Blood pressure and cardiac changes during signalled and unsignalled avoidance in dogs.

Alterations in blood pressure (BP) during two aversive behavioral tasks were studied in five chronically-prepared dogs. During a signalled-avoidance task, BP levels were not altered, although heart rate (HR) increased. While propranolol (0.3 mg/kg, IA) led to slight increases in resting pressure, and phenoxybenzamine (1.0 mg/kg) reductions, the tachycardia at avoidance onset was not affected. Exposure to an unsignalled-avoidance task led to elevated diastolic BP levels during a preavoidance period and to increases in systolic BP, HR and aortic dP/dt at the inception of the avoidance session. Again, neither drug affected the tachycardia during avoidance, but both agents precluded BP and aortic dP/dt increases. Patterns of intercorrelations among cardiovascular variables were similar for both tasks, and suggested that the basis of the BP maintenance shifted from vasomotor to cardiac control during the avoidance periods. The differential cardiovascular adjustments during these tasks could not be accounted for in terms of differences in response rate. Rather, the critical variable seemed to be the amount of feedback the animal received for responding.

Immunohistochemical detection of cell-cycle associated markers on paraffin embedded and formalin fixed needle biopsies of prostate cancer: correlation of p120 protein expression with AgNOR, PCNA/cyclin, Ki-67/MIB1 proliferation-scores and Gleason gradings.

Paraffin embedded and formalin fixed needle biopsies of prostate cancer (PC) were used to immunocytochemically detect the p120 nucleolar protein in relation to the Gleason histological gradings (GHG), the labelling indices of proliferating nuclear immunocytochemical markers (PCNA/Cyclin, Ki-67/MIB1) and the argyrophilic nucleolar region (AgNOR) rate. The twenty-six cases of PC (6 from large histological samples and 20 from needle biopsies) were equally distributed into low (< or = 6) or high (> or = 7) GHG groups. The p120 nucleolar protein immunocytochemical reaction was randomly expressed in large histological sections but uniformly distributed without gaps in needle biopsy sections. Only on the latter were quantitative values of PCNA/Cyclin (23.2 in low and 45.3 in high GHG), Ki-67/MIB1 (13.8 in low and 43.3 in high GHG) and AgNOR (5.0 in low and 7.5 in high GHG) related to those of p120 nucleolar protein (0.8 in low and 3.8 in high GHG). The values of all these cell cycle markers increased from low to high GHG of PC, all four reaching high statistical significance between the two groups (ANOVA-two tailed p < 0.0001). The PCNA/Cyclin index showed a higher positivity than the Ki-67/MIB1 index in PC with low GHG but not in PC with high GHG. In conclusion, paraffin embedded and formalin fixed PC needle biopsies exhibit a higher diagnostic PCNA/Cyclin than Ki-67/MIB1 index for cases presenting differentiated features, whereas p120 nucleolar protein detection seems to be a suitable marker of poorer outcome of PC.

The ability of PiCCO versus LiDCO variables to detect changes in cardiac index: a prospective clinical study.

BACKGROUND: Both PiCCO and LiDCO can provide dynamic preload parameters, pulse pressure variation (PPV) and stroke volume variation (SVV). The PiCCO device also provides a measure of intrathoracic blood volume index (ITBVI). We investigated the agreement between SVV and PPV, as well as the reliability of LiDCO- and PiCCO-measured SVV, PPV and ITBVI, in detecting fluid responsiveness before and after fluid challenge (FC). METHODS: We performed a prospective clinical study in University Hospital ICU. Nine adult ICU patients with cardiovascular instability were enrolled in the study. All patients were sedated and mechanically ventilated with intermittent positive pressure ventilation. The PiCCO and LiDCO systems were both connected to each patient. The PiCCO pulse waveform system was joined by a 5-French (Fr) thermistor-tipped arterial catheter inserted into the femoral artery. LiDCO measurements were performed through radial artery pulse contour analysis. Fluid challenge was performed using a rapid infusion of 7 mL/kg of 6% hydroxyethylstarch over 30 min. RESULTS: Measurements of CI, ITBVI, SVV, and PVV were made using both techniques before and after FC. Pre-FC cardiac index (CI) measurements were similar with both devices, although the reading was higher after FC with the PiCCO device (P<0.001). The correlation coefficient between PiCCO-CI and LiDCO-CI was 0.85 (95% CI: 0.69 to 0.93; P<0.001); for P-PPV and L-PPV, it was 0.74 (95% CI: 0.49 to 0.88; P<0.001). Only ITBV had a significant correlation with LiDCO-CI or PiCCO-CI. CONCLUSION: We found a narrow bias but less accurate precision in cardiac index values measured by a radial artery-site LiDCO catheter and a femoral artery-site PiCCO catheter, with poor agreement between radial and femoral-derived SVV and PPV measurements. ITBVI proved to be the best predictor of fluid responsiveness. The SVV does not seem to be reliable for preload optimization in ICU patients.

Corticotropin regulates transsynaptically the activity of septo-hippocampal cholinergic neurones.

The activity of septo-hippocampal neurones is affected by the action on cholinergic perikarya in the septum of a variety of putative neurotransmitters, including substance P and beta-endorphin. (The latter is released in the septal region from neurones which originate in the medial basal hypothalamus.) It has also been reported that two other neuropeptides, corticotropin (ACTH1-24) and alpha-melanotropin (alpha-MSH), affect acetylcholine turnover in septo-hippocampal neurones in a manner that is not blocked by transection of the afferents to the hippocampus, from which it has been inferred that the neurotransmitters act directly on the hippocampus. We now describe experiments with corticotropin which show that the effect is rather the influence on septo-hippocampal cholinergic neurones of peptidergic neurones within the septum.

Septohippocampal cholinergic neurons are regulated trans-synaptically by endorphin and corticotropin neuropeptides.

The content of acetylcholine (ACh) in nerve terminals or the dorsal hippocampus was examined after intraventricular, intraseptal, or intrahippocampal administration of a variety of endorphin/corticotropin neuropeptides. beta-Lipotropin, alpha-endorphin, gamma-endorphin, alpha-melanotropin, beta-melanotropin, adrenocorticotropin-1-39 (ACTH1-39), and ACTH4-10 (1, 3, 10, or 30 micrograms each) did not affect levels of ACh in the hippocampus 30 min after injection into the lateral ventricle. beta-Endorphin, administered intraventricularly (1, 3, 10, or 30 micrograms) or intraseptally (1 microgram), increased levels of ACh, while ACTH1-24, injected similarly, decreased levels of the neurotransmitter. ACh concentrations remained unchanged after direct application of beta-endorphin or ACTH1-24 (1, 3, 10, of 30 micrograms each) into Ammon's horn. Acute unilateral transection of the fimbria/superior fornix resulted in a time-related decrease in hippocampal ACh concentrations. Levels of ACh did not change 1 hr after transection; however, concentrations of hippocampal ACh decreased significantly 1 d or 1 week after deafferentation. ACh levels in the contralateral hippocampus remained unaffected at all times tested. Fimbrial transection blocked fully both endorphin- and corticotropin-induced changes in hippocampal ACh after the neuropeptides were injected into the lateral ventricle or the septal region. Naloxone, which, after subcutaneous (1 mg/kg) or intraventricular (100 micrograms) injection alone, failed to change levels of hippocampal ACh, antagonized the effects of intraventricular or intraseptal beta-endorphin or ACTH1-24 or hippocampal ACh levels. The results suggest a site of endorphin/corticotropin receptor interaction at the level of cholinergic cell bodies in the septal region for regulating the activity of septohippocampal cholinergic neurons.

Experimental congestive splenomegaly: histological observations in the rat.

In course of experimental pre-hepatic portal hypertension in the rat, the most important histological alterations in the spleen, are represented by pooling of blood in the red pulp, activation of the macrophagic system, with hyperplasia of the histiocytes, increase of reticular fibers and of subcapsular myo-fibroblasts, and finally by evolution towards a diffuse fibrosis all over the parenchyma.

Immunoreactive dynorphin in mammalian spinal cord and dorsal root ganglia.

The distribution of immunoreactive dynorphin (ir-dynorphin) has been determined in dorsal and ventral aspects of spinal cord and in dorsal root ganglia of rabbit and rat. Concentrations are highest in dorsal root, with intermediate levels in ventral cord and low levels in dorsal root ganglia of both species. Levels of ir-dynorphin are relatively uniform over examined segments (vertebrae C2-S3) of rabbit spinal cord and dorsal root ganglia. Gel permeation chromatography of extracts from rabbit dorsal and ventral spinal cord and dorsal root ganglia revealed at least three immunoreactive components of differing molecular size in all three structures. Multiple unilateral or bilateral dorsal rhizotomy (vertebrae C5-T1) in rat did not affect levels of ir-dynorphin in spinal cord. As reported [Goldstein, A. & Ghazarossian, V. E. (1980) Proc. Natl. Acad. Sci. USA 77, 6207-6210], midthoracic spinal transection was without effect. Within the spinal cord, the neuropeptide appears, most probably, to be contained in short-axoned neurons. We surmise that this potent opioid peptide may participate in the processing of sensory information in spinal cord.

Proliferating cell nuclear antigen/cyclin in incidental carcinoma of the prostate.

Monoclonal antibody to proliferating cell nuclear antigen (PCNA) has been used to identify the growth fraction in ten cases of benign prostatic hyperplasia (BPH), in 20 prostatic microcarcinomas (PMC) and in 30 cases of infiltrating prostatic carcinoma (PC). Ten year follow-up was available on all cases by means of clinical, serological, radiological and echographic examinations. The percentage of PCNA-staining nuclei was independently counted by two observers. Statistical analysis showed significant differences between PCNA/cyclin score of BPH and PMC without recurrences with respect to those of PMC with progression and of PC. PCNA immunostaining may represent a reliable method for assessing cellular proliferative activity. It may be used as a more powerful diagnostic hallmark of PMC than patterns of non-malignant microglandular proliferation and is also a useful additional test for assigning histological grades to PMC and PC. Statistical analysis indicated that PCNA/cyclin index was an independent significant prognostic indicator of predicting malignant progression (P < or = 0.01) and survival rates (P < or = 0.05) of PC and PMC (> 5 mm diameter).

Experimental ischemic liver injury and regeneration over 3 months: histological observations in the rat.

Liver histopathology of segmental portal ischemia occurring over a long-term period has not been previously described. For these reasons histological changes in the rat liver were studied from 1 h to up to 90 days after a left lateral and middle segmental portal obstruction. Within 3 h, the hepatocytes showed glycogen depletion in Rappaport zones 1 and 2 and pericentral and central lobular congestion of sinusoids and veins, whereas within 3 days, vein thrombosis appeared in the center of the lobule and liver necrosis was observed in Rappaport zones 2 or 3 or both, followed by restitutio ad integrum of the liver lobule morphology after 20-40 days. These results can be explained in light of two conditions occurring in the rat liver: (i) the peculiar low sensitivity of the liver to O2 debit and the protective or vasoactive effects used during hypoxia; and (ii) the sinusoidal network as a collateral source of the hepatic vascular system. Therefore, morphological assessment of this arteriolar and sinusoidal system, implicated in assuring efficient collateral blood supply in the rat liver with portal ischemia, is essential for understanding the mechanisms behind a natural and timely repair of ischemic injuries in the human liver.

Experimental acute infectious pancreatitis in rats: histological observations.

Microbic contamination has been shown to be a secondary pathogenetic factor in different models of acute pancreatitis. In this paper, we developed an experimental bacterial model of necrotizing acute pancreatitis (NAP). Forty rats were treated by direct inoculation of a suspension of a clinically isolated strain of Escherichia coli, with three different single 0.33 ml injections, into the head, body and tail of the pancreas. Twenty five rats were sham operated and injected with saline. All animals were sacrificed at 48 hours, 4, 6, and 12 days. This experimental model appeared easy to execute without evidence of mortality. Histomorphologically, haemorrhagic NAP was observed, with its final recovery and minimal residual and focal fibrosis of the gland. As reported in the literature, our data underline the relevance of the bacterial component on pathogenesis of NAP, especially as an aggravating factor.

[AIDS splenomegaly and related iron problems]. / Splenomegalia da AIDS e problematiche siderotiche connesse.

Spleens collected from 85 consecutive autopsies of AIDS patients (mean age 37 years) were studied. Splenomegaly, observed in 59 cases (69.4%), does not statistically correlate with life style and blood transfusions. Eleven very large spleens (over 890 g) were associated with opportunistic infections (i.e.: mycobacteria, true fungi and rochalimaea). The histological pattern was characterized by marked lymphoid depletion of the white pulp and--in 67 cases (89.4%)--packing of the pulp cords by macrophages engulfed of brown pigment which was strongly positive to the Perls reaction for ferric iron. The contemporary presence of Perls positive and p24 immunoreactive material was diffusely observed in the cytoplasm of splenic macrophages, also positive to the alkaline tetrazolium reaction. The same was observed in the cytoplasm of monocytes/macrophages of lung and brain (in 5 out of 5 patients with splenomegaly > 600 g, randomly selected). We believe that our findings deal with the formation of a haemoglobin--p24 complex and are in keeping with recent data which suggest the formation of disulphide bonds between viral proteins and haemoglobin.

Experimental acute hepatic vein occlusion: histological observations in the rat.

The histological consequences of hepatic venous outflow obstruction were studied in the rat. Circulatory changes as venous congestion and interstitial fluid accumulation are followed by signs of cellular damage progressing till hemorrhagic infiltration and focal necrosis. These are quite completely reversible in a period of 15 days.

[Mixed neoplasia of the stomach: description of a case of tubular adenoma combined with carcinoid]. / Neoplasie combinate dello stomaco: descrizione di un caso di adenoma tubulare combinato con carcinoide.

We report about a gastric polyp that was a combination of tubular adenoma and carcinoid. The patient, a 76 year-old male, presented with 1 cm sessile polyp, located in the gastric body, that was a combination of a tubular adenoma with moderate dysplasia and a small carcinoid. Immunohistochemically, the latter component was positive for chromogranin and synaptophysin. The patient is alive and well 10 months after endoscopical polypectomy.