Aphakic versus pseudophakic retinal detachments

Aphakic retinal detachments and pseudophakic retinal detachments (i.e., detachments following extracapsular cataract extraction and posterior chamber lens implant surgery) from the last 3 1/2 years were studied retrospectively. In the aphakic group, myopia (mean preoperative refraction -2.60) and intraoperative loss of vitreous (10.3%) were found to be risk factors. In the pseudophakic group, male patients predominated (21/26 = 80.8%); furthermore, myopia (mean preoperative refraction -4.60, mean axial length = 24.98 mm) was also a risk factor. Additional risk factors included intraoperative rupture of the capsule (11.5%) as well as postoperative Neodymium-YAG laser capsulotomy (34.6%). There was no appreciable difference between the two groups with regard to the type of detachment. In more than 50% of the cases, retinal tears occurred in the superior temporal quadrant. In 19.4% of the cases with pseudophakic retinal detachment, no foramen could be found; on the other hand, only in 7.7% of the cases in the aphakic group was no retinal hole seen. Surgery was anatomically successful in 92.3% of the pseudophakia cases. In the group with pseudophakic retinal detachment retinal surgery was only successful in 84.6% of the cases.     

Erythropoietin regulates hypoxic ventilation in mice by interacting with brainstem and carotid bodies

Apart from its role in elevating red blood cell number, erythropoietin (Epo) exerts protective functions in brain, retina and heart upon ischaemic injury. However, the physiological non-erythroid functions of Epo remain unclear. Here we use a transgenic mouse line (Tg21) constitutively overexpressing human Epo in brain to investigate Epo's impact on ventilation upon hypoxic exposure. Tg21 mice showed improved ventilatory response to severe acute hypoxia and moreover improved ventilatory acclimatization to chronic hypoxic exposure. Furthermore, following bilateral transection of carotid sinus nerves that uncouples the brain from the carotid body, Tg21 mice adapted their ventilation to acute severe hypoxia while chemodenervated wild-type (WT) animals developed a life-threatening apnoea. These results imply that Epo in brain modulates ventilation. Additional analysis revealed that the Epo receptor (EpoR) is expressed in the main brainstem respiratory centres and suggested that Epo stimulates breathing control by alteration of catecholaminergic metabolism in brainstem. The modulation of hypoxic pattern of ventilation after i.v. injection of recombinant human Epo in WT mice and the dense EpoR immunosignal observed in carotid bodies showed that these chemoreceptors are sensitive to plasma levels of Epo. In summary, our results suggest that Epo controls ventilation at the central (brainstem) and peripheral (carotid body) levels. These novel findings are relevant to understanding better respiratory disorders including those occurring at high altitude.     

Morphologic dysplasia in de novo acute myeloid leukemia (AML) is related to unfavorable cytogenetics but has no independent prognostic relevance under the conditions of intensive induction therapy: results of a multiparameter analysis from the German AML Cooperative Group studies.

PURPOSE: On the basis of cytomorphology according to the French-American-British (FAB) classification, we evaluated the prognostic impact of dysplastic features and other parameters in de novo acute myeloid leukemia (AML). We also assessed the clinical significance of the recently introduced World Health Organization (WHO) classification for AML, which proposed dysplasia as a new parameter for classification. PATIENTS AND METHODS: We analyzed prospectively 614 patients with de novo AML, all of whom were diagnosed by central morphologic analysis and treated within the German AML Cooperative Group (AMLCG)-92 or the AMLCG-acute promyalocytic leukemia study. RESULTS: Patients with AML M3, M3v, or M4eo demonstrated a better outcome compared with all other FAB subtypes (P <.001); no prognostic difference was observed among other FAB subtypes. The presence or absence of dysplasia failed to demonstrate prognostic relevance. Other prognostic markers, such as age, cytogenetics, presence of Auer rods, and lactate dehydrogenase (LDH) level at diagnosis, all showed significant impact on overall and event-free survival in univariate analyses (P <.001 for all parameters tested). However, in a multivariate analysis, only cytogenetics (unfavorable or favorable), age, and high LDH maintained their prognostic impact. Dysplasia was not found to be an independent prognostic parameter, but the detection of trilineage dysplasia correlated with unfavorable cytogenetics. CONCLUSION: Our results indicate that cytomorphology and classification according to FAB criteria are still necessary for the diagnosis of AML but have no relevance for prognosis in addition to cytogenetics. Our results suggest that the WHO classification should be further developed by using cytogenetics as the main determinant of biology. Dysplastic features, in particular, have no additional impact on predicting prognosis when cytogenetics are taken into account.     

Effects of ACE inhibition and bradykinin antagonism on cardiovascular changes in uremic rats

BACKGROUND: Cardiovascular death continues to be a major problem in renal failure. Structural abnormalities of the heart and the vasculature contribute to the increased cardiovascular risk. They are ameliorated by angiotensin-converting enzyme (ACE) inhibitors, but because of the nonspecifity of ACE inhibition, it is uncertain whether the beneficial effect is mediated by interfering with angiotensin II (Ang II) or by modulating other effector systems, for example, bradykinin. METHODS: To assess a potential role of bradykinin, subtotally nephrectomized Sprague-Dawley rats (SNX) received either the ACE inhibitor Ramipril (Rami, 0.2 mg/kg body weight p.o.), the specific B2 bradykinin receptor antagonist Hoe140 (0.2 mg/kg body weight, s.c.), or a combination of both, and were compared to sham-operated controls. To separately assess the effect of Ramipril on development and reversal of structural abnormalities, animals were either treated from the third day after SNX or from the fourth week after SNX onward (0.01 mg/kg body weight, p.o.). RESULTS: Heart and aorta were evaluated by morphometric and stereologic techniques. The weight of the perfused left ventricle, as an index of cardiac hypertrophy, was significantly higher in untreated SNX. While it was significantly lower in animals with early and late Ramipril treatment, the beneficial effect was completely antagonized by Hoe140. The wall-to-lumen ratio of intramyocardial arterioles was significantly higher in untreated SNX compared with controls, but failed to be modified by administration of either Ramipril or Hoe140. In the heart, the intercapillary distance was significantly higher in SNX, but it was not lowered by either early or late Ramipril or Hoe140 treatment. Treatment of SNX with Hoe140 alone, however, resulted in a marked further increase in intercapillary distance. The wall thickness of the aorta was significantly higher in SNX than in controls; early and late Ramipril treatment prevented such increase, and this effect was antagonized by Hoe140. CONCLUSION: These findings illustrate that bradykinin plays an important role for the beneficial effect of Ramipril in preventing (and potentially reversing) abnormal cardiovascular structure in uremic hypertensive rats.     

Value of preoperative diagnostic modalities in patients with recurrent thyroid carcinoma

BACKGROUND: Patients with well-differentiated thyroid cancer (WDTC) regularly have an excellent prognosis. However, tumor recurrence either involving the thyroid bed or the regional lymph nodes, or both, can be associated with significant morbidity and even mortality. The aim of the follow-up after primary surgery is to detect recurrent disease at its earliest stage. We assessed the value of different diagnostic methods in detecting locoregional recurrence in patients with WDTC. METHODS: We prospectively identified 150 patients with WDTC. Of those, 43 (28.7%) presented with recurrent disease. Ultrasonography-guided fine needle biopsy (US-FNB), iodine 131 ((131)I) wholebody scintigraphy, thyroglobulin (Tg) measurement, and fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) were carried out. RESULTS: Ultrasonography detected malignant lesions in 95.3% of the patients. The true positive rate of US-FNB was 95.3%. (131)I scanning had true positive, false negative, and false positive results in 54.2%, 40.0%, and 5.7% of the cases, respectively. In 85.7% of the patients, Tg levels were within pathologic range. Among the 13 patients who underwent FDG-PET, 84.6% showed pathologic uptake indicating malignancy. US and US-FNB provided the highest specificity for detecting recurrence (P <.001). CONCLUSIONS: In patients with WDTC and locoregional recurrence, US and US-FNB are the most sensitive methods in detecting local recurrence or regional lymph node metastases. FDG-PET is valuable in case of negative (131)I scanning results and elevated serum Tg levels. The method has limitations in finding minimal disease.     

The effect of azathioprine (Imuran) on the kinetics of monocytes and macrophages during the normal steady state and an acute inflammatory reaction

The effect of azathioprine on the kinetics of peripheral blood monocytes and peritoneal macrophages was studied in normal mice and in mice in which an inflammatory reaction was provoked. Two dosage levels were used: a high dose of 200mg/kg which is the maximum tolerated daily dose in mice, and low dose of 3 mg/kg which is about equivalent to a nontoxic, immunosuppressive, anti-inflammatory dose in man. The number of peripheral blood monocytes decreases gradually during azathioprine treatment of normal mice, the extent and duration being dependent on the dose and duration of administered over a period of 9 days gives an almost complete reduction, and a low dose (3 mg/kg) given for the same period results in a reduction of about 50%. This effect seems to be reversible, because when treatment is stopped the number of monocytes starts to increase 24-48 hr later. The number of peritoneal macrophages is only affected when a high dose (200 mg/kg) is given over a long period; a low dose has virtually no effect. In mice in which an inflammatory reaction was prevoked in the peritoneal cavity, the normally occurring increase in the numbers of both peripheral blood monocytes and peritoneal macrophages was suppressed, the extent being dependent on the dose of azathioprine administered. Labeling studies with 3H-thymidine indicated that the reduction of peripheral blood monocytes and peritoneal macrophages in the inflammatory exudate is due to a diminished monocyte production.