Apolipoprotein E allelotype is associated with neuropathological findings in Alzheimer's disease.

In a consecutive hospital-based autopsy series, we examined the relationship between apolipoprotein E (apoE) and Alzheimer's disease (AD) and investigated the clinicopathological relationship in AD. The study population included 99 patients (mean age 81 years) with AD-related neuropathological findings at death, of whom 83 were diagnosed with AD according to the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) classification, and a control group of patients without neurodegenerative disease (n = 1429). The patients were apoE genotyped and the density of ß-amyloid senile plaques, neuritic plaques and neurofibrillary tangles was estimated in the cortex and hippocampus. The utility of immunohistochemical staining using an antibody directed against apoE4 in paraffin-embedded tissue was also evaluated. Among patients with "definite AD" according to CERAD, 65 % were ε4 carriers, compared to 32 % among controls (p < 0.001). The risk of ε4 carriers to develop AD was higher (odds ratio = 4.65, p = 0.001) than for non-ε4 carriers. The amount of ß-amyloid deposition and neurofibrillary pathology differed significantly (p < 0.01) between the genotypes, with increasing densities from ε2 carriers to homozygous ε4 carriers. The effect of ε4 on the presence of clinical symptoms was attenuated and non-significant after adjusting for AD-related neuropathological findings. There was an association between these findings and the presence of clinical symptoms of AD, with neurofibrillary tangles separating patients with and without symptoms of AD markedly better than ß-amyloid. In addition, we found a strong relationship between genotype and immunohistochemical apoE4-staining intensity. In conclusion, this Scandinavian autopsy study shows that the apoE polymorphism is associated with the probability of AD and influences the deposition of ß-amyloid and neurofibrillary pathology. Our findings suggest that the association between apoE and clinical manifestations of AD is mediated mainly through the neuropathological features of AD. Further, we found a relationship between AD-related findings and clinical symptoms of AD with neurofibrillary tangles associating most strongly with clinical symptoms. Finally, immunohistochemical staining in brain specimens is useful for determining ε4- or non-ε4-carrier status.

Postmortem heart weight: relation to body size and effects of cardiovascular disease and cancer.

BACKGROUND: Gender, body weight, and cardiovascular disease (CVD) are all variables known to influence human heart weight. The impact of cancer is less studied, and the influence of age is not unequivocal. We aimed to describe the relationship between body size and heart weight in a large autopsy cohort and to compare heart weight in patients with cancer, CVD, and other diseases. METHODS AND RESULTS: Registered information, including cause of death, evidence of cancer and/or CVD, heart weight, body weight, and height, was extracted from the autopsy reports of 1410 persons (805 men, mean age 66.5 years and 605 women, mean age 70.6 years). The study population was divided in four groups according to cause of death; cancer (n=349), CVD (n=470), mixed group who died from cancer and CVD and/or lung disease (n=263), and a reference group with patients who did not die from any of these conditions (n=328). In this last group, heart weight correlated only slightly better with body surface area than body weight, and nomograms based on body weight are presented. Compared to the reference group (mean heart weight: 426 g and 351 g in men and women, respectively), heart weight was significantly lower (men: P<.05, women: P<.001) in cancer patients (men: 392 g, women: 309 g) and higher (P<.001) in patients who died from CVD (men: 550 g, women: 430 g). Similar results were obtained in linear regression models adjusted for body weight and age. Among CVD, heart valve disease had the greatest impact on heart weight, followed by old myocardial infarction, coronary atherosclerosis, and hypertension. Absolute heart weight decreased with age, but we demonstrated an increase relative to body weight. CONCLUSION: The weight of the human heart is influenced by various disease processes, in addition to body weight, gender, and age. While the most prevalent types of CVD are associated with increased heart weight, patients who die from cancer have lower average heart weight than other patient groups. The latter finding, however, is diminished when adjusting for body weight. SUMMARY: The present study demonstrates that the weight of the human heart is influenced by various disease processes like cancer and CVD, in addition to body weight, gender and, possibly, age.

Combined analysis of vascular invasion, grade, HER2 and Ki67 expression identifies early breast cancer patients with questionable benefit of systemic adjuvant therapy.

INTRODUCTION: Over-treatment of low-risk early breast cancer patients with adjuvant systemic therapies is an important clinical challenge. Better techniques are required which can be used to distinguish between the large group of patients with no residual disease after surgery and consequently no benefit of adjuvant treatment, from the smaller group with high relapse risk. A better integration of available prognostic factors might contribute to improved prediction of clinical outcome. MATERIAL AND METHODS: The current study included 346 unselected pT1pN0 patients who did not receive adjuvant systemic treatment. In Norway, no patients with this stage were recommended systemic treatment at the time of the study (1995-1998). Histological type, tumour size, grade, vascular invasion (VI), hormone receptor (HR) status, HER2 and Ki67 (cut-off 10%) were analysed. Median follow-up was 86 months for relapse and 101 months for death. RESULTS: Thirty-eight patients experienced relapse, 31 with distant metastasis. Twenty-one patients died of breast cancer. In univariate analysis grade, HER2, HR, VI and Ki67 had impact on clinical outcome (p < 0.005, log rank). In multivariate analysis, only grade 1-2 vs. grade 3, HER2, VI, and Ki67 status were significant for disease free survival, distant disease free survival, and/or breast cancer specific survival. These factors were used in combination, to separate patients into groups based on the number of unfavourable factors present [combined prognostic score (CPS) 0-4]. Close to 2/3 of the patients (61.4%) had no unfavourable factor (CPS0), whilst 18.4% had CPS ≥ 2. Only 3.6% of those with CPS0 developed metastasis (p < 0.001). The outcome was clearly worse for patients with CPS ≥ 2 (p < 0.001), systemic relapse was detected in approximately 40%. CONCLUSIONS: This study indicates that the combined use of grade, VI, HER2 and Ki67 identifies a subgroup of breast cancer patients with a relapse risk that may question the benefit of adjuvant systemic therapy.

The apolipoprotein E polymorphism and cardiovascular diseases--an autopsy study.

BACKGROUND: Numerous studies have addressed the association between the apolipoprotein E polymorphism and cardiovascular disease, but only a few reports are based on findings at autopsy. In the present retrospective study, we have used autopsy findings from a general hospital population to further investigate this issue. METHODS AND RESULTS: We collected information from 1522 consecutive autopsy reports (886 men, mean age 65.7 years; 636 women, mean age 69.7 years) conducted at Oslo University Hospital, Norway, in the period from 1996 to 2000. Cause of death and signs related to cardiovascular disease including the degree of atherosclerosis in the aorta and the coronary arteries, signs of myocardial infarction, heart weight, and signs of cerebrovascular disease were recorded. The patients were genotyped, and the apolipoprotein E allele frequencies (ɛ2, 8.0%; ɛ3, 72.6%; and ɛ4, 19.4%) were not statistically different from a group of healthy controls. Approximately 35% of the patients died from a cardiovascular disease. Genotypes differed significantly (P<.05), with more ɛ4-carriers (34.3% vs. 29.6%) and fewer ɛ2-carriers (11.8% vs. 13.9%) among patients who died from cardiovascular disease compared to those who died from other causes. A similar distribution of genotypes was seen in patients recorded with myocardial infarction or cerebrovascular disease. There was an association between the presence of ɛ4 and atherosclerosis in the aorta and coronary arteries, but this did not reach statistical significance. Among patients with signs of coronary heart disease, standardized heart weights were significantly higher in ɛ2-carriers compared to ɛ4-carriers. CONCLUSION: The present autopsy study suggests that the risk of developing and dying from cardiovascular disease, including coronary heart disease and cerebrovascular disease, is influenced by the apolipoprotein E polymorphism.

Post-traumatic inclusion cysts of the iris: a longterm prospective case series.

PURPOSE: Post-traumatic cysts of the iris pose a diagnostic and therapeutic challenge for ophthalmic surgeons. This prospective case series highlights the clinical spectrum and longterm outcomes of different modes of treatment in these cases. METHODS: Eleven cases of post-traumatic iris inclusion cysts, treated with Nd:YAG laser and/or surgical excision were evaluated prospectively over periods ranging from 6 months to 3 years. Ultrasound biomicroscopy features and postoperative outcomes in each were evaluated. RESULTS: Laser iridotomy of the cyst offers a non-invasive method of therapy in these cases but has a high rate of recurrence. The outcomes in most cases were poor, with worse results and more complications encountered in younger age groups. CONCLUSIONS: Iris inclusion cysts have overall poor surgical outcomes as the result of the extensive proliferation of epithelial cells, which may explain why the condition takes a rapid course in younger patients and why severe complications are encountered postoperatively in this age group.

Endobronchial pulmonary nocardiosis.

In recent years, the reported incidence of nocardiosis, a localized or disseminated infection caused by Nocardia, has been increasing. This increase can be attributed to the improvements in diagnostic capabilities and the higher clinical index of suspicion, as well as the increased prevalence of immunosuppressed patients. We report a case of pulmonary nocardiosis in a healthy young female who presented with cough and hemoptysis, which persisted even after empiric treatment for pulmonary tuberculosis. CT scan of her chest showed infiltrates in the right upper, middle and lower lobes with pleural effusion. Bronchoscopy revealed a friable endobronchial mass. Special stains confirmed the diagnosis of nocardiosis. The patient's symptoms and clinical findings improved with trimethoprim-sulfamethoxazole. To the best of our knowledge, this is the fourth case of this illness presenting as endobronchial mass reported in the literature. Pulmonary nocardiosis should be considered in the differential diagnosis of hemoptysis, even in immunocompetent patients.

Atypical presentations of orbital cysticercosis.

We describe three patients with orbital cysticercosis who presented with atypical clinical or radiologic features previously unreported. All three patients had a cyst with a scolex on imaging studies. After 6 weeks of treatment, all three had almost complete resolution of their features.

Role of prophylactic scleral buckling in the management of retained intraocular foreign bodies.

PURPOSE: To evaluate the role of prophylactic scleral buckling procedure with pars plana vitrectomy for the removal of retained intraocular foreign bodies (RIOFB) in the prevention of postoperative retinal detachment. METHODS: In a prospective, clinical, controlled study, 28 patients with RIOFB without retinal detachment were randomly divided into two groups of 15 (group I) and 13 (group II) patients. All patients underwent a standard three-port pars plana vitrectomy with foreign body removal. In addition to this standard procedure, patients assigned to group I had a 360 degrees encircling scleral buckle placed at the time of surgery. Group II patients did not have any scleral buckling. All patients were followed up for an average period of 11.8 months. Both groups were comparable with respect to age, sex, duration of injury, nature of injury, and site, size and type of RIOFB. RESULTS: The retinal detachment rate was found to be 6.6% in group I and 30.8% in group II (P = 0.24). Prophylactic scleral buckling reduced the risk of retinal detachment by 24% but this was not found to be statistically significant. CONCLUSION: Prophylactic scleral buckle placement with pars plana vitreous surgery for RIOFB may reduce the risk of late onset retinal detachment. A larger study would seem warranted.

Pars plana vitrectomy with or without silicone oil endotamponade in post-traumatic endophthalmitis.

BACKGROUND: Results of core vitrectomy in post-traumatic endophthalmitis are poor. Our initial results of complete vitrectomy with primary silicone oil endotamponade were promising. A comparative study of this procedure with conventional core vitrectomy was therefore carried out. METHODS: A prospective randomized controlled study of 24 consecutive cases of post-traumatic endophthalmitis was conducted. Patients were randomized into two groups in the absence of clinical improvement after primary tap and treatment with intravitreal vancomycin and amikacin: group 1 consisted of patients who underwent core vitrectomy alone, group 2 of patients who underwent complete vitrectomy with silicone oil endotamponade. All patients included in the study received intravenous antibiotics and underwent lensectomy. Patients were followed up 1, 2, 4 and 12 weeks postoperatively. In all patients of group 2, silicone oil was removed 6 weeks after primary surgery. The mean duration of follow-up was 112+/-55 days. RESULTS: Vision of 20/400 or better was obtained in 58.33% of cases (14/24). Visual acuity of only one patient in group 1 was >or=20/200, compared with that of 58.3% of patients (7/12) in group 2 ( P=0.02). Intra-operative retinal breaks were found in 50% (6/12) of the patients belonging to group 1, but did not affect the final visual outcome. In group 1, 33.33% (4/12) developed rhegmatogenous retinal detachment in the immediate post-operative period. Only one of these patients had useful final visual outcome after resurgery. CONCLUSION: Complete vitrectomy with primary silicone oil endotamponade is a useful treatment modality which improves the anatomical and functional results in post-traumatic endophthalmitis.