for pets and might lessen the potential for animals to become carriers of disease for their human companions.

Anaplasma↗

Haemophilus influenzae Rd KW20 has virulence properties.

Haemophilus influenzae is a human-adapted commensal and pathogen that can cause mucosal infections such as sinusitis, otitis media and bronchitis. Certain strains also cause bacteraemia and meningitis. Clinical isolates are genetically heterogeneous and are often recalcitrant to standard genetic manipulation. H. influenzae strain Rd KW20 has traditionally been considered avirulent, since it does not survive in the bloodstream of animals, is readily killed by normal adult human sera and cannot colonize the nasopharynx of infant rats. The purpose of this study was to determine whether Rd KW20 could be used in certain infection models. It is shown here that strain Rd KW20 can invade certain human epithelial cell lines grown either as monolayers or as differentiated epithelium at the air-liquid interface. In addition, Rd KW20 can invade a monolayer of immortalized human brain microvascular endothelial cells. Finally, this strain can replicate and survive in human bronchial xenografts for up to 3 weeks. The complete genomic sequence of Rd KW20 is available and it is readily amenable to genetic manipulation. These properties and the results reported here indicate that this strain is a viable alternative to the use of clinical isolates for the investigation of H. influenzae virulence.

Animals↗

Trends in fluoroquinolone resistance of bacteria isolated from canine urinary tracts.

Fluoroquinolone (FQ) antimicrobial agents are used extensively in human and veterinary medicine. Widespread use of any antimicrobial agent can apply selective pressure on populations of bacteria, which may result in an increase in the prevalence of antimicrobial-resistant isolates. Antimicrobial-susceptibility data on bacteria isolated from the canine urinary tract by the University of Missouri-Columbia Veterinary Medical Diagnostic Laboratory, Columbia, MO, were used to determine whether there has been an increase in the prevalence of FQ-resistant bacteria over time. Between January 1992 and December 2001, minimum inhibitory concentrations of either ciprofloxacin (1992-1998) or enrofloxacin (1998-2001) were determined for 1,478 bacterial isolates from the canine urinary tract. The predominant bacterial species isolated were Escherichia coli (547 isolates), Proteus mirabilis (156), and Staphylococcus intermedius (147). In all, there were 13 bacterial species with more than 25 isolates each. A significant increase in the overall proportion of resistant bacterial isolates was documented from 1992 to 2001 (Cochran-Armitage test for trend, P < 0.0001). The same increase in resistant isolates was documented when either ciprofloxacin or enrofloxacin was analyzed separately (P < 0.0001 and P < 0.0002, respectively). No difference was detected in rates of bacterial FQ resistance with regard to the sex of the dog from which the bacteria were isolated. The frequency with which some bacterial species were isolated differed with the sex of the infected dog. Proteus mirabilis was found more often in females (P < 0.0001), whereas beta hemolytic Streptococcus spp., were found more often in males (P = 0.0003). Although the overall efficacy of FQ antimicrobials remained high with greater than 80% of isolates being susceptible, the data demonstrated an increase in the proportion of resistant bacteria isolated from the urinary tract of the dog.

Animals↗

Acylation of the lipooligosaccharide of Haemophilus influenzae and colonization: an htrB mutation diminishes the colonization of human airway epithelial cells.

Haemophilus influenzae is a commensal and opportunistic pathogen of the human airways. A number of surface molecules contribute to colonization of the airways by H. influenzae, such as adhesins, including structures found in the lipooligosaccharide (LOS). A human bronchiolar xenograft model was employed to investigate the host-bacterial interactions involved in the colonization of the airway by H. influenzae. Differential display was used to identify H. influenzae mRNA that reflect genes which were preferentially expressed in the xenograft compared to growth. Eleven mRNA fragments had consistent increased expression when the bacteria grew in xenografts. On sequencing these fragments, eight open reading frames were identified. Three of these had no match in the NCBI or the TIGR database, while an additional three were homologous to genes involved in heme or iron acquisition and utilization: two of the mRNAs encoded proteins homologous to enzymes involved in LOS biosynthesis: a heptosyl transferase (rfaF) involved in the synthesis of the LOS core and a ketodeoxyoctonate phosphate-dependent acyltransferase (htrB) that performs one of the late acylation reactions in lipid A synthesis. Inoculation of human bronchiolar xenografts revealed a significant reduction in colonization capacity by htrB mutants. In vitro, htrB mutants elicited lesser degrees of cytoskeletal rearrangement and less stimulation of host cell signaling with 16HBE14o(-) cells and decreased intracellular survival. These results implicate acylation of H. influenzae lipid A as playing a key role in the organisms' colonization of the normal airway.

Acylation↗

Effects of selegiline, phenylpropanolamine, or a combination of both on physiologic and behavioral variables in healthy dogs.

OBJECTIVE: To determine effects of selegiline hydrochloride, phenylpropanolamine (PPA), or a combination of both on physiologic and behavioral variables in dogs. ANIMALS: 40 adult hound-type dogs. PROCEDURE: Dogs were assigned to 4 groups. One group received selegiline (1 mg/kg, PO, q 24 h) and PPA (1.1 mg/kg, PO, q 8 h), a second group received selegiline alone, a third group received PPA alone, and a fourth group received neither drug. Dogs were observed 3 times/d throughout the 30-day study (daily during the first week, on alternate days during the next 2 weeks, and again daily during the final week). Observers recorded rectal temperature, pulse, respiratory rate, oscillometric blood pressure, and lead-II ECG and assessed 4 behaviors, using an analogue scale. Variables were compared among treatment groups by use of a 2-factor ANOVA with data categorized into three 10-day treatment periods. A similar comparison was made among treatment groups with data categorized by time of observation (morning, afternoon, or evening) for all study days. RESULTS: Variables did not differ among groups at study initiation. Pulse rate was the only variable that differed significantly among treatment groups during the study. During the first 10 days of treatment, dogs receiving PPA had a lower pulse rate than dogs that did not. Although signs of illness were apparent in a few dogs, illness did not appear to be related to treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Adverse effects were not detected after administration of selegiline, PPA, or a combination of the drugs in healthy dogs.

Animals↗

The effects of exercise on urinary albumin excretion in dogs.

Persistent microalbuminuria has been shown to be an indicator of glomerular damage associated with early progressive renal disease in people and dogs. In people, transient or reversible microalbuminuria has been shown to occur with exercise. A semi-quantitative test to measure microalbuminuria in the dog recently has become available. The purpose of this study was to determine if mild-to-moderate exercise induced microalbuminuria in the dog. Twenty-six dogs were included in the study after undergoing tests to rule out hyperglycemia, urinary tract infection, azotemia, and a urine protein:creatinine ratio >1. Exercise consisted of 20 minutes of flat treadmill running. Urine samples were collected on 2 separate days before exercise, the morning of exercise, 3 hours postexercise, 7-9 hours postexercise, and each of the 2 mornings after exercise. For 24 of 26 dogs, this procedure was repeated after a minimum 7-day interval between exercise sessions. The canine E.R.D. (early renal disease)-Screen Urine Test (E.R.D.-Screen test) was used to determine semiquantitative urine albumin concentrations. Microalbuminuria-positive samples, as determined by the E.R.D.-Screen test, were further analyzed to determine quantitative albumin concentrations. Four (15%) dogs were microalbuminuria positive. In each of these dogs, microalbuminuria was present both before and after exercise with no quantitative increase in urine albumin concentration postexercise. Twenty-two (85%) dogs were microalbuminuria negative throughout the study and did not develop microalbuminuria at any time after exercise. On a 95% confidence interval, the proportion of dogs that might be expected to develop microalbuminuria after exercise is between 0 and 15%.

Albuminuria↗

Identification and characterization of an idiopathic pulmonary fibrosis-like condition in cats.

Interstitial lung diseases are a heterogeneous group of disorders with a variety of causes. In veterinary medicine, such lung diseases with a prominent fibrotic component of unknown etiology are often called idiopathic pulmonary fibrosis (IPF). In human medicine, this term is reserved for a distinct disease entity with specific histologic findings labeled as usual interstitial pneumonia (UIP). We identified 23 cats displaying histologic criteria of UIP The purpose of this retrospective study is to describe the presentation and response to therapy of these cats to better define this disease entity. All but 2 cats were middle aged to older (median 8.7 years), with no apparent sex or breed predisposition. Complaints included respiratory distress (n = 18) and cough (13). Duration of signs was less than 6 months in 17 cats. Physical-examination abnormalities included tachypnea, inspiratory or mixed inspiratory and expiratory effort, and adventitial lung sounds. No consistent hematologic or biochemical abnormalities, parasites, or positive serologic results for feline retroviruses, heartworms, or toxoplasmosis were present. Radiographic changes included dense patchy or diffuse interstitial, bronchiolar, and alveolar infiltrates. Analysis of bronchial lavage fluid revealed mild neutrophilic inflammation (n = 6) with no consistent pathogen growth. Clinical condition of 5 cats worsened after lavage. Coincident pulmonary neoplasia was identified in 6 cats. Response to therapy (corticosteroids, antibiotics, bronchodilators, and diuretics) was poor, and most cats died within days to months. Cats with histologic changes compatible with UIP had signs that mimicked many of the clinical findings of human IPF, and treatment response was similarly unrewarding.

Animals↗

Acquired portosystemic shunting in two cats.

Acquired portosystemic shunts (PSS) are a clinical entity distinct from congenital PSS. Their apparent incidence in cats is low, which may reflect the rarity of predisposing hepatic parenchymal disease, such as cirrhosis, in this species. Two cats with acquired PSS associated with primary hepatobiliary disease are described. Relevant findings in acquired PSS are discussed, as are potential reasons for the apparently low incidence in the cat.

Animals↗