Hands-on Gross Anatomy Instruction Improves Clinical Imaging Skills Among Cardiovascular Fellows.

INTRODUCTION: Multi-modality imaging is a crucial component of cardiovascular (CV) fellowship training and requires knowledge of CV anatomy for interpretation. We hypothesized that hands-on anatomy education would improve the imaging interpretation skills of CV fellows. METHODS: The first-year CV fellowship class completed a hands-on cadaveric anatomy session correlated with clinical imaging. Fellows' ability to identify CV structures on cardiac imaging was assessed using a 30-question assessment tool administered at baseline and 1 week and 6 months post intervention. Advanced CV fellows (second or third year) who had not attended the session were also tested. Scores were expressed as median [interquartile range]. RESULTS: Among 9 first-year fellows, the majority reported no formal anatomy training since medical school (N = 7) and rated their knowledge of CV anatomy as fair or poor (N = 7) prior to the intervention. The median assessment score was higher 1 week after intervention vs baseline (24 [23-25] vs 19 [17-21]; P = .013) and remained higher than baseline at 6 months (26 [26-28] vs 19 [17-21]; P = .009). The 6-month post-intervention score for first-year fellows was not significantly different than that of senior fellows (n = 10) not exposed to the intervention (26 [26-28] vs 26 [23-27]; P = .434). CONCLUSIONS: Gross anatomy instruction improved first-year CV fellows' interpretation of CV imaging. Anatomic instruction may be a useful adjunct to multi-modality imaging education.

Recombinant adeno-associated virus-mediated correction of lysosomal storage within the central nervous system of the adult mucopolysaccharidosis type VII mouse.

The central nervous system (CNS) is a predominant site of involvement in several lysosomal storage diseases (LSDs); and for many patients, these diseases are diagnosed only after the onset of symptoms related to the progressive accumulation of macromolecules within lysosomes. The mucopolysaccharidosis type VII (MPS VII) mice are deficient for the lysosomal enzyme beta-glucuronidase and, by early adulthood, develop a significant degree of glycosaminoglycan storage within neuronal, glial, and leptomeningeal cells. Using this animal model, we investigated whether gene transfer mediated by a recombinant adeno-associated virus (rAAV) vector is capable of reversing the progression of storage lesions within the CNS. Adult MPS VII mice received intracerebral injections of 4 X 10(7) infectious units of a rAAV vector carrying the murine beta-glucuronidase (gus-s(a)) cDNA under the transcriptional direction of the cytomegalovirus immediate-early promoter and enhancer. By 1 month after vector administration, transgene-derived beta-glucuronidase was present surrounding the injection site. Enzyme levels were between 50 and 240% of that found in wild-type mice. This level of beta-glucuronidase activity was sufficient to reduce the degree of lysosomal storage. Moreover, the reduction in storage was maintained for at least 3 months post-rAAV administration. These data demonstrate that rAAV vectors can transduce the diseased CNS of MPS VII mice and mediate levels of transgene expression necessary for a therapeutic response. Thus, rAAV vectors are potential tools in the treatment of the mucopolysaccharidoses and other lysosomal storage diseases.

Gene transfer to the intestinal tract: a new approach using selective injection of the superior mesenteric artery.

Gene transfer to the intestinal tract has many potential applications, including complementation of single gene disorders, genetic immunization, and ectopic production of therapeutic molecules. Because the intralumenal approach to vector administration has not been highly successful, we tested whether the circulation can be used as a route to transfer genes to intestinal cells. The superior mesenteric artery (SMA) and vein (SMV) of adult Lewis rats were isolated and an adenoviral vector expressing the Escherichia coli LacZ gene was injected into the SMA. In one set of experiments, both vessels remained patent throughout the entire procedure. In a second group of animals, both vessels were occluded by clamping the SMA 1 cm distal to the injection site and the SMV proximal to the portal vein. In the absence of vascular clamps, gene transfer was evident throughout the small bowel, localized near the serosal surface within the muscularis propria. Occlusion of the SMA and SMV limited gene delivery to a short segment of bowel and shifted beta-galactosidase activity toward the mucosal surface. At the level of microscopy, most of the transduction events were in the lamina propria; transduced mucosal epithelial cells were occasionally observed. These data demonstrate that intestinal gene transfer can be accomplished through the circulation, and that targeting specific regions is feasible.

Use of fluconazole in the treatment of candidal endophthalmitis.

Candidal endophthalmitis is a sight-threatening ocular infection that most frequently occurs as a complication of candidemia. While amphotericin B is considered the gold standard for the treatment of most invasive fungal infections, the optimal management of candidal endophthalmitis has not been determined. Fluconazole, a triazole antifungal agent, has been shown to be effective in the management of a number of invasive fungal infections in both immunocompromised and immunocompetent hosts. We describe the clinical features and outcomes for six patients with candidal endophthalmitis who were treated with fluconazole at our institutions, and we review 21 additional cases reported in the English-language literature. In total, fluconazole has been used as the sole therapy for candidal endophthalmitis in 14 patients; 16 eyes were infected. Endophthalmitis was cured in 15 of 16 eyes (94%), including five infections that were complicated by vitreitis. Successful treatment required the administration of fluconazole (100-200 mg po) daily for approximately 2 months. In addition, fluconazole has been used in combination with pars plana vitrectomy for the successful treatment of four cases of candidal endophthalmitis that were complicated by moderate to severe vitreitis. Fluconazole appears to be a safe and effective alternative or addition to conventional treatments for the management of candidal endophthalmitis. Prospective evaluation is required to more clearly define the role of this antifungal agent in the management of ocular infections due to Candida species.

Blood-brain barrier permeability in an experimental model of bacterial cerebritis.

The mechanisms affecting blood-brain barrier (BBB) permeability in a brain abscess are not well defined. We sought to determine whether one bacterial species, Staphylococcus aureus, when inoculated into the brain, can cause the BBB to become abnormally permeable before leukocytes begin migrating into the brain. Cerebritis was induced by inoculating a suspension of S. aureus into the brain of the rat. The extent of leukocyte migration into the brain was assessed from histological sections at sequential times after the injection. BBB permeability was assessed by 1) detecting the presence of serum albumin leakage into the brain with a fluorescein-labeled antibody to rat albumin, and 2) detecting evidence of staining of the brain parenchyma with Evans blue dye. The fluorescein labelled anti-rat albumin antibody studies showed that the BBB was immediately damaged in experimental and control animals by the process of inoculation, but remained open to a greater extent in subjects inoculated with bacteria. Within 6 hours after inoculation, neutrophils began migrating into bacteria-inoculated brains. Evans blue dye, however, did not become detectable in the surrounding parenchyma until 72 hours later, long after leukocyte migration had occurred. The findings indicate that an acute disruption of the BBB in the needle track precedes leukocyte influx, but a more widespread increase in regional BBB permeability does not occur until 3 days after the bacterial inoculation. The time course for the development of increased vascular permeability suggests that a delayed product of the inoculation caused impairment of the regional BBB.

The effects of galactosamine-induced hepatic failure upon blood-brain barrier permeability.

The role of changes in blood-brain barrier permeability in the pathogenesis of hepatic encephalopathy remains uncertain. To test the hypothesis that brain microvessel permeability is nonselectively increased in hepatic encephalopathy we measured the blood-brain barrier permeability-surface area product in rats with acute liver failure induced by intraperitoneal injection of galactosamine. The permeability-surface area products to the diffusion-limited tracers, sucrose and methylaminoisobutyric acid, were determined as a measure of blood-brain barrier permeability. Animals were examined 24, 36 and 42 hr after injection, at times when they were stuporous, but not comatose. No significant elevations of the permeability-surface area products for either compound were detected in clinically affected experimental animals when compared to controls. Our results indicate there is no generalized increase in brain vascular permeability during hepatic insufficiency in precomatose animals.

Invasive external otitis: review of 12 cases.

Invasive external otitis is an infection caused by Pseudomonas aeruginosa that often occurs in elderly people with diabetes. Twelve cases that illustrate the problems associated with the clinical recognition and successful outcome of the condition were reviewed. The patients' average age was 62.5 years, and they had been ill for an average of 1.8 months before admission to hospital. Predisposing factors included diabetes, swimming in a warm climate and the use of a hearing aid. Radionuclide bone scanning and surgical exploration revealed pathognomonic findings. Initial therapy was often suboptimal: one or more relapses occurred in seven of the patients. All of the patients were cured without relapse after a minimum of 4 weeks of therapy with tobramycin plus an anti-Pseudomonas penicillin. The average duration of the illness was 3.9 months. The outcome in invasive external otitis should be excellent if the condition is diagnosed early and appropriate therapy is instituted.

CT of pseudomembranous colitis.

A case is presented in which computed tomography of the abdomen was performed to search for possible peritoneal abscess. The incidental observation of an irregularly thickened wall of the colon led to the diagnosis of pseudomembranous colitis.

Acute respiratory failure due to strongyloidiasis in polymyositis.

Strongyloides stercoralis is an intestinal nematode which infects large numbers of the population of tropical and subtropical geographic zones. Autoinfection permits the parasite to persist in asymptomatic hosts for years after they leave the tropics. Occasionally, in immunosuppressed patients, massive pulmonary or systemic invasion occurs. We report such an event in a corticosteroid treated patient with severe polymyositis. The life cycle of this parasite and the potential for overwhelming infestation are reviewed. As immunosuppressive therapy becomes more routine in rheumatic diseases, the rheumatologist should be aware of this sinister opportunistic pathogen.

Confirmation of a computer-derived nomogram to predict gentamicin serum concentrations in postsurgical patients.

The applicability of a previously reported nomogram to predict serum gentamicin levels in postsurgical patients was investigated. Seventeen patients accounting for 20 courses of gentamicin were studied. A total of 72 peak serum gentamicin levels were measured by a microbiological assay and compared with predicted serum levels determined by the dosing nomogram. Eighty-five percent of the measured peak gentamicin serum levels agreed with nomogram-predicted levels. This figure was reduced to 65% when certain unforeseen factors (i.e., patient interference with intravenous lines, dosage miscalculation and extra routes of gentamicin elimination) were identified. The nomogram is a particularly useful tool for the clinician to whom serum gentamicin levels are unavailable and who needs a method to predict serum gentamicin concentration based upon a given dosage.

Antibiotic synergy and antagonism against clinical isolates of Klebsiella species.

Minimal inhibitory concentrations of kanamycin, gentamicin, amikacin, cephalothin, and chloramphenicol were determined in Trypticase soy broth for 70 clinical isolates of Klebsiella species. Gentamicin and amikacin were the most active on a weight basis. Chloramphenicol was more active than kanamycin, and cephalothin was the least active of all. Studies using a microtiter modification of the checkerboard technique were performed to evaluate the comparative activity of the three aminoglycosides in combination with either chloramphenicol or cephalothin. The cephalothin-aminoglycoside combinations demonstrated synergy in >80% of the isolates tested. No antagonism was noted. The chloramphenicol-aminoglycoside combinations showed antagonism in 35 to 45% of the isolates tested. The data suggest that the chloramphenicol-aminoglycoside combinations be used with caution when treating serious infections where Klebsiella is a potential pathogen.

Stability of gentamicin sulfate injection following unit dose repackaging.

The potency of gentamicin sulfate following repackaging in disposable syringes were determined by a modification of the agar diffusion bioassay, using a highly gentamicin-resistant strain of Psuedomonas aeruginosa to assay milligram quantities of active drug. Three factors were studied at 30, 60 and 90 days: (1) syringe character (glass vs plastic); (2) temperature (25 C vs 4 C); and (3) volume of aspirated sample. Glass syringes were superior at all time intervals. Storage in plastic for even 30 days resulted in unacceptable loss of potency (greater than 15%) and formation of a brown precipitate. Mass spectrophotometry indicated that this precipitate consisted mainly of esters of phthalic acid (plasticizer) and methylparaben (gentamicin preservative). Temperature had no effect on retained potency. A positive correlation between the percent potency lost and volume of gentamicin aspirated was demonstrated in both glass and plastic.

Fatal Neisseria (Branhamella) catarrhalis pneumonia in an immunodeficient host.

A 64-year-old man with far-advanced IgA multiple myeloma presented with fulminant and rapidly fatal bronchopneumonia. Gram stains of expectorated sputum and of transtracheal aspirate revealed gram-negative intracellular and extracellular diplococci. Cultures of these specimens yielded Neisseria catarrhalis. Subsequent histologic examination of the lung confirmed the presence of numerous gram-negative diplococci in the alveolar spaces. The pathogenic potential of this nasopharyngeal commensal is discussed in both the normal and the immunosuppressed host.