Human placental alkaline phosphatase in benign and malignant ovarian neoplasia

In benign and malignant ovarian tumor patients, human placental alkaline phosphatase (HPLAP) was determined in serum and extracts from surgical tumor biopsies using a highly specific enzyme-antigen immunoassay based on a mouse monoclonal antibody (E6) to HPLAP. Serum HPLAP levels greater than or equal to 0.1 unit/liter were found in 58% of ovarian cancer patients. Serum carcinoembryonic antigen levels were positive (greater than 5.4 ng/ml) in 17% of these patients. HPLAP was detected in extracts from 13 of the 14 tumors investigated (range, 2.4 to 557 milliunits/g). Only the mixed heterologous Müllerian sarcoma was negative. The highest HPLAP content of normal ovarian tissue was 1.1 milliunits/g. The amount of heat-stable and L-p-bromotetramisole-insensitive alkaline phosphatase was in all cases much higher than the fraction recognized by E6. The neoplastic origin of HPLAP was confirmed immunohistochemically on paraffin sections by an indirect avidin-biotin-peroxidase staining procedure using E6. The staining pattern was compared to the histochemical distribution of total alkaline phosphatase on adjacent sections. A consistency was found between the amount of HPLAP in tissue extracts and its immunohistochemical distribution. In all the tumors, staining for HPLAP was observed mainly on the plasma membranes of carcinoma cells. In 9 of the 10 carcinomas, the histological distribution of HPLAP and also of total alkaline phosphatase was heterogeneous. HPLAP staining, present in one of five normal ovaries, was restricted to germinal inclusion cysts. The present results support the hypothesis that serous ovarian tumors originate from these cysts.     

Thoracic wall involvement by Hodgkin disease and non-Hodgkin lymphoma: CT evaluation

Thoracic computed tomographic (CT) scans of 250 patients with newly diagnosed or recurrent lymphoma revealed thoracic wall involvement in 24 patients (11 with Hodgkin disease, 13 with non-Hodgkin lymphoma). Thoracic wall involvement occurred without contiguous mediastinal or parenchymal involvement in 17 patients. Of these, 13 patients had masses beneath the pectoralis muscles or within the breast, and four had masses arising from the ribs. Five additional patients had mediastinal masses with thymic involvement and parasternal extension through the thoracic wall. Pulmonary parenchymal lymphoma with thoracic wall invasion was noted in the remaining two patients. In five of nine patients receiving radiation therapy, treatment plans were modified by CT demonstration of thoracic wall lymphoma.     

Outpatient management of abnormal smears

OBJECTIVES: To review the results of the first 403 women treated at the Abnormal Smear and Colposcopy Unit with special reference to the utility, efficacy, acceptability and economy of in-office treatment of cervical lesions by large loop or Fischer cone excision. DESIGN: Retrospective chart review of consecutive patients treated following, referral with an abnormal smear or abnormal cervical morphology, between 1 September 1996 and 1 August 2001. SETTING: Inner city private practice. SAMPLE: A total of 403 consecutive General Practitioner referred women. METHODS: Details of referral smear result, colposcopically directed biopsy result, subsequent treatment type and histological result including assessability, number of specimens submitted, complications and follow-up assessment were extracted at chart review. Costs of public hospital inpatient and outpatient care, supplied by the Casemix and Clinical Benchmarking Service, Mater Miseraecordae Public Hospitals (with permission to publish), were compared with Medicare rebates. MAIN OUTCOME MEASURES: A total of 187 women were treated by large loop excision of the transformation zone, and 216 by Fischer cone excision. The number of women who were treated as outpatients under local anaesthetic were 395, while eight patients were treated under general anaesthesia as inpatients. There was poor correlation between referring smear, biopsy and subsequent treatment results. Eight patients had abnormal cytology at follow-up, of whom two have been retreated. Three patients had primary or secondary bleeding requiring treatment and two developed cervical stenosis. Outpatient private practice treatment of women with abnormal smears allows significant savings to the public purse over public or private hospital care. CONCLUSIONS: Outpatient treatment of women with abnormal smears, using the Fischer cone technique, is safe, well accepted, effective and the most cost efficient solution to this public health problem.     

Reduced postischemic macrophage infiltration and interstitial fibrosis in osteopontin knockout mice

BACKGROUND: Osteopontin (OPN) is a phosphoprotein that is up-regulated in several experimental models of renal disease, including ischemia/reperfusion injury. OPN has been described as a macrophage chemoattractant, may serve as a survival factor for tubular cells, and is implicated in the development of tubulointerstitial fibrosis. However, the precise role of this protein in renal pathophysiology remains unclear. METHODS: OPN knockout and wild-type mice were subjected to 30 minutes of warm renal ischemia combined with a contralateral nephrectomy, and sacrificed at six different time points, ranging from 12 hours to seven days after reperfusion. Besides functional and morphological parameters of postischemic acute renal failure (ARF), macrophage infiltration, apoptosis and expression of collagen types I and IV were investigated. RESULTS: Postischemic ARF in OPN knockouts and wild-types showed a similar course and severity, without significant differences in either functional or morphological disease parameters. However, macrophage infiltration was significantly diminished in OPN knockouts after five and seven days, in cortex as well as in the outer stripe of the outer medulla (OSOM). Furthermore, OPN knockout mice showed significantly enhanced apoptosis in the injury phase and significantly less collagen I and IV expression in the regeneration phase of postischemic ARF. CONCLUSIONS: There was no influence of OPN protein on the severity or course of functional impairment or morphological injury in the first seven days after an ischemic insult to the kidney. However, our results demonstrate that OPN favors macrophage recruitment to the postischemic kidney, inhibits apoptosis, and stimulates the development of renal fibrosis after an acute ischemic insult.     

ICAM-1 expression and leukocyte accumulation in inner stripe of outer medulla in early phase of ischemic compared to HgCl2-induced ARF

BACKGROUND: After ischemia/reperfusion (I/R), as well as after toxic insults, there is significant infiltration of leukocytes in the kidney. It is well known that antibodies against adhesion molecules [e.g., intercellular adhesion molecule-1 (ICAM-1)] protect the kidney against acute ischemic injury. In contrast, same antibody treatment did not protect the rat kidney against toxic acute renal failure (ARF) induced by HgCl2. Protection obtained by anti-adhesion treatment in I/R injury is an early phenomenon, since delaying the administration of anti-ICAM-1 for 8 hours did not protect the kidney anymore. The aim of this study was to compare the early ICAM-1 expression and leukocyte accumulation in different zones of ischemic and toxic injury. METHODS: Male Lewis rats were injected with HgCl2 (2 mg/kg, subcutaneously) or uninephrectomized Lewis rats were submitted to 30 degrees C warm ischemia (I/R injury). Rats were sacrificed at 2, 6, 12 and 24 hours. ICAM-1 (1A29) expression in kidney was evaluated morphometrically. Different subsets of leukocytes were stained by immunohistochemistry and counted in cortex, the outer stripe of the outer medulla (OSOM) and the level of the inner stripe of the outer medulla (ISOM). RESULTS: Although the functional and morphologic damage was comparable between the I/R and toxic ARF group, different ICAM-1 expression could be observed early after injury. ICAM-1 expression in the ISOM started already 2 hours after the onset of I/R injury, and was increased after 12 hours in the cortex and after 24 hours in the OSOM. In contrast, during the first 24 hours after injury, ICAM-1 expression in HgCl2-injured kidneys was not different from noninjured kidneys in the ISOM and the cortex, whereas in the OSOM, ICAM-1 expression increased. The number of polymononuclear cells (PMNs) was low in noninjured kidneys and did not increase in time after both I/R injury and after HgCl2-induced ARF. In the ISOM, significant monocyte and T-cell accumulation was observed early after I/R but not after HgCl2. There was no significant T-cell accumulation in the cortex or in the OSOM. CONCLUSION: After HgCl2, almost no leukocyte accumulation and up-regulation of ICAM-1 was observed the first 12 hours after injury. In contrast, very early after I/R injury, increased expression of ICAM-1 goes along with monocyte and T-cell accumulation in the ISOM, endorsing this particular zone as critical in renal I/R injury. These observations contribute to the understanding why anti-ICAM-1 treatment in acute I/R injury is successful, but fails in acute toxic injury induced by HgCl2.     

A 6-year study of cognition and spatial function in the demented and non-demented elderly: the Sydney Older Persons Study

BACKGROUND: Spatial function has been suggested to be disproportionately worse in people with dementia with Lewy bodies (DLB) than other dementia groups, and poor performance on the Mini-Mental State Examination pentagon copying (PC) task has been proposed as adequate for assessing this. We aimed to establish the prevalence of poor PC in the non-demented elderly; determine the validity of the use of PC as a spatial function test, and determine if poor PC is more common in DLB than non-DLB dementias. METHODS: In a population-based sample of 299 participants, 126 were rated as being cognitively normal (clinical rating scale [CDR] = 0), 95 mildly cognitively impaired (CDR = 0.5), and 78 met criteria for dementia, 19 of whom met criteria for probable DLB (pDLB) and 25 with none of the core features of DLB (non-DLB). The accuracy of PC performance was determined across CDR groups, and the relationship of PC to performance on a broad range of cognitive tests was evaluated. The dementia groups were compared cross-sectionally to determine differences in PC and other cognitive test performance, as well as 3 and 6 years earlier to determine cognitive differences at initial stages of cognitive decline. RESULTS: Poor PC was common in the non-demented elderly (39% CDR = 0; 43% CDR = 0.5). In this non-demented group, PC was selectively related to tests of spatial function. Poor PC was not significantly different in the pDLB and non-DLB groups at any assessment time, however it became more prevalent as dementia severity increased. Memory function and verbal fluency were more impaired in the pDLB group in the early stages of the disorder. COMMENT: PC appears to be a good measure of spatial function in the elderly. However, in contrast to other findings of poor spatial skills in DLB when dementia is in the mild to moderate stages, poor PC performance has not been shown to be a good early marker of DLB and its clinical correlates are yet to be determined.     

Vitamin K intake and bone mineral density in women and men

BACKGROUND: Low dietary vitamin K intake has been associated with an increased risk of hip fracture in men and women. Few data exist on the association between dietary vitamin K intake and bone mineral density (BMD). OBJECTIVE: We studied cross-sectional associations between self-reported dietary vitamin K intake and BMD of the hip and spine in men and women aged 29-86 y. DESIGN: BMD was measured at the hip and spine in 1112 men and 1479 women (macro x +/- SD age: 59 +/- 9 y) who participated in the Framingham Heart Study (1996-2000). Dietary and supplemental intakes of vitamin K were assessed with the use of a food-frequency questionnaire. Additional covariates included age, body mass index, smoking status, alcohol use, physical activity score, and menopause status and current estrogen use among the women. RESULTS: Women in the lowest quartile of vitamin K intake (macro x: 70.2 microg/d) had significantly (P < or = 0.005) lower mean (+/- SEM) BMD at the femoral neck (0.854 +/- 0.006 g/cm(2)) and spine (1.140 +/- 0.010 g/cm(2)) than did those in the highest quartile of vitamin K intake (macro x: 309 microg/d): 0.888 +/- 0.006 and 1.190 +/- 0.010 g/cm(2), respectively. These associations remained after potential confounders were controlled for and after stratification by age or supplement use. No significant association was found between dietary vitamin K intake and BMD in men. CONCLUSIONS: Low dietary vitamin K intake was associated with low BMD in women, consistent with previous reports that low dietary vitamin K intake is associated with an increased risk of hip fracture. In contrast, there was no association between dietary vitamin K intake and BMD in men.