A randomized controlled clinical trial of prazosin for alcohol use disorder in active duty soldiers: Predictive effects of elevated cardiovascular parameters.

BACKGROUND: Excessive noradrenergic signaling contributes to aversive symptoms of alcohol withdrawal that interfere with abstinence or reductions in harmful use. METHODS: To address this aspect of alcohol use disorder, 102 active-duty soldiers participating in command-mandated Army outpatient alcohol treatment were randomized to also receive the brain-penetrant alpha-1 adrenergic receptor antagonist prazosin or placebo for 13 weeks. Primary outcomes were scores on the Penn Alcohol Craving Scale (PACS), standard drink units (SDUs) per day averaged over each week, % days of any drinking per week, and % days of heavy drinking per week. RESULTS: PACS declines did not differ significantly between the prazosin and placebo groups in the overall sample. In the subgroup with comorbid PTSD (n = 48), PACS declines were significantly greater in the prazosin than in the placebo condition (p < 0.05). Baseline alcohol consumption was markedly reduced by the pre-randomization outpatient alcohol treatment program, but the addition of prazosin treatment produced a greater slope of decline in SDUs per day compared to placebo (p = 0.01). Preplanned subgroup analyses were performed in soldiers with elevated baseline cardiovascular measures consistent with increased noradrenergic signaling. In soldiers with elevated standing heart rate (n = 15), prazosin reduced SDUs per day (p = 0.01), % days drinking (p = 0.03), and % days heavy drinking (p = 0.001) relative to placebo. In soldiers with elevated standing systolic blood pressure (n = 27), prazosin reduced SDUs per day (p = 0.04) and tended to reduce % days drinking (p = 0.056). Prazosin also reduced depressive symptoms and the incidence of emergent depressed mood more than placebo (p = 0.05 and p = 0.01, respectively). During the final 4 weeks of prazosin vs. placebo treatment that followed completion of Army outpatient AUD treatment, alcohol consumption in soldiers with elevated baseline cardiovascular measures increased in those receiving placebo but remained suppressed in those receiving prazosin. CONCLUSIONS: These results extend reports that higher pretreatment cardiovascular measures predict beneficial effects of prazosin, which may be useful for relapse prevention in patients with AUD.

Intraosseous maxillary hemangioma in an immature Bassett Hound.

A 6-month-old Bassett Hound dog presented for evaluation of recurrent oral bleeding and a right maxillary swelling. Oral examination revealed right maxillary enlargement extending from the level of the right maxillary canine tooth to the area of the second and third premolar teeth. A discolored persistent right maxillary deciduous canine tooth and gingival inflammation was noted. Biopsies taken at the time of extraction of the persistent deciduous canine tooth resulted in significant hemorrhage and a biopsy report of reactive bone. The right maxillary enlargement did not resolve following the extraction procedure and empirical antimicrobial therapy. The owner elected euthanasia and post-mortem evaluation. Histopathologic assessment provided a diagnosis of maxillary hemangioma.

Clinical, ultrasonographic, and laboratory findings associated with gallbladder disease and rupture in dogs: 45 cases (1997-2007).

OBJECTIVE: To identify clinical, laboratory, and ultrasonographic characteristics associated with gallbladder disease and rupture in dogs. DESIGN: Retrospective case series. ANIMALS: 45 client-owned dogs. PROCEDURES: Medical records of dogs with histologically confirmed gallbladder disease that had ultrasonographic evaluation were reviewed. Signalment, history, clinical signs, laboratory values, bacteriologic culture of bile, gallbladder status at surgery or necropsy (intact vs ruptured), histopathologic findings, radiographic findings, ultrasonographic findings, and outcome were analyzed. RESULTS: The most common ultrasonographic findings were echogenic peritoneal fluid, thickened or laminated gallbladder wall, and echogenic reaction in the gallbladder fossa. Eighteen of 45 (40%) dogs had gallbladder rupture. Rupture was associated with histologic evidence of gallbladder necrosis, decreased serosal detail radiographically, and pericholecystic echogenic reaction, pericholecystic echogenic fluid, and generalized echogenic abdominal effusion ultrasonographically. Twenty-one of 45 (47%) dogs had mucocele, and 9 (43%) of those had gallbladder rupture. Eleven of 40 dogs had positive results of bacteriologic culture, and 5 of those had gallbladder rupture. Only 2 dogs had concurrent positive results of bacterial bile culture and gallbladder mucocele. Survival rate was 86% and not significantly related to presurgical bile leakage, positive results of bacterial culture, or mucocele. CONCLUSIONS AND CLINICAL RELEVANCE: Ultrasonographic findings of pericholecystic reaction, localized or generalized echogenic peritoneal fluid, or decreased radiographic peritoneal detail should raise the index of suspicion for gallbladder rupture. Mucocele or bacterial gallbladder infection was the most common concurrent finding in dogs with gallbladder rupture.

Radiographic findings in dogs with pulmonary blastomycosis: 125 cases (1989-2006).

OBJECTIVE: To identify radiographic patterns in dogs with pulmonary blastomycosis and radiographic factors associated with outcome. DESIGN: Retrospective case series. ANIMALS: 125 dogs with pulmonary blastomycosis. PROCEDURES: Medical records were reviewed, and for each lung lobe, the primary radiographic pattern and percentage of lobar involvement at the time of initial examination were recorded. RESULTS: 79 dogs survived, 38 died, and 8 were euthanized without treatment. The initial radiographic pattern was variable and not significantly associated with outcome. Mean half-time for radiographic resolution of pulmonary infiltrates was 41.4 days for all patterns except masses, for which mean half-time to resolution was 90.8 days. Transient radiographic worsening was seen in 20 of 87 (23%) dogs but was not associated with a poor prognosis. Pulmonary bullae were seen in 20 (16%) dogs, most often in association with an alveolar pattern. Accuracy of using percentage of right caudal lung lobe involvement ( 20%) to predict outcome was 74.4%; accuracy of using number of affected lobes (< 4 vs >or= 4) to predict outcome was 65.8%. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that a nonuniform distribution of pulmonary infiltrates was equally as likely as a diffuse nodular interstitial pattern in dogs with pulmonary blastomycosis. On the basis of half-time for resolution of pulmonary infiltrates, follow-up radiography should be performed no more often than every 4 to 6 weeks in clinically stable patients. Transient radiographic worsening that occurred during the initial weeks of treatment was not associated with a poorer prognosis.

Utility of diagnostic tests for and medical treatment of pulmonary blastomycosis in dogs: 125 cases (1989-2006).

OBJECTIVE: To compare results of the most common diagnostic tests for pulmonary blastomycosis in dogs, identify factors associated with outcome, and determine response to various antifungal treatment protocols. DESIGN: Retrospective case series. ANIMALS: 125 dogs with pulmonary blastomycosis. PROCEDURES: Medical records were reviewed, and information was obtained regarding diagnostic methods, results of routine laboratory testing, and radiographic response to antifungal treatment. RESULTS: 79 dogs survived, 38 died, and 8 were euthanized. Transthoracic fine-needle aspiration and transtracheal lavage were the most common diagnostic methods. Results of an agar gel immunodiffusion test for antibodies against Blastomyces dermatitidis were negative in 12 of 24 (50%) dogs. Only 3 of 94 (3.2%) dogs in which cytologic or histologic examination or bacterial culture of pulmonary samples were performed had any evidence of concurrent bacterial infection. The half-time for radiographic resolution of pulmonary infiltrates did not vary significantly with antifungal treatment, and use of a loading dosage of itraconazole was not associated with significant improvements in outcome or time to disease resolution. Dogs that died had a higher number of band neutrophils at initial examination, compared with those that survived. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that the agar gel immunodiffusion test should not be used as the sole diagnostic test for pulmonary blastomycosis in dogs, that concurrent bacterial pneumonia was uncommon in dogs with pulmonary blastomycosis, and that the rate with which pulmonary infiltrates resolved did not vary significantly among antifungal treatments.

Evaluation of total and ionized calcium status in dogs with blastomycosis: 38 cases (1997-2006).

OBJECTIVE: To determine blood ionized calcium (iCa) and serum total calcium (tCa) concentrations in dogs with blastomycosis and to evaluate whether serum tCa concentration, albumin-adjusted serum calcium concentration (AdjCa-Alb), and total protein-adjusted serum calcium concentration (AdjCa-TP) accurately predict iCa status. DESIGN: Retrospective case series. ANIMALS: 38 client-owned dogs with a cytologic diagnosis of blastomycosis. PROCEDURES: Dogs were classified as hypocalcemic, normocalcemic, or hypercalcemic on the basis of blood iCa concentration, serum tCa concentration, AdjCa-Alb, and AdjCa-TP; classification on the basis of serum tCa concentration, AdjCa-Alb, and AdjCa-TP was compared with blood iCa concentration. RESULTS: Except for 2 hypercalcemic dogs, all dogs had blood iCa concentrations within the reference interval. Use of serum tCa concentration overestimated hypocalcemia in 57.9% (22/38) of dogs and underestimated hypercalcemia in 1 dog. Use of AdjCa-Alb correctly reclassified all dogs as normocalcemic that were classified as hypocalcemic on the basis of serum tCa concentration, but failed to predict hypercalcemia in 1 dog. Use of AdjCa-TP correctly reclassified all but 2 dogs as normocalcemic that were classified as hypocalcemic on the basis of serum tCa concentration, and failed to predict hypercalcemia in 1 dog. No correlation was found between blood iCa concentration and serum concentrations of tCa, total protein, and albumin; AdjCa-Alb; or AdjCa-TP. CONCLUSIONS AND CLINICAL RELEVANCE: High blood iCa concentration was uncommon in dogs with blastomycosis. Hypoalbuminemia contributed to a low serum tCa concentration despite a blood iCa concentration within reference limits. The use of serum tCa concentration, AdjCa-Alb, and AdjCa-TP may fail to identify a small number of dogs with high blood iCa concentrations.

Electrolyte distribution and yolk sac morphology in frozen hydrated equine conceptuses during the second week of pregnancy.

To investigate how equine conceptuses expand rapidly despite the hypo-osmolality of their yolk sac fluid, 18 conceptuses, aged 8-12 days and 0.8-10.0 mm in diameter, were examined by cryoscanning electron microscopy and energy dispersive X-ray microanalysis to determine the distribution of Na, Cl and K in their fluids. No osmotic gradient was found between central and peripheral yolk sac fluid. In conceptuses > or = 6 mm in diameter, the concentrations of both Na and K in the subtrophectodermal compartments were higher than those determined previously in uterine fluid, supporting the concept of osmotic intake of fluid from the uterine environment as far as the compartments. However, electrolyte concentrations in the compartments consistently exceeded those found in the yolk sac, making it likely that 'uphill' water transport, rather than a purely osmotic uptake, is involved in yolk sac fluid accumulation. We also speculate that capsule formation could actively contribute to conceptus expansion and thereby to fluid intake.

Mucilage production by wounded xylem tissue of maize roots - time course and stimulus.

As a reaction to invasion by pathogens, plants block their xylem conduits with mucilage, restricting pathogen advance. Wounding soil-grown roots of maize revealed that pectinaceous mucilage could be found in the vessels after 6 h, and abundantly filled most vessels up to 3 cm proximal to the wound after 1 d. Phenolics increased in the mucilage at later times. The same reactions occurred in vessels following mechanical wounding of axenically-grown roots, showing that the presence of microbes is not necessary for the response. The xylem mucilage is similar to root-cap mucilage in mode of extrusion from the periplasmic space of living cells through primary wall, apparent phase transition, and staining indicative of acidic polysaccharides. Whether other known properties of root-cap mucilage which might alter vessel functioning, such as reduction of surface tension and increased viscosity produced by dissolved solutes, are also common to xylem mucilage requires further investigation. However, our results indicate that possible influence of wounding-induced mucilage in xylem vessels should be considered in all experimental investigations of xylem function.

Antifungal and cancer cell growth inhibitory activities of 1-(3',4',5'-trimethoxyphenyl)-2-nitro-ethylene.

The antifungal and cancer cell growth inhibitory activities of 1-(3',4',5'-trimethoxyphenyl)-2-nitro-ethylene (TMPN) were examined. TMPN was fungicidal for the majority of 132 reference strains and clinical isolates tested, including those resistant to fluconazole, ketoconazole, amphotericin B or flucytosine. Minimum fungicidal concentration/minimum inhibitory concentration (MFC/MIC) ratios were < or = 2 for 96% of Cryptococcus neoformans clinical isolates and 71% of Candida albicans clinical isolates. TMPN was fungicidal for a variety of other basidiomycetes, endomycetes and hyphomycetes, and its activity was unaffected by alterations in media pH. The frequency of occurrence of fungal spontaneous mutations to resistance was <10(-6). Kill-curve analyses confirmed the fungicidal action of TMPN, and demonstrated that killing was concentration- and time-dependent. At sub-MIC exposure to TMPN, C. albicans did not exhibit yeast/hyphae switching. TMPN was slightly cytotoxic for murine and human cancer cell lines (GI50=1-4 microg ml(-1)), and weakly inhibited mammalian tubulin polymerization (IC50=0.60 microg ml(-1)).