Search

In this study, colonic biopsy specimens from 87 subjects (37 men and 50 women; mean age 51 +/- 14 years) were investigated by a new method of quantitation morphometric analysis. Subjects were classified in 3 groups: I, control group (25 cases); II, constipation and/or abdominal pain (36 cases); III, diarrhea (26 cases). All biopsy specimens were considered normal by both colonoscopic and microscopic observations. Morphometric analysis was performed with a specialized automated image processor. Complete analysis of 1 biopsy specimen required about 10 minutes. Glandular area showed no difference in the ascending, transverse, and descending colonic sites in the three groups. By contrast, the rectal glandular area was significantly larger than those from the 3 colonic sites in all groups (p less than 0.001). The mean cellular density in the control group was 172.7 +/- 24 nuclei/unit area of lamina propria at all biopsy sites. The cellular densities of groups II and III were significantly increased in the ascending colon as compared with the group I subjects (195.1 +/- 22.8, p less than 0.01 and 198.2 +/- 24.7 p less than 0.001, respectively). The cellular density in group III was significantly increased in the other sites as compared with group I (p less than 0.01). Morphometric analysis does provide a definition of the normal range of the lamina propria cellularity and can identify mild abnormalities in patients in whose both colonoscopy and conventional histologic interpretation have been considered as normal by experienced endoscopists and pathologists. A statistical increase in cellular density in groups of patients with clinical symptoms should be regarded as consistent with the concept of microscopic colitis and detectable by morphometry. Such a method reduces interobserver bias and permits objective comparison of groups.

The effects of renovascular hypertension and its treatment by a converting enzyme inhibitor (perindopril) on the structure and function of large arteries were studied in the Goldblatt 1 clip--2 kidney rat. One month after the surgical operation, the hypertensive animals (n = 24) and the sham operated animals (n = 24) were divided into two groups receiving either 1 mg/kg per day of perindopril or distilled water for four weeks. At the end of treatment, the hemodynamic parameters, including blood pressure and instantaneous blood flow measured by Doppler, were measured in anesthetized rats. The mechanical properties of the carotid artery were studied by in situ measurement of the carotid compliance in response to imposed pressures. Lastly, morphometric parameters of the thoracic aorta, including the thickness of the media, the density of elastin, collagen and nuclei and the area of the nuclei were studied by an automated image analysis system. Hypertension was associated with an increase in the characteristic impedance of the aorta (14,479 +/- 5,171 vs 9,022 +/- 4,071 dyne.sec/cm5; p less than 0.01) and a reduction in systemic arterial compliance (2.41 +/- 0.96 vs 3.92 +/- 1.15 x 10(-3) ml/mmHg; p less than 0.01) or carotid arterial compliance (6.31 +/- 1.85 vs 8.38 +/- 3.14 x 10(-2) mm3/mmHg; p less than 0.05). Treatment with perindopril normalized systolic and diastolic blood pressure and completely inverted the markers of rigidity of the large arteries. Morphometric analysis of the aortic wall allowed these functional modifications to be attributed to structural modifications of the wall. The thickness of the media was increased by hypertension (122.3 +/- 3.7 vs 97.5 +/- 4.4 microns; p less than 0.01). This thickening was attributed to hypertrophy of the smooth muscle cells as evidenced by the increase in the nucleus size (8.58 +/- 1.54 vs 7.38 +/- 0.78 microns 2; p less than 0.01). It was accompanied by an increase in the density of collagen (8.6 +/- 3.6 vs 7.3 +/- 2.4%; p less than 0.01) and a decrease in the density of elastin (31.9 +/- 8.3 vs 38.6 +/- 12.8%; p less than 0.01). Treatment with perindopril normalized the thickness of the media (103.0 +/- 4.8 microns) by reducing cellular hypertrophy. The short duration of treatment did not allow regression of the modifications in the density of the proteins of the interstitial matrix. In conclusion, renovascular hypertension severely alters the functional and structural properties of large arteries. Treatment with perindopril normalizes the properties of the vessel wall.(ABSTRACT TRUNCATED AT 400 WORDS)

We attempted to ascertain the mechanism of portal hypertension and ascites complicating acute hepatitis in 66 patients who underwent transvenous liver biopsy and measurement of hepatic venous pressure gradient. Increase in hepatic venous pressure gradient was related to the severity of acute hepatitis, as indicated by the significant correlation between the values for hepatic venous pressure gradient and serum bilirubin, serum albumin or coagulation factor V, and by its higher value in patients with, than in patients without, encephalopathy. Hepatic venous pressure gradient was higher in patients with, than in patients without, ascites (12.5 +/- 3.4 vs. 8.4 +/- 3.6 mmHg, respectively; p less than 0.001). No ascites was clinically detectable in the patients in whom hepatic venous pressure gradient was below 6 mmHg. We tested the hypothesis that sinusoidal collapse due to liver cell dropout was a major factor in portal hypertension. Semiautomatic determination of the fractional area of sinusoidal collapse on chromotrope-stained sections and automatic measurement of Sirius red-stained collagen fiber density were performed. Hepatic venous pressure gradient significantly correlated with fractional sinusoidal collapse area (r = 0.61, p less than 0.001) and with Sirius red-stained collagen fiber density (r = 0.43, p less than 0.01). We conclude that portal hypertension in the course of acute hepatitis is related to the severity of liver damage and is a major factor in the development of ascites. Portal hypertension is mainly determined by intrahepatic vascular space being reduced by the collapse of sinusoids.

Erythropoietin producing cells were identified in the murine hypoxic kidney by in situ hybridization. The positive cells were peritubular cells, most likely endothelial cells of the cortex and outer medulla. Glomerular and tubular cells were not labelled. In three patients with renal adenocarcinomas associated with polycythemia, a strong Epo message was observed on Northern blot analysis. Using in situ hybridization, a strong labelling was observed in all cases on the tumor cells which are of tubular origin.

Using an automatic image analysis processor we measured the cellular density of the lamina propria and the mean glandular area on biopsies issued from 10 normal patients. The microscopic image was automatically digitalized and filtered. The operator manually traced the perimeter of the mucosal glands. The mean nucleus number for a 32,000 microns2 chorionic area is 177 +/- 24. The mean glandular area is 51.2 +/- 2.9%. This method is fast (2 min by field) and reproducible. It can be proposed for the study of inflammatory conditions on systematic colonic biopsy material.

An automated image analysis system was used to analyze the collagen pattern in picrosirius-stained sections of the left ventricular myocardium from 27 rats: 9 sham-operated animals (controls), 9 animals with one-clip, two-kidney Goldblatt renovascular hypertension (RVH) and 9 animals with an aortocaval fistula (ACF) model of volume overload hypertrophy. The collagen content and fiber thickness were significantly increased in the RVH group as compared to the ACF and sham-operated groups (P less than .001). These parameters were correlated to the left ventricular wall thickness (R = .66; P less than .01). On the other hand, form factors were significantly increased in both treated groups as compared to the controls. These findings indicate that increased collagen formation and increased left ventricular wall thickness probably depend on the type of load and were particularly important when afterload is increased.

In order to investigate the consequences of different types of cardiac hypertrophy on myocardial capillary and fibrosis density in rats we describe here, in the same hearts, the pattern of capillary bed density visualized by fluorescein isothiocyanate dextran (FITC-dextran) and the pattern of fibrosis density as determined by automated image analysis. Pressure overload was induced by clipping one renal artery in rats (one-clip, two-kidney Goldblatt hypertension, RHV). Volume overload was induced by creation of an arteriovenous shunt between the abdominal aorta and the vena cava (aorto-caval fistula model ACF). Animals were sacrified at 1, 3 and 6 months following surgical procedure. Immediately prior to sacrifice, FITC-dextran (MW 150,000) was injected with the animal under ether anesthesia. Five minutes later, cardiac diastolic arrest was induced by the i.v. injection of potassium chloride. The heart was rapidly excised and placed in a formaldehyde solution. The degree of cardiac hypertrophy was calculated after measurement of cardiac weight. Left ventricular wall thickness and cavity area were measured by microscopic methods. Capillary density and geometry were determined by morphometric methods, under ultraviolet light microscopy, using a graphic tablet connected to a microcomputer. The degree of myocardial fibrosis, visualized with Sirius Red, was estimated by the use of automated image analysis using light microscopy. In renovascular hypertension, cardiac hypertrophy was maximum at one month (36%) and persisted through the six months of the study. This increase in cardiac mass was concentric, due to a significant increase in ventricular wall thickness and was associated with a marked increase in fibrosis and a significant decrease in subendocardial capillary density. These effects existed already one month and did not change with time. In the aorto-caval fistula model, cardiac hypertrophy was also maximum at one month (+56%), but this eccentric increase in cardiac mass was associated with no significant change in left ventricular wall thickness, but rather with a significant increase in the surface area of the left ventricular cavity. This volume overload hypertrophy was associated with a decrease in subendocardial capillary density which was negatively correlated with time. In contrast to concentric hypertrophy there was no increase in the fibrosis density compared to the sham-operated groups. Despite the identical degrees of hypertrophy, pressure and volume cardiac overload differed in a significant manner in both left ventricular wall thickness and cavity surface area.(ABSTRACT TRUNCATED AT 400 WORDS)