Faculty Bibliography

Fungal endocarditis is an exceedingly rare complication of indwelling central venous catheters in adults. Here we describe what appears to be the first case of a right atrial thrombus superinfected with the yeast Torulopsis (Candida) glabrata and attached to an indwelling superior vena cava catheter that was not used for parenteral nutrition. A large vegetation-like mass adherent to the catheter tip was visualized by transesophageal echocardiography in a patient who presented with signs of septic pulmonary embolism. Following open-heart surgery, the definitive diagnosis was established by histopathologic examination of the surgical specimen

BACKGROUND: The pulmonary venous flow velocity pattern (PVFVP) in atrial septal defect (ASD) has not been previously studied in detail. Normally, PVFVP is primarily determined by the left heart performance. We hypothesized that the impact of left-sided heart dynamics on PVFVP is diminished in patients with ASD because of the presence of a left-to-right shunt into the low-resistance right side of the heart. METHODS AND RESULTS: Transesophageal echocardiography was performed in 19 adults and 3 children with a large, uncomplicated secundum ASD (maximum diameter 0.6 to 3.0 cm). All patients were in normal sinus rhythm with an average heart rate of 78 bpm in adults and 116 bpm in children. In 21 subjects the antegrade PVFVP lacked distinct systolic (S) and diastolic (D) waves. Instead, we observed a single continuous antegrade wave extending from the beginning of systole to the onset of atrial contraction. Furthermore, the amplitude of the atrial reversal (AR) wave was smaller than in historical controls. In 3 patients in whom ASD was surgically repaired, we observed an immediate return of distinct S and D waves postoperatively. This confirmed that PVFVP abnormality was indeed the result of the ASD. Also a large increase in the AR wave amplitude (46 + 15 cm/s) was noted postoperatively. CONCLUSIONS: This previously unrecognized PVFVP comprising a single continuous antegrade wave and a diminished AR wave sheds new light on the hemodynamics of ASDs. Its presence may also alert the echocardiographer to the possibility of an ASD when the septal defect cannot be visualized directly

In this review we describe characteristics of occupational airway diseases, as well as physical and chemical characteristics of agents inducing airway disease. Occupational airway diseases include industrial bronchitis, reactive airway dysfunction syndrome, bronchiolitis obliterans, and occupational asthma. High- and low-molecular weight substances associated with occupational airway disease are listed. The importance of host factors is stressed. Diagnostic approaches, particularly indicators for specific challenge testing with occupational materials, are described. Preventive and control measures are presented.

The eustachian valve directs oxygen-rich blood from the inferior vena cava toward the foramen ovale and away from the tricuspid valve during fetal development. Ordinarily, it does not prevent reflux of right atrial blood back into the inferior vena cava because it does not function as a true valve. Here we describe an unusual adult patient with severe tricuspid valve regurgitation in whom the eustachian valve did function as a true, albeit regurgitant, valve

Pneumocystis carinii is the causative agent of P. carinii pneumonia (PCP), an opportunistic infection associated with AIDS and other immunosuppressed conditions. Although polyamine metabolism of this fungus has been shown to be a chemotherapeutic target, this metabolism has not been thoroughly investigated. Reported here is the effect of one polyamine analogue, N, N'-bis[3-[(phenylmethyl)amino]propyl]-1,7-diaminoheptane (BBS), on P. carinii. BBS inhibits the growth of P. carinii in culture, but at concentrations higher than those required to inhibit the growth of other pathogens. However, BBS is at least as active in an animal model of PCP as in other models of diseases studied. BBS causes some reduction in P. carinii polyamine content and polyamine biosynthetic enzyme activities, but the effect is less than that observed with other pathogens and very much less than the effect of the polyamine biosynthesis inhibitor DL-alpha-difluoromethylornithine. BBS enters P. carinii cells via a polyamine transporter, unlike all other cells that have been studied. P. carinii cells do not remove the benzyl groups of BBS, as is reported for mammalian cells. The most likely mode of action is displacement of natural polyamines. Overall, the activity of BBS provides further evidence that polyamines and polyamine metabolism are rational targets for the development of drugs to treat PCP. Because the details of BBS-P. carinii interaction differ from those of other cells studied, polyamine analogues may provide a highly specific treatment for PCP

Since the incidence of aortic stenosis increases with age, physicians are likely to encounter this valvular disorder with greater frequency as populations continue to age. This paper provides a comprehensive overview of the etiology, natural history, pathophysiology, diagnosis, and management of aortic stenosis in the elderly. Echocardiography is the diagnostic modality of choice, suitable for the serial assessment of disease progression. Cardiac catheterization should be reserved mainly for the evaluation of possible concomitant coronary artery disease prior to cardiac surgery. Aortic valve replacement represents the only proven treatment modality for symptomatic, hemodynamically significant aortic stenosis. Advanced age is not a contraindication for surgery, and valve replacement can be performed in any patient with an acceptable surgical risk. (AJGC. 2000)

The rapid depletion of Pneumocystis carinii polyamines caused by in vitro exposure to DL-alpha-difluoromethylornithine (DFMO; also called eflornithine or Ornidyl) and the rapid repletion following removal of this drug suggested that the in vivo efficacy of DFMO against P. carinii pneumonia (PCP) may be limited by troughs in drug concentration resulting from the schedule of administration. This led to the prediction that, compared with the response to the standard animal protocol of administering DFMO in drinking water, the response of a rat model of PCP to DFMO would be lessened by bolus administration and improved by continuous infusion. These predictions were confirmed. Intraperitoneal bolus administration of up to 3 g of DFMO kg of body weight-1 was completely ineffective, although this dose has been shown to be effective when given in the drinking water. Conversely, continuous infusion improved the response against PCP seven- to ninefold over the response to drinking water administration. These findings suggest that, compared with the standard clinical investigational protocol for treatment of PCP with DFMO given in four divided daily doses, continuous infusion combined with monitoring of drug concentrations in plasma may improve efficacy and/or reduce the already low rate of adverse effects

Pneumocystis carinii pneumonia (PCP) can be treated with eflornithine (difluoromethylornithine, DFMO, Ornidyl), a competitive irreversible inhibitor of ornithine decarboxylase (ODC), a key enzyme for polyamine biosynthesis. Because ODC has been reported to be absent from P. carinii, it has been assumed that eflornithine affects P. carinii only indirectly, by affecting host polyamine biosynthesis. If this is true, then improvements in the selectivity of antipolyamine therapy for PCP would be limited. Since the presence of ODC in P. carinii is an important issue, a new search for this enzyme was made. Not only were initial assays negative, but P. carinii extract reduced the background catalytic action of pyridoxal-5'-phosphate, the coenzyme required by the enzyme. This suggested the presence of an inhibitor, which was further supported by the observation that a P. carinii extract could suppress a source of known ODC activity. The inhibitory activity could be removed by a desalting column or by dialysis, allowing detection of P. carinii ODC. Indirect evidence indicates that the inhibition is only apparent and is caused by unlabeled ornithine in the extract of P. carinii which interferes with the radiolabel-based assay system. P. carinii and host ODCs respond differently to changes in pH. P. carinii ODC is much less susceptible to inhibition by eflornithine than host ODC. The presence of ODC in P. carinii suggests that P. carinii ODC is the target of eflornithine and that P. carinii ODC may have sufficiently specific properties that inhibitors with improved selectivity against P. carinii ODC could be identified