Ultrastructure of the early human implantation in vitro

Four hatched human blastocysts obtained after in-vitro fertilizationand development were placed on monolayer cell cultures of humanendometrial epithelium, and subsequently examined by transmissionelectron microscopy. All four blastocysts became adherent tothe monolayer and three implanted and exhibited outgrowth oftheir trophoblastic cells. During implantation the blastocystsdifferentiated into mural and polar trophoblastic cells, andembryonic cells including endodermal cells. The endometrialcells were displaced and stacked into a multilayer at the peripheryof the implantation sites, allowing the trophoblastic cellsto come in contact with the culture dish. The endometrial cellsdisplayed local exo- or endo-cytosis where they contacted thetrophoblastic cells. The trophoblastic cells were not observedto be phagocytosing endometrial cells. These observations suggestthat human blastocysts portray an intrusive type of implantationduring the initial stages.     

Histopathological grading of soft tissue tumours. Prognostic significance in a prospective study of 278 consecutive cases

A consecutive 10-year series of 278 soft tissue sarcomas was prospectively graded, using a system based on the number of mitoses and taking into account parameters such as cellularity, anaplasia, necrosis, and histogenetic type and subtype of tumour. Prognostic factors in relation to metastasis-free survival were studied by uni- and multivariate analysis. Fifty-seven (20.5 per cent) were low-grade tumours, 43 (15.5 per cent) were intermediate, and 178 (64 per cent) were high grade. High-grade tumours were divided into two groups; 80 (29 per cent) grade 3A (= 5-20 mitoses per 10 high power fields (HPF)) and 78 grade 3B (28 per cent) (= more than 20 mitoses/10 HPF); 10 HPF corresponds to 2.5 mm2. Twenty (7.2 per cent) high-grade tumours could not be further subdivided. Grading was found to be the prognostic factor associated with the strongest predictive value. Five-year survival in low-grade and intermediate tumours (95 and 86 percent, respectively) differed significantly (P less than 0.0001) from high grade (50 per cent) and (p = 0.0018) between grade 3A (64 per cent) and grade 3B (41 per cent). Other prognostic indicators of importance in high-grade tumours were age, local recurrence at presentation (primary operation outside the Centre), and localization (superficial vs. deep).     

Colocalization of glutamate and glycine in bipolar cell terminals of the human retina

Human retinae from surgical specimens rapidly fixed in a glutaraldehyde/formaldehyde mixture were subjected to postembedding, immunogold immunocytochemistry of glutamate and glycine, and subsequently analysed in an electron microscope. The two amino acids were visualised in the same tissue sections by the use of two different gold particle sizes. All bipolar cell perikarya and terminals showed significant glutamate labelling with mean gold particle densities 3–4 times higher than those of the retinal, non-neural pigment epithelial and Müller cells. Bipolar cell terminals displayed significantly higher glutamate labelling density than the bipolar cell bodies, as would be expected of glutamatergic neurons. A subpopulation of the glutamate-immunolabelled bipolar cell bodies (18%) and terminals (32%) also exhibited strong glycine labelling (7–8 times that of pigment epithelial and Müller cells). These glutamate-glycine positive terminals established contacts with amacrine cell processes and ganglion cell dendrites and were localised almost exclusively at between 44% and 88% depth of the inner plexiform layer, indicating that they belong to the ON cone bipolar system. This subpopulation of terminals was endowed with significantly higher glycine labelling density than the glycine positive bipolar cell bodies. These results show that human bipolar cell terminals colocalise glutamate and glycine and provide the first direct demonstration of an enrichment of these two amino acids in the same presynaptic element.     

The expression and activity of renal nitric oxide synthase and circulating nitric oxide in polycystic kidney disease rats

Nitric oxide (NO) influences tubular fluid and electrolyte transport, and hence possibly also fluid accumulation in renal cysts. The expression and activity of intrarenal constitutive NO synthase (cNOS) [neuronal NOS, nNOS and endothelial NOS, eNOS] and inducible NOS (iNOS) and plasma nitrite/nitrate (PNOx) concentration were assessed in homozygous Han:SPRD polycystic kidney disease (PKD) rats (cy/cy), heterozygous Han:SPRD PKD rats (cy/+), homozygous normal Han:SPRD littermates (+/+) and Sprague Dawley rats (sd). The results showed: 1) nNOS expression was decreased in proximal tubules and thick ascending limbs of the loop of Henle in cy/cy and cy/+ rats compared to +/+ and sd rats (p<0.05). nNOS was weakly expressed in the epithelium of small cysts and unexpressed in epithelium of large cysts. 2) iNOS expression was increased in proximal tubular epithelial cells in cy/+ rats compared to +/+ rats and sd rats (p<0.01). iNOS expression in cyst epithelium was decreased in cy/+ rats (p<0.05) and absent in cy/cy rats. 3) eNOS expression was similar in the endothelium of intrarenal arteries in all groups. 4) The activity of renal cNOS was decreased in cy/cy and cy/+ rats; the activity of iNOS was decreased only in cy/cy rats, with no significant difference among the other three groups. 5) PNOx concentration was higher in cy/cy rats than in the other three groups, and correlated positively with plasma creatinine and urea. In conclusion, NOS expression and activity decreased as cysts developed, suggesting that NO downregulation is involved in the pathogenesis of PKD.     

Marfan syndrome: Evolving organ manifestations—A 10‐year follow‐up study

The age‐dependent penetrance of organ manifestations in Marfan syndrome (MFS) is not known. The aims of this follow‐up study were to explore how clinical features change over a 10‐year period in the same Norwegian MFS cohort. In 2003–2004, we investigated 105 adults for all manifestations in the 1996 Ghent nosology. Ten years later, we performed follow‐up investigations of the survivors (n = 48) who consented. Forty‐six fulfilled the revised Ghent criteria. Median age: females 51 years, range 32–80 years; males 45 years, range 30–67 years. New aortic root dilatation was detected in patients up to 70 years. Ascending aortic pathology was diagnosed in 93 versus 72% at baseline. Sixty‐five percent had undergone aortic surgery compared to 39% at baseline. Pulmonary trunk mean diameter had increased significantly compared to baseline. From inclusion to follow‐up, two patients (three eyes) developed ectopia lentis, four developed dural ectasia, four developed scoliosis, three developed incisional or recurrent herniae, and 14 developed hindfoot deformity. No changes were found regarding protrusio acetabuli, spontaneous pneumothorax, or striae atrophicae. The study confirms that knowledge of incidence and progression of organ manifestations throughout life is important for diagnosis, treatment, and follow‐up of patients with verified or suspected MFS.     

The Cerebral Circulation in the Elderly: The Influence of Age, Vascular Disease, and Antihypertensive Treatment

Cerebral blood flow (CBF) and cerebral metabolic activity tend to decrease in old age. The effect of age per se on the regulation of CBF is not readily separated from the effect of age-associated diseases such as atherosclerosis, multi-infarct dementia, and diabetes mellitus, which may lead to an impairment of CBF autoregulation. Stroke may be prevented effectively by antihypertensive treatment in otherwise healthy elderly patients, but care should be taken to prevent overtreatment with consequent cerebral ischemia. The risk of this may be especially great in elderly patients with hypertension who have postural hypotension.     

Immunohistological expression of HIF‐1α, GLUT‐1, Bcl‐2 and Ki‐67 in consecutive biopsies during chemoradiotherapy in patients with rectal cancer

The aim of this study was to describe the dynamics of HIF‐1α, GLUT‐1, Bcl‐2 and Ki‐67 during chemoradiotherapy (CRT) of rectal cancer, and to investigate the fluctuation of these biomarkers in relation to pathological response to CRT. The study included 86 patients with rectal adenocarcinoma receiving preoperative CRT (>50.4 Gy and Uracil/Tegafur). Immunohistological expressions of HIF‐1α, GLUT‐1, Bcl‐2 and Ki‐67 were investigated in biopsies taken before treatment, after 2, 4 and 6 weeks of CRT and in specimens from the operation. Decreasing expressions of HIF‐1α, Bcl‐2 and Ki‐67 were observed during CRT, whereas GLUT‐1 overall was unchanged. No significant changes of the markers were observed in the interval between CRT and surgery. A significant association was observed between the presence of residual carcinoma after 6 weeks of treatment and pathological response to CRT, but no association was seen between the fluctuations of any of the markers and response to CRT. This unique material containing specimens before, after and during CRT for rectal cancer demonstrated biological dynamics in HIF‐1α, Bcl‐2 and Ki‐67, but not GLUT‐1, expression during CRT, and a significant association was seen between the presence of residual carcinoma after 6 weeks of treatment and pathological response to CRT.     

Omeprazole 20 mg three days a week and 10 mg daily in prevention of duodenal ulcer relapse. Double-blind comparative trial

In a double-blind, parallel-group clinical trial of 195 patients with duodenal ulcers who after a short-term study had relief of pain and healed ulcers proved endoscopically, 65 were randomized to receive 20 mg omeprazole 3 days a week (once in the morning from Friday to Sunday), 64 to receive 10 mg omeprazole once daily in the morning, and 66 to receive placebo for up to 6 months. The patients underwent repeat endoscopy with biopsy of the gastric fundic mucosa (qualitative assessment of argyrophilic cell population), assessment of symptoms, and laboratory screening with measurement of basal serum gastrin concentrations at 3 and 6 months or more often if indicated by recurrence of symptoms. At 3 months, endoscopically proved ulcer relapse occurred in 16% receiving 20 mg omeprazole 3 days a week; 21% receiving 10 mg omeprazole daily; and 50% receiving placebo. At 6 months, corresponding rates were 23%, 27%, and 67% with 95% confidence intervals of difference between the placebo group and omeprazole groups of 28%-60% and 24%-56% (P less than 0.00001), respectively, and between omeprazole groups of -19%-11% (NS). No major clinical or laboratory side effects were noted. Thus both omeprazole regimens are effective and safe in preventing duodenal ulcer relapse.