Severe odontogenic infection in pregnancy: a timely reminder

Dental practitioners often treat patients that are pregnant. Understanding the altered physiology in the pregnant patient, especially changes in immune function, is vital in effective management of orofacial infections. We present a case of rapidly spreading odontogenic infection in a pregnant patient requiring surgical management. We also discuss the physiological changes of pregnancy relevant to dentistry, and the principles of managing such infections in the gravid patient.     

Vascular permeability in cerebral cavernous malformations

Patients with the familial form of cerebral cavernous malformations (CCMs) are haploinsufficient for the CCM1, CCM2, or CCM3 gene. Loss of corresponding CCM proteins increases RhoA kinase-mediated endothelial permeability in vitro, and in mouse brains in vivo. A prospective case-controlled observational study investigated whether the brains of human subjects with familial CCM show vascular hyperpermeability by dynamic contrast-enhanced quantitative perfusion magnetic resonance imaging, in comparison with CCM cases without familial disease, and whether lesional or brain vascular permeability correlates with CCM disease activity. Permeability in white matter far (WMF) from lesions was significantly greater in familial than in sporadic cases, but was similar in CCM lesions. Permeability in WMF increased with age in sporadic patients, but not in familial cases. Patients with more aggressive familial CCM disease had greater WMF permeability compared to those with milder disease phenotype, but similar lesion permeability. Subjects receiving statin medications for routine cardiovascular indications had a trend of lower WMF, but not lesion, permeability. This is the first demonstration of brain vascular hyperpermeability in humans with an autosomal dominant disease, as predicted mechanistically. Brain permeability, more than lesion permeability, may serve as a biomarker of CCM disease activity, and help calibrate potential drug therapy.     

Concomitant administration of granulocyte transfusions and amphotericin B in neutropenic patients: absence of significant pulmonary toxicity

One hundred and ninety-five series of granulocyte transfusions in 144 patients were evaluated with respect to possible severe pulmonary toxicity from concomitant administration of granulocytes and amphotericin B. Dyspnea as a side effect of granulocyte transfusion was equally common among patients receiving amphotericin B and those in a matched control group not receiving amphotericin B. Granulocyte transfusions and amphotericin B were given simultaneously in 35 transfusion series, involving 32 patients. Respiratory deterioration, defined as the appearance of new pulmonary infiltrates on chest x-ray, occurred in 11 of these 35 episodes. Patients developing respiratory deterioration were similar to those not developing respiratory deterioration in age, diagnosis, disease status, duration of concomitant therapy, and outcome, but more often had positive fungal cultures as an indication for treatment (91% versus 58%; p = 0.1). In 8 patients, the episodes of respiratory deterioration were readily explained by congestive heart failure, by simultaneous bacteremia or fungemia, or by fungal pneumonia discovered at autopsy. One patient had a leukoagglutinin reaction (responsive to steroids) and the other 2 had unexplained, but reversible respiratory deterioration. We concluded that concomitant administration of granulocyte transfusions and amphotericin B is not associated with unexpected or rapidly fatal pulmonary toxicity and when appropriate, can be safely accomplished.     

Metabolism of ara-C by blast cells from patients with ANLL

The dose-response relationship between extracellular concentration of cytosine arabinoside (ara-C) and intracellular formation of the putative active metabolites of ara-C [ara-C incorporation into DNA and intracellular pools of ara-C in triphosphate form (ara-CTP)] was investigated in blast cells obtained from patients with acute nonlymphocytic leukemia (ANLL) by exposing these cells in vitro to 10, 100, or 1,000 nmol/L of ara-C. We studied 23 untreated patients who subsequently achieved complete remission (CR) with a regimen using daunorubicin and conventional doses of ara-C (ara-C-sensitive group), and 30 patients judged to be ara-C-resistant either by failing initial induction therapy (16 patients) or by having relapsed on an ara-C- containing maintenance regimen (14 patients). In both patient groups, ara-C incorporation into DNA and intracellular ara-CTP both displayed statistically significant increases in response to increasing extracellular concentrations of ara-C (P = .0001 in both cases), with the rate of increase of ara-CTP greater than that of ara-C incorporation. Moreover, blast cells from all patients, even those who were most clinically resistant to ara-C, were able to form ara-CTP and to incorporate ara-C into DNA. Each tenfold increment in extracellular ara-C concentration caused an 8.5-fold increase in ara-CTP, but only a 3.6-fold increase in ara-C incorporation into DNA. Thus, the efficiency of incorporation of ara-C into DNA (defined as the ratio of ara-C incorporation to ara-CTP pools) decreased by 58% with each tenfold increment in the extracellular concentration of ara-C (P less than .0001), presumably as a result of the inhibitory effect of ara-CTP on DNA polymerase. Using an analysis of covariance, modest differences were found in the levels of the ara-C metabolite variables in the ara-C- sensitive group as compared with the resistant group. However, because there was considerable overlap in ara-C metabolite formation among the patient groups, it was not possible to predict clinical outcome by these in vitro assessments of ara-C metabolism.