Hospital-acquired Anemia in Critically Ill Dogs and Cats: A Multi-Institutional Study.

BACKGROUND: Hospital-acquired anemia is commonly described in people but limited information currently is available regarding its prevalence in animals. HYPOTHESIS/OBJECTIVES: Assess the prevalence of hospital-acquired anemia in hospitalized critically ill dogs and cats, and examine its relationship with phlebotomy practices, transfusion administration, and survival to discharge. ANIMALS: Eight hundred and fifty-one client-owned animals (688 dogs and 163 cats). METHODS: A multicenter, observational study was conducted in which packed cell volume (PCV) was recorded at the time of admission and on subsequent hospitalization days. Signalment, number of blood samples obtained, underlying disease, whether or not blood products were administered, duration of hospitalization, and survival to discharge were recorded. RESULTS: Admission anemia prevalence was 32%, with overall prevalence during the hospitalization period of 56%. The last recorded PCV was significantly lower than the admission PCV for both dogs (admission PCV, 42% [range, 6-67%]; last recorded PCV, 34% [range, 4-64%], P < .0001) and cats (admission PCV, 31% [range, 6-55%]; last recorded PCV, 26% [range, 10-46%], P < .0001). Patients that developed anemia had significantly more blood samples obtained (nonanemic, 5 blood samples [range, 2-54]; anemic, 7 blood samples [range, 2-49], P < .0001). Hospitalized cats were significantly more likely to develop anemia compared to dogs (P < .0001), but anemic dogs were significantly less likely to survive to discharge (P = .0001). Surgical patients were at higher risk of developing hospital-acquired anemia compared to medical patients (OR, 0.63; 95% CI, 0.4-0.9; P = .01). CONCLUSIONS AND CLINICAL RELEVANCE: Hospital-acquired anemia occurred frequently, especially in surgical patients. Additional studies focused on the direct effect of phlebotomy practices on the likelihood of anemia development in hospitalized animals are warranted.

Electroencephalogram of Healthy Horses During Inhaled Anesthesia.

BACKGROUND: Previous study of the diagnostic validity of electroencephalography (EEG) to detect abnormalities in equine cerebral cortical function relied on the administration of various drugs for sedation, induction, and maintenance of general anesthesia but used identical criteria to interpret recordings. OBJECTIVES: To determine the effects of 2 inhalation anesthetics on the EEG of healthy horses. ANIMALS: Six healthy horses. METHODS: Prospective study. After the sole administration of one of either isoflurane or halothane at 1.2, 1.4, and 1.6 times the minimum alveolar concentration, EEG was recorded during controlled ventilation, spontaneous ventilation, and nerve stimulation. RESULTS: Burst suppression was observed with isoflurane, along with EEG events that resembled epileptiform discharges. Halothane results were variable between horses, with epileptiform-like discharges and bursts of theta, alpha, and beta recorded intermittently. One horse died and 2 were euthanized as the result of anesthesia-related complications. CONCLUSIONS AND CLINICAL IMPORTANCE: The results of this study indicate that the effects of halothane and isoflurane on EEG activity in the normal horse can be quite variable, even when used in the absence of other drugs. It is recommended that equine EEG be performed without the use of these inhalation anesthetics and that general anesthesia be induced and maintained by other contemporary means.

Qualitative and Quantitative Characteristics of the Electroencephalogram in Normal Horses during Administration of Inhaled Anesthesia.

BACKGROUND: The effects of anesthesia on the equine electroencephalogram (EEG) after administration of various drugs for sedation, induction, and maintenance are known, but not that the effect of inhaled anesthetics alone for EEG recording. OBJECTIVE: To determine the effects of isoflurane and halothane, administered as single agents at multiple levels, on the EEG and quantitative EEG (qEEG) of normal horses. ANIMALS: Six healthy horses. METHODS: Prospective study. Digital EEG with video and quantitative EEG (qEEG) were recorded after the administration of one of the 2 anesthetics, isoflurane or halothane, at 3 alveolar doses (1.2, 1.4 and 1.6 MAC). Segments of EEG during controlled ventilation (CV), spontaneous ventilation (SV), and with peroneal nerve stimulation (ST) at each MAC multiple for each anesthetic were selected, analyzed, and compared. Multiple non-EEG measurements were also recorded. RESULTS: Specific raw EEG findings were indicative of changes in the depth of anesthesia. However, there was considerable variability in EEG between horses at identical MAC multiples/conditions and within individual horses over segments of a given epoch. Statistical significance for qEEG variables differed between anesthetics with bispectral index (BIS) CV MAC and 95% spectral edge frequency (SEF95) SV MAC differences in isoflurane only and median frequency (MED) differences in SV MAC with halothane only. CONCLUSIONS AND CLINICAL IMPORTANCE: Unprocessed EEG features (background and transients) appear to be beneficial for monitoring the depth of a particular anesthetic, but offer little advantage over the use of changes in mean arterial pressure for this purpose.

Therapeutic plasma concentrations of epsilon aminocaproic acid and tranexamic acid in horses.

BACKGROUND: Antifibrinolytic drugs such as epsilon aminocaproic acid (EACA) and tranexamic acid (TEA) are used to treat various bleeding disorders in horses. Although horses are hypofibrinolytic compared to humans, dosing schemes have been derived from pharmacokinetic studies targeting plasma concentrations in humans. HYPOTHESIS/OBJECTIVES: We hypothesized therapeutic plasma concentrations of antifibrinolytic drugs in horses would be significantly lower than in humans. Our objective was to use thromboleastography (TEG) and an in vitro model of hyperfibrinolysis to predict therapeutic concentrations of EACA and TEA in horses and humans. ANIMALS: Citrated plasma collected from 24 random source clinically healthy research horses. Commercial pooled human citrated plasma with normal coagulation parameters was purchased. METHODS: Minimum tissue plasminogen activator (tPA) concentration to induce complete fibrinolysis within 10 minutes was determined using serial dilutions of tPA in equine plasma. Results used to create an in vitro hyperfibrinolysis model with equine and human citrated plasma, and the minimum concentrations of EACA and TEA required to completely inhibit fibrinolysis for 30 minutes (estimated therapeutic concentrations) determined using serial dilutions of the drugs. RESULTS: Estimated therapeutic concentrations of EACA and TEA were significantly lower in horses (5.82; 95% CI 3.77-7.86 µg/mL and 0.512; 95% CI 0.277-0.748 µg/mL) than in humans (113.2; 95% CI 95.8-130.6 µg/mL and 11.4; 95% CI 8.62-14.1 µg/mL). CONCLUSIONS AND CLINICAL IMPORTANCE: Current dosing schemes for EACA and TEA in horses may be as much as 20× higher than necessary, potentially increasing cost of treatment and risk of adverse effects.

Qualitative and quantitative characteristics of the electroencephalogram in normal horses after sedation.

BACKGROUND: The administration of certain sedatives has been shown to promote sleep in humans. Related agents induce sleep-like behavior when administered to horses. Interpretation of electroencephalograms (EEGs) obtained from sedated horses should take into account background activity, presence of sleep-related EEG events, and the animal's behavior. HYPOTHESIS: Sedatives induce states of vigilance that are indistinguishable on EEGs from those that occur naturally. ANIMALS: Six healthy horses. METHODS: Digital EEG with video was recorded after administration of 1 of 4 sedatives (acepromazine, butorphanol, xylazine, or detomidine). Serum drug concentrations were measured. Recordings were reviewed, states were identified, and representative EEG samples were analysed. These data were compared with data previously obtained during a study of natural sleep. RESULTS: Butorphanol was associated with brief episodes resembling slow wave sleep in 1 horse. Acepromazine led to SWS in 3 horses, including 1 that also exhibited rapid eye movement sleep. Periods of SWS were observed in all horses afer xylazine or detomidine administration. Normal sleep-related EEG events and heart block, occurred in association with SWS regardless of which sedative was used. Spectral data varied primarily by state, but some differences were observed between sedative and natural data. CONCLUSIONS AND CLINICAL IMPORTANCE: Qualitatively, EEG findings appeared identical whether sedation-induced or naturally occurring. The startle response and heart block associated with some sedatives may be related to sleep. Alpha(2) agonists can be used to obtain high quality EEGs in horses, but acepromazine does not promote a relaxed state in all animals.

Qualitative and quantitative characteristics of the electroencephalogram in normal horses during spontaneous drowsiness and sleep.

BACKGROUND: The influence of sleep on the equine electroencephalogram (EEG) has not been well documented. HYPOTHESIS: The objectives were to develop a noninvasive method of electrode placement for recording the EEG in horses and to establish normal EEG parameters for the various states of vigilance. Findings are compared with previously published reports on equine sleep based on electrocorticography (ECoG). ANIMALS: Five neurologically normal horses. METHODS: Overnight EEGs were recorded digitally in association with simultaneous videotaping of the horses' behavior. Data were analyzed by visual inspection, states of vigilance were identified, and representative segments were quantitatively processed. Transient EEG events were examined. RESULTS: Slow wave sleep (SWS) was significantly different (P < .05) in frequency and power from drowsiness and rapid eye movement (REM) sleep. Second-degree heart block was associated with SWS as were transient events commonly recognized in EEGs of humans. Drowsiness and REM sleep were similar. In both, background activity was low-amplitude beta activity admixed with prominent activity of approximately 4 Hz. Standing REM sleep was associated with numerous partial collapses in 1 horse. CONCLUSIONS AND CLINICAL IMPORTANCE: Normative data for several states were described and probable benign variants identified. This information will serve as control data for sedative and anesthetic studies in this species. The sleep patterns observed during this study are those of horses removed from their usual surroundings, and thus may represent those encountered in a clinical environment.

Metastatic adenocarcinoma arising from a small bowel duplication cyst.

A case report of adenocarcinoma arising from a small bowel mesenteric cyst is presented. A discussion and review of the relevant literature then follows.

Beta(3)-adrenoceptor agonist-induced increases in lipolysis, metabolic rate, facial flushing, and reflex tachycardia in anesthetized rhesus monkeys.

The effects of two beta(3)-adrenergic receptor agonists, (R)-4-[4-(3-cyclopentylpropyl)-4,5-dihydro-5-oxo-1H-tetrazol-1-yl]-N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethyl]amino]ethyl]phenyl]benzenesulfonamide and (R)-N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)- ethyl]amino]ethyl]phenyl]-1-(4-octylthiazol-2-yl)-5-indolinesulfonamide, on indices of metabolic and cardiovascular function were studied in anesthetized rhesus monkeys. Both compounds are potent and specific agonists at human and rhesus beta(3)-adrenergic receptors. Intravenous administration of either compound produced dose-dependent lipolysis, increase in metabolic rate, peripheral vasodilatation, and tachycardia with no effects on mean arterial pressure. The increase in heart rate in response to either compound was biphasic with an initial rapid component coincident with the evoked peripheral vasodilatation and a second more slowly developing phase contemporaneous with the evoked increase in metabolic rate. Because both compounds exhibited weak binding to and activation of rhesus beta(1)-adrenergic receptors in vitro, it was hypothesized that the increase in heart rate may be reflexogenic in origin and proximally mediated via release of endogenous norepinephrine acting at cardiac beta(1)-adrenergic receptors. This hypothesis was confirmed by determining that beta(3)-adrenergic receptor agonist-evoked tachycardia was attenuated in the presence of propranolol and in ganglion-blocked animals, under which conditions there was no reduction in the evoked vasodilatation, lipolysis, or increase in metabolic rate. It is not certain whether the beta(3)-adrenergic receptor-evoked vasodilatation is a direct effect of compounds at beta(3)-adrenergic receptors in the peripheral vasculature or is secondary to the release or generation of an endogenous vasodilator. Peripheral vasodilatation in response to beta(3)-adrenergic receptor agonist administration was not attenuated in animals administered mepyramine, indomethacin, or calcitonin gene-related peptide(8-37). These findings are consistent with a direct vasodilator effect of beta(3)-adrenergic receptor agonists.

Sensory gating in chronic posttraumatic stress disorder: reduced auditory P50 suppression in combat veterans.

BACKGROUND: Posttraumatic stress disorder (PTSD) may be associated with a general impairment of cognitive function that extends beyond the processing of trauma-specific stimuli. Suppression of the auditory P50 response to repeated stimuli occurs in normal subjects and reflects the central nervous system's ability to screen out repetitive stimuli, a phenomenon referred to as sensory gating. This study examines P50 sensory gating to nonstartle auditory stimuli in PTSD subjects and normal controls. METHODS: P50 generation and gating were studied using a conditioning/testing paradigm in 15 male subjects with PTSD and 12 male controls. P50 test/conditioning (T/C) ratios were estimated using the Singular Value Decomposition method. RESULTS: The amplitude of the P50 response to the conditioning stimulus did not differ in subjects with PTSD compared to normal controls. The P50 T/C ratio is increased in PTSD subjects (mean = .408, SD = .275) as compared to the controls (mean = .213, SD = .126, two tailed t, p = .024). CONCLUSIONS: This study provides evidence that PTSD is associated with impaired gating to nonstartle trauma-neutral auditory stimuli.

Intra-hemispheric alpha coherence decreases with increasing cognitive impairment in HIV patients.

Inter-hemispheric and intra-hemispheric canonical coherences in the alpha range between EEG signals collected from frontal and posterior groups of electrodes were estimated for 38 HIV positive subjects and 23 uninfected controls. Neuropsychological testing was used to categorize the degree of cognitive impairment evident in each of the subjects. A linear regression analysis provided evidence that intra-hemispheric coherence decreased with increasing cognitive impairment in impaired HIV+ subjects, as measured by a Global Impairment Score (GIS). There was no evidence that cognitively unimpaired HIV+ subjects differed in coherence when compared to uninfected control subjects. Severely impaired HIV+ subjects showed significantly decreased coherence compared to uninfected controls. These data contradict previous work demonstrating increased intra-hemispheric and inter-hemispheric alpha coherence in impaired HIV subjects. In addition, they provide evidence that intra-hemispheric (and possibly inter-hemispheric) disconnection is associated with cognitive impairment in HIV.

Improved method for computation of potentials in a realistic head shape model.

The Lead Field Analysis (LFA) algorithm, a new computational technique for the calculation of potentials on the surface of a realistic head shaped volume conductor model based on the Boundary Element Method and the Reciprocity Theorem, is presented. The new algorithm, in comparison to the Standard Boundary Element Method, offers improved computational efficiency and lower storage requirements. It also yields more accurate surface potential results in the face of varying dipole source locations for a head shape Boundary Element model with a given number of nodes. Additionally, the algorithm results in quasi-analytic expressions of the derivatives of the surface potential with respect to the location of the sources, allowing the use of optimization techniques with better convergence properties. A set of simulations demonstrating the increased robustness of the LFA Algorithm in the face of varying dipole source parameters is also described.

Phorbol esters induce death in MCF-7 breast cancer cells with altered expression of protein kinase C isoforms. Role for p53-independent induction of gadd-45 in initiating death.

Protein kinase C (PKC) modulates growth, differentiation and apoptosis in a cell-specific fashion. Overexpression of PKC-alpha in MCF-7 breast cancer cells (MCF-7-PKC-alpha cell) leads to expression of a more transformed phenotype. The response of MCF-7 and MCF-7-PKC-alpha cells to phorbol esters (TPA) was examined. TPA-treated MCF-7 cells demonstrated a modest cytostatic response associated with a G1 arrest that was accompanied by Cip1 expression and retinoblastoma hypophosphorylation. While p53 was detected in MCF-7 cells, evidence for TPA-induced stimulation of p53 transcriptional activity was not evident. In contrast, TPA treatment induced death of MCF-7-PKC-alpha cells. Bryostatin 1, another PKC activator, exerted modest cytostatic effects on MCF-7 cells while producing a cytotoxic response at low doses in MCF-7-PKC-alpha cells that waned at higher concentrations. TPA-treated MCF-7-PKC-alpha cells accumulated in G2/M, did not express p53, displayed decreased Cip1 expression, and demonstrated a reduction in retinoblastoma hypophosphorylation. TPA-treated MCF-7-PKC-alpha cells expressed gadd-45 which occurred before the onset of apoptosis. Thus, alterations in the PKC pathway can modulate the decision of a breast cancer cell to undergo death or differentiation. In addition, these data show that PKC activation can induce expression of gadd45 in a p53-independent fashion.

Incidence of acute care complications in vertebral column fracture patients with and without spinal cord injury.

STUDY DESIGN: This study retrospectively analyzed vertebral column fractures in trauma patients during a 2-year period. Data from a multicenter trauma registry were used. OBJECTIVES: The purpose of this study was to ascertain and describe the initial in-hospital morbidity and mortality rates for patients with vertebral column fractures with and without spinal cord injury. SUMMARY OF BACKGROUND DATA: Patients with vertebral fractures and associated spinal cord injuries experience more medical complications than those without spinal cord injuries. However, the precise incidence and relative risk of complications during acute care hospitalization for these two groups are not well documented. METHODS: Vertebral column fractures in 419 adolescent and adult trauma patients hospitalized during a 2-year period were retrospectively analyzed using data from a multicenter trauma registry. RESULTS: Of the 419 patients, 104 (24.8%) had an associated spinal cord injury. More than half of the spinal cord injury patients (52.9%) and 20.6% of those without spinal cord injury had one or more complications during their hospitalization. Complications resulted in an average of 33.1 extra hospital days, which extrapolates nationally into 1.5 million additional days annually. The four complications differing most significantly in incidence between the spinal cord injury group and the non-spinal cord injury group were: urinary tract infections (24.0% vs. 8.6%), respiratory (23.1% vs. 8.6%), cardiac (11.5% vs. 3.2%), and decubitus ulcer (7.7% vs. 1.0%). Pneumonia, although not statistically different, was high in both groups (13.5% vs. 7.3%). CONCLUSIONS: The incidence of the 25 types of medical complications reported here provides specific and relevant information to assist health professionals in treating patients during their acute care. We estimate that complications during initial hospitalization add $1.5 billion annually to the cost of caring for patients with vertebral fractures in the United States.

MCF-7 breast cancer cells transfected with protein kinase C-alpha exhibit altered expression of other protein kinase C isoforms and display a more aggressive neoplastic phenotype.

Increased protein kinase C (PKC) activity in malignant breast tissue and positive correlations between PKC activity and expression of a more aggressive phenotype in breast cancer cell lines suggest a role for this signal transduction pathway in the pathogenesis and/or progression of breast cancer. To examine the role of PKC in the progression of breast cancer, human MCF-7 breast cancer cells were transfected with PKC-alpha, and a group of heterogenous cells stably overexpressing PKC-alpha were isolated (MCF-7-PKC-alpha). MCF-7-PKC-alpha cells expressed fivefold higher levels of PKC-alpha as compared to parental or vector-transfected MCF-7 cells. MCF-7-PKC-alpha cells also displayed a substantial increase in endogenous expression of PKC-beta and decreases in expression of the novel delta- and eta-PKC isoforms. MCF-7-PKC-alpha cells displayed an enhanced proliferative rate, anchorage-independent growth, dramatic morphologic alterations including loss of an epithelioid appearance, and increased tumorigenicity in nude mice. MCF-7-PKC-alpha cells exhibited a significant reduction in estrogen receptor expression and decreases in estrogen-dependent gene expression. These findings suggest that the PKC pathway may modulate progression of breast cancer to a more aggressive neoplastic process.

Management of multisite occupational health services. A hospital/private clinic perspective: changing trends for the 1990s.

A strong regional program can be successful in either a single location or at multiple locations, but it cannot function properly if it is not well organized and staffed properly to deliver services. Extremely important elements to the success of an occupational health clinic that serves a wide geographical region are client retention, a strong information system to manage programs for multiple employers, and cutting-edge leadership that stays in the forefront and educates the business community on emerging issues in occupational health and safety.

Age-dependent expression of protein kinase C isoforms in rat islets.

The appearance of the biphasic insulin secretory response several days after birth suggests that maturation of a critical step in stimulus-secretion coupling occurs during the early neonatal period. To clarify the role of protein kinase C (PKC) during this time, we examined the pancreatic islets of adult, 3-day neonatal, and 19-day fetal rats for the presence of different PKC isoenzymes. Western-blot analysis of islet extracts showed the presence of PKC isoforms in both adult and neonatal tissues. Immunocytochemistry of adult islets revealed a differential expression in islet cell types. PKC-alpha was found only in beta-cells, PKC-gamma in alpha-cells, and PKC-epsilon in delta-cells and vascular walls. Immunoreactivity for PKC-beta was not detected in any cell type. All three isoenzymes were also present in neonatal islets; however, in contrast to adult tissue, immunoreactivity for either PKC-alpha or PKC-gamma was present in relatively few cells. There was no apparent immunoreactivity for PKC-alpha or PKC-gamma in fetal islets, although these tissues contained strong staining for insulin and glucagon. These data show that three of the PKC isoforms are restricted to a particular islet cell type, where they may play a unique role in the secretion of a specific hormone. Moreover, our results demonstrate that these enzymes, especially PKC-alpha, appear during the early neonatal period. This age-dependent expression may be linked to the development of the biphasic insulin release response.

Factorial designs for crossover clinical trials.

When measuring the joint effect of two factors it is advantageous to use a factorial design. If the application is suitable, efficiency may be further improved by using a crossover design. This paper presents a flexible method for amalgamating these two devices. Designs are constructed from smaller designs, known as bricks, generated cyclically from tabulated initial sequences. The bricks have known efficiencies for estimation of direct treatment main effects and interactions; the efficiencies can be simply combined to approximate the efficiencies of the whole design. This allows the user to build a design that is tailored to the particular objectives of the experiment. Three and four periods, and two factors with up to four levels are considered.

Effects of combined secretagogues and extracellular calcium on neonatal insulin release.

The insulin response of 3-day old neonatal rat islets was evaluated following a 1 h incubation with glucose alone and in the presence of 30 nM sulfated cholecystokinin octapeptide (CCK) and/or 20 microM carbachol (CCh). Insulin secretion was found to be incrementally increased from the lowest glucose concentration and enhanced several fold in the presence of CCK and/or CCh. In combination, CCK and CCh increased glucose-stimulated insulin secretion by an amount equivalent to the sum of their individual increases. The presence of either CCK alone or CCK plus CCh increased phosphoinositide hydrolysis by the same relative amount that they increased insulin secretion when compared to 8.3 mM glucose. Glucose-stimulated insulin secretion was totally inhibited when calcium was omitted from the incubation buffer; this effect was partially negated by CCK alone and more so by CCK combined with CCh. Insulin secretion in response to 8.3 mM glucose alone was unchanged when calcium in the incubation buffer was increased from 1 to 5 mM; however, the insulin response to 16.7 mM glucose alone and 8.3 mM glucose in the presence of CCK and/or CCh was increased under this condition. Thus, we have shown that, even at 3 days postpartum, insulin secretion from isolated islets is a complex response capable of being molded by several secretagogues at once and ultimately determined by interplay of different signaling systems activated.