Intratemporal vascular tumors: detection with CT and MR imaging

The diagnostic contributions of computed tomography (CT) and magnetic resonance (MR) imaging were compared in 12 patients with benign intratemporal vascular tumors (hemangioma or vascular malformation). The tumors included six in the internal acoustic canal and six in the geniculate ganglion region. Clinical and histologic correlations were made. Two of the six patients with tumors in the internal acoustic canal underwent CT, and both required gas cisternography to show the tumor. Five patients in that group underwent MR imaging, and all five studies showed the tumor. All six patients with geniculate ganglion tumors underwent CT. Results in one study were questionable, and five showed the tumor. Five patients in this group underwent MR imaging, but the MR findings were positive in only two cases. MR imaging should therefore be performed before CT in the evaluation of facial nerve dysfunction, as it demonstrated all tumors in the internal acoustic canal and some in the geniculate ganglion region. If MR findings are negative, CT should then be performed to rule out a possible geniculate ganglion lesion.     

Depletion of O6-alkylguanine-DNA alkyltransferase by O6-benzylguanine in three-dimensional collagen cultures of normal human breast epithelial cells.

O6-Alkylguanine--DNA alkyltransferase (AGT) is a protein which removes the promutagenic O6-alkylguanine lesion induced in DNA by alkylating agents. Our results demonstrate that freshly isolated organoids from reduction mammoplasty specimens contain significant levels of AGT activity. AGT activity in breast epithelial cells shows interindividual variation. Constitutive levels of AGT activity remain unchanged during short-term serum-free culture of breast epithelial cells inside three-dimensional rat-tail collagen gel matrix. In the present study, we optimized conditions for depleting AGT activity in human breast epithelial cells cultured in three-dimensional collagen gel matrix using O6-methylguanine and O6-benzylguanine which are substrates for AGT. AGT activity was efficiently inactivated by exposure of cells to O6-methylguanine or O6-benzylguanine. Inactivation with O6-benzylguanine was more rapid, of greater magnitude and consistency and occurred at lower concentrations than with O6-methylguanine. Near-complete inactivation (> 99.5%) of AGT activity was reproducibly achieved with 50 microM O6-benzylguanine. In contrast, 500 microM O6-methylguanine was needed to obtain a maximal effect and this reduced AGT activity by only 53-93% of control. Within 30 min of adding the free base, 50 microM O6-benzylguanine depleted 95% of the levels of AGT compared to 30% inhibition with 500 microM O6-methylguanine. The profile for restoration of AGT activity was different following a 24 h incubation and subsequent removal of each of the guanine derivatives. AGT activity levels remained undetectable for at least 2 days after removal of 50 microM O6-benzylguanine from the medium and recovered to only 53% of control values after an additional 3 days. AGT activity levels remained undetectable for at least 2 days after removal of 50 microM O6-benzylguanine from the medium and recovered to only 53% of control values after an additional 3 days. In contrast, following removal of 500 microM O6-methylguanine, the activity was restored from its nadir of 16% of control values reaching pretreatment levels after 5 days. These results suggest that treatment with O6-benzylguanine may be used to modulate the incidence of transforming mutations in cultured human breast epithelial cells treated with chemical carcinogens which give rise to O6-alkylguanine adducts.     

Case study of a patient with severe nephrotic syndrome

M.T. battled SLE for 9 years before renal failure occurred. She is now free of extrarenal symptoms of lupus, as has been described elsewhere (Ziff & Hilderman, 1983). The patient has regained here appetite, lost 13 pounds, recovered some strength and reestablished her social network. Without the severe proteinuria, M.T. has a chance to improve her nutritional status and increase her albumin. Her pulmonary status may also improve if she can refrain from smoking. Although fatigue is a debilitating feature of lupus, M.T. has increased stamina and is learning energy conservation techniques. Immediately after surgery, she did experience problems with bleeding, pneumonia, and pleural effusions, but the medical and nursing management prevented serious adverse outcomes. Fluid balance is no longer problematic, and M.T. is approaching her ideal body weight as her nutritional status improves. Her serum albumin has increased to about 2.6 gm/dl with some decrease in her proteinuria.     

Glutathione ester protects against hydroxynonenal-induced loss of auditory hair cells.

OBJECTIVE: Test the ability of glutathione monoethyl ester (GSH(e)) to protect auditory hair cells against the ototoxic effects of 4-hydroxy-2,3-nonenal (HNE). STUDY DESIGN AND SETTING: Organ of Corti explants were either untreated or treated with one of a series of four concentrations of GSH(e) for one day, then exposed to HNE. Counts of FITC-phalloidin-labeled hair cells determined both HNE ototoxicity and GSH(e) otoprotection. RESULTS: HNE was toxic to hair cells at physiologically relevant levels, eg, 400 muM, and GSH(e) provided a significant level of protection against HNE ototoxicity (P < 0.05) at all levels tested, ie, 1.16 to 9.3 mM. CONCLUSION: GSH(e) protects auditory hair cells from damage and loss initiated by a naturally occurring ototoxic molecule, ie, HNE (a by-product of oxidative stress). SIGNIFICANCE: Treatment with GSH(e) may be an effective therapy to protect the cochlea against the adverse effects of traumas (eg, electrode insertion) that generate oxidative stress.     

Acute peripheral arterial and graft occlusion: treatment with selective infusion of urokinase and lysyl plasminogen

Thirty-five patients hospitalized for recent angiographically documented arterial occlusion in the legs (27 femoropopliteal arteries and eight grafts) benefited from local fibrinolytic therapy delivered at the site of the occlusion with a 4- or 5-F catheter. This therapy combined a continuous urokinase (UK) infusion of 1,000 U/kg/hour and a lysyl plasminogen (LYS-PLG) infusion of 15 microkatals every 30 minutes. Angiographically confirmed lysis was obtained in 85% of the cases. Only 3% of the patients had major and 6% had minor groin hematomas. Only two patients had concentrations of fibrinogen as low as 100 mg/dl. Intravascular infusion of UK-LYS-PLG is as effective as streptokinase. Its excellent tolerance makes it a good alternative in the treatment of acute ischemia in the lower limbs.     

Congenital left atrial wall aneurysm in a patient with neurofibromatosis

A congenital intrapericardial aneurysmal dilatation of the left atrial wall was found in a 28 year old man who presented with atrial fibrillation after a syncopal event. The patient had cutaneous manifestations of neurofibromatosis. The diagnosis was made by cross sectional echocardiography and confirmed by angiocardiography. Surgical excision of the aneurysm resolved the symptoms.     

Evaluation of clinical criteria for the acute respiratory distress syndrome in pediatric patients.

OBJECTIVE: The primary goal of this study was to evaluate the validity of the North American-European Consensus Committee (NAECC) definition for acute respiratory distress syndrome (ARDS) in pediatric patients. A secondary aim was to evaluate the threshold value for the PaO2/FiO2 ratio, used to determine which pediatric patients have ARDS. DESIGN: Retrospective cohort study. SETTING: Pediatric intensive care unit. PATIENTS: Pediatric intensive care unit patients who required mechanical ventilation, died, and underwent autopsy between January 1, 1996, and December 31, 2002 (n = 34). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Clinical and chest radiograph information was collected retrospectively through chart review using a standardized data collection tool. Data included the criteria specified in the NAECC definition of ARDS and demographic information. We calculated the sensitivity, specificity, positive predictive value, negative predictive value, and likelihood ratio of clinical diagnosis of ARDS compared with a pathologic diagnosis. The threshold value of PaO2/FiO2 was identified by plotting receiver operating characteristics curves and comparing the areas under the curves. The NAECC definition yielded a sensitivity of 80.7% (95% confidence interval 60-92%), specificity of 71.4% (95% confidence interval 30-95), positive predictive value of 91.3% (95% confidence interval 70-98), negative predictive value of 50.0% (95% confidence interval 20-78), and likelihood ratio of 2.82. A PaO2/FiO2 <150 had a slightly higher (but not significantly different) specificity for ARDS than a value >200 (71% vs. 86%, p = .15) without changing sensitivity. CONCLUSIONS: Our study suggests the need for further research with larger number of children to identify an optimal Pao2/Fio2 threshold for identifying ARDS in this population.