Influence of Small Vessel Disease and Microstructural Integrity on Neurocognitive Functioning in Older Individuals: The DANTE Study Leiden.

BACKGROUND AND PURPOSE: Small vessel disease is a major cause of neurocognitive dysfunction in the elderly. Small vessel disease may manifest as white matter hyperintensities, lacunar infarcts, cerebral microbleeds, and atrophy, all of which are visible on conventional MR imaging or as microstructural changes determined by diffusion tensor imaging. This study investigated whether microstructural integrity is associated with neurocognitive dysfunction in older individuals, irrespective of the conventional features of small vessel disease. MATERIALS AND METHODS: The study included 195 participants (75 years of age or older) who underwent conventional 3T MR imaging with DTI to assess fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity. Cognitive tests were administered to assess cognitive domains, and the Geriatric Depression Scale-15 and Apathy Scale of Starkstein were used to assess symptoms of depression and apathy, respectively. The association between DTI measures and neurocognitive function was analyzed by using linear regression models. RESULTS: In gray matter, a lower fractional anisotropy and higher mean diffusivity, axial diffusivity, and radial diffusivity were associated with worse executive function, psychomotor speed, and overall cognition and, in white matter, also with memory. Findings were independent of white matter hyperintensities, lacunar infarcts, and cerebral microbleeds. However, after additional adjustment for normalized brain volume, only lower fractional anisotropy in white and gray matter and higher gray matter radial diffusivity remained associated with executive functioning. DTI measures were not associated with scores on the Geriatric Depression Scale-15 or the Apathy Scale of Starkstein. CONCLUSIONS: Microstructural integrity was associated with cognitive but not psychological dysfunction. Associations were independent of the conventional features of small vessel disease but attenuated after adjusting for brain volume.

[Right-ventricular dysfunction and the pulmonary vascular obstruction index: predictable variables of the clinical course over 3 months in patients with acute lung emboli]. / Rechterventrikeldisfunctie en index voor pulmonale vasculaire obstructie: voorspellende variabelen voor het klinische beloop gedurende 3 maanden bij patiënten met acute longembolie.

OBJECTIVE: To quantify right-ventricular dysfunction and the pulmonary artery obstruction index, in patients with acute pulmonary embolism, using helical CT, and to assess the prognostic value of these parameters. DESIGN: Prospective. METHOD: In 120 consecutive patients with proven acute pulmonary embolism, the extent of right-ventricular dysfunction was assessed by quantifying the ratios of the right to left-ventricular short-axis diameters (RV/LV ratio) and the extent ofobstruction ofthe pulmonary-artery circulation by using helical CT images. Regression analysis was used to correlate these parameters with patient outcome. RESULTS: Right-ventricular dysfunction (RV/LV ratio > 1.0) was seen in 69 patients (57.5%). Seven patients died as a direct result of pulmonary embolism. Both the RV/LV ratio and the obstruction index were significant risk factors for mortality within three months (p = 0.04 and 0.01 respectively). The positive predictive value for pulmonary embolism-related mortality of an RV/LV ratio > 1.0 was 10.1% (95% CI: 2.9-17.4). The negative predictive value for an uneventful outcome of an RV/LV ratio < or = 1.0 was 100% (95% CI: 94.3-100). There was a 11.2-fold risk of dying of pulmonary embolism in patients with an obstruction index > or = 40% (95% CI: 1.3-93.6). CONCLUSION: Markers of right-ventricular dysfunction and pulmonary vascular obstruction, assessed by helical CT-examination at baseline, help to predict mortality during follow-up of patients with acute pulmonary embolism.

Helical computed tomography and alternative diagnosis in patients with excluded pulmonary embolism.

OBJECTIVE: A clinical diagnosis of pulmonary embolism (PE) is confirmed objectively in 20-30% of patients. Helical computed tomography (CT) can allow an alternative diagnosis to be made. The frequency and validity of alternative diagnoses on helical CT in consecutive patients presenting with clinically suspected PE was assessed. PATIENTS AND METHODS: In all 512 prospectively analyzed patients helical CT scan was performed, and apart from presence or absence of PE, pathologic changes in lung parenchyma, mediastinum, cardiovascular system, pleura and skeleton were recorded. When possible an alternative diagnosis was given and compared with the final diagnosis after 3 months follow-up. RESULTS: In 130 patients (25.4%) PE was excluded and an alternative diagnosis considered likely. In 123 of the 130 patients (94.6%) this diagnosis was unchanged at 3 months follow-up. The diagnoses included pneumonia (n = 67), malignancy (n = 22), pleural fluid (n = 10), cardiac failure (n = 10), COPD (n = 6) and a variety of other causes (n = 15). The diagnosis changed at follow-up in seven patients (5.4%). An initial diagnosis of pneumonia changed to malignancy in two patients and to pleuritis and cardiac failure in one patient each. In two other patients malignancy and chronic obstructive pulmonary disease (COPD) were ruled out and the diagnosis changed to pneumonia. In one patient the final diagnosis remained unknown after an initial suspicion of malignancy. CONCLUSION: In clinically suspected PE helical CT allows a reliable alternative diagnosis to be made in 25.4% of patients. This feature is an unique advantage in comparison with other diagnostic tests and supports the decision of taking helical CT as first line test in suspected PE.

Effect of PD fluid instillation on the peritonitis-induced influx and bacterial clearing capacity of peritoneal cells.

BACKGROUND: The commonly used peritoneal dialysis fluids contain glucose as the osmotic agent. Heat sterilization leads to the formation of glucose degradation products which contribute, together with glucose, to the formation of advanced glycation end-products (AGEs). AGEs have been shown to be present in the peritoneal cavity. Methods have been developed to minimize the amount of glucose degradation products in peritoneal dialysis fluids. In a rat peritoneal dialysis model, we compare the effect of a commonly used peritoneal dialysis fluid, Gambrosol, with a newly developed peritoneal dialysis fluid, PD-Bio, on the influx and functional capacity of the peritoneal cells after 2 weeks of peritoneal dialysis fluid instillation. METHODS: Three groups of animals were used: rats received daily infusion with 15 ml of either 4% Gambrosol (group 1) or 4% PD-Bio (group 2), and a control group of animals did not receive fluid (group 3). After 2 weeks of PD fluid instillation, all the animals were injected with a 0.5 ml suspension containing 3x10(8) colony-forming units of Staphylococcus aureus. The in vivo bacterial clearing capacity was determined after 15 h. RESULTS: A statistically significant higher leukocyte influx was found in the control group compared with both PD fluid-injected groups. No statistical differences in bacterial clearing were observed among the three groups, although the number of bacteria recovered from the PD-Bio group tended to be lower than that from the Gambrosol group. Moreover, in both PD fluid instillation groups, the bacteria tended to be cleared more slowly compared with the control group. The number of mesothelial cells in the PD fluid groups was significantly greater than in the control group. CONCLUSION: No differences were observed in bacterial clearing capacity, leukocyte influx and mesothelial cell number after a 2 week exposure of the peritoneal cavity to Gambrosol vs PD-Bio.

Validation of a questionnaire on medical drug use during pregnancy.

The validity of a questionnaire on medical drug use during pregnancy was tested against information collected 7 years previously (in 1983-1984) at the University Hospital of Nijmegen, the Netherlands. The study population consisted of women with high-risk pregnancies. The sensitivity for drug categories varied between 0% and 80%. The sensitivity was highest for drugs used during labor (77%) and was extremely low (0%) for some drug categories. Personal characteristics thought to influence the sensitivity, such as parity of the mother and method of data collection (postal questionnaire or personal interview), showed no statistically significant effect. The newly developed questionnaire needs further improvement.

Use of monoclonal antibodies to keratin 7 in the differential diagnosis of adenocarcinomas.

Monoclonal antibodies (MAbs) to specific keratin subtypes were prepared and characterized by immunoblotting and immunohistochemical assays on human cell cultures and normal and malignant human tissues. Chain-specific MAbs to keratin 7 (RCK 105, OV-TL 12/30) and keratin 18 (RGE 53, RCK 106, CK18-2), as well as broadly cross-reacting keratin MAbs (RCK 102, OV-TL 12/5) could be shown to react with different types of human epithelial tissues and were therefore tested for their usefulness in the differential diagnosis of carcinomas. The two broad-spectrum antibodies stained virtually all of the more than 350 carcinomas tested, especially when combined, and distinguished them from most nonepithelial tumors. The keratin 18 MAbs distinguished adenocarcinomas (which are keratin 18 positive) from most squamous cell carcinomas (which are generally keratin 18 negative). The MAbs to keratin 7 could be shown to recognize specific subtypes of adenocarcinoma and could, for example, distinguish between ovarian carcinomas (keratin 7 positive) and carcinomas of the gastrointestinal tract (keratin 7 negative), or between transitional cell carcinomas (keratin 7 positive) and prostate cancer (keratin 7 negative). In general, malignancies showed the expected keratin reactivity pattern as concluded from the keratin pattern of its cell of origin or its type of differentiation. The use of an extended series of malignancies did, however, also illustrate that exceptions to this rule exist. For example, certain antibodies to keratin 18 stained tumor areas in squamous cell carcinomas of the lung. Also a certain percentage of tumors, which generally showed no keratin 7 expression, were positive with RCK 105 or OV-TL 12/30. On the other hand, a certain percentage of tumors, which were generally positive for keratin 7, did not show a staining reaction with these MAbs. Furthermore subtle differences between reactivity patterns of different MAbs recognizing the same keratin protein were observed, both in the normal and malignant human tissues, indicating that specific keratin epitopes may be masked in certain tissues and that unmasking of such epitopes can occur with malignant progression. This phenomenon may be of some use in a further subtyping of carcinomas, especially those of the gastrointestinal tract. Despite these exceptional staining patterns, the keratin MAbs described above have proved to be useful tools in the characterization of epithelial tumors in routine histopathology and cytopathology, in which they add to a more refined diagnosis of (adeno)carcinomas.

Distribution of cytokeratin polypeptides in human transitional cell carcinomas, with special emphasis on changing expression patterns during tumor progression.

The expression of cytokeratin (CK) polypeptides was studied in 59 transitional cell carcinomas (TCC) of the urinary tract of different grade and stage. Using a panel of 14 polypeptide-specific monoclonal CK-antibodies we identified immunohistochemically 8 different CKs separately, ie, CKs 4, 7, 8, 10, 13, 14, 18, and 19, while in immunoblotting studies CK5 expression was detected indirectly by using the antibody RCK102, recognizing CK5 + 8. In low-grade TCCs (G1-G2), the CK distribution was comparable to that in normal urothelium, however with a variable expression of CK13 in the different tumors and a uniform distribution of CK7. In higher-grade TCCs (G3), a decrease in CK13 expression was observed, particularly in the areas of muscle invasion. Furthermore, the appearance and increasing expression of CK14 (not present in normal urothelium or G1 TCCs) with higher grade and stage was striking. With tumor progression changes in epitope configurations of CK8 and CK18 were detected, as concluded from immunohistochemical assays with the panel of monoclonal antibodies for each of these two CKs. In extreme cases this resulted in differential staining patterns of the invasive and noninvasive components within one tumor. In 7 of 32 G3 TCCs, some of which showed areas with evident squamous differentiation, a decrease in the expression of CK7 and/or CK8 was seen. We conclude that tumor progression in TCCs is associated with discrete changes of CK expression, which can be detected using monoclonal antibodies.