Spontaneous occurrence of atypical hyperplasia and adenocarcinoma of the uterus in androgen-sterilized SD rats.

In SD female rats sterilized by a single injection of testosterone propionate at 2 days after birth, the spontaneous occurrence of atypical hyperplasia and adenocarcinoma of the uterus was observed for a fairly long period (greater than 2 yr). Two atypical hyperplasias and 2 adenocarcinomas were detected in 25 androgen-sterilized rats (ASR) after 500 days of age; in contrast, in 111 normal control rats no abnormal uterine proliferation was detected during a 750-day observation period. These results indicate that a persistence of both hormone imbalances and dysfunctional uteri in ASR induces abnormal uterine proliferation at a late age.

Depressor systems contribute to hypertension induced by glucocorticoid excess in dogs.

OBJECTIVE: The aim of this study was to investigate the role of depressor systems in glucocorticoid-induced hypertension. METHODS: The serial changes in cardiorenal hemodynamics, urinary excretions of kallikrein and prostaglandins (PGE2 and the prostacyclin derivative 6-keto-PGF1 alpha) before, and during the administration of both low and high doses of dexamethasone (9 alpha-fluoro-16 alpha-methylprednisolone) and after the cessation of dexamethasone were examined in conscious trained dogs. In addition, pressor responses to prostaglandin, bradykinin, bradykinin antagonist and indomethacin were studied during the administration of dexamethasone. RESULTS: High-dose dexamethasone induced a significant elevation in mean arterial pressure (MAP) that was accompanied by a significant reduction in the urinary excretion of kallikrein, PGE2 and 6-keto-PGF1 alpha. In contrast, low-dose dexamethasone treatment had no significant effect upon MAP but induced a transient elevation in the urinary excretion of kallikrein, PGE2 and 6-keto-PGF1 alpha. Furthermore, additional oral administration of indomethacin produced a significant elevation in MAP in dogs treated with low-dose dexamethasone; but did not affect the hemodynamics of animals with high-dose dexamethasone. Whilst i.v. administration of either bradykinin or prostacyclin induced a significant reduction in MAP in high-dose but not low-dose dexamethasone-treated dogs, administration of a competitive bradykinin antagonist, D-Arg-[Hyp3, Thi5,8, D-Phe7]-bradykinin induced a significant elevation in MAP in low-dose but not high-dose dexamethasone-treated dogs. CONCLUSION: Depressor systems play an important role in regulation of blood pressure in glucocorticoid-treated dogs.

Central nervous system mediates an antihypertensive property in glucocorticoid hypertension in dogs.

OBJECTIVE: To determine whether the central nervous system has a pressor or a depressor role in glucocorticoid-induced hypertension. METHODS: Intracerebroventricular dexamethasone or its receptor antagonist, RU 38486, was administered in 20 trained conscious dogs. In addition, intracerebroventricular RU 38486 was administered in dogs treated with oral dexamethasone. RESULTS: Intracerebroventricular dexamethasone induced a dose-related reduction in blood pressure accompanied by decreased heart rate and cardiac output. In contrast, intracerebroventricular RU 38486 caused a slight but not significant elevation in blood pressure. Total peripheral resistance showed no significant change throughout the treatment with dexamethasone or RU 38486. In contrast, oral dexamethasone caused significant elevation of blood pressure associated with increased total peripheral resistance and reduced heart rate. In hypertensive dogs treated with oral dexamethasone, intracerebroventricular RU 38486 elicited a more severe form of hypertension accompanied by an attenuation of the heart rate and a reduction in cardiac output. Intracerebroventricular dexamethasone induced a significant reduction in plasma levels of adrenocorticotrophic hormone, cortisol, arginine vasopressin and noradrenaline. In addition, simultaneous central administration of RU 38486 with intracerebroventricular dexamethasone blocked the reduction in blood pressure and heart rate completely. CONCLUSION: The present data strongly suggest that endogenous glucocorticoid in the central nervous system may not have a role in the regulation of systemic haemodynamics and hormones under resting conditions, but does play an important part during the glucocorticoid excess state, for example glucocorticoid hypertension caused by oral treatment with dexamethasone. The glucocorticoid in the central nervous system opposed the elevation of blood pressure in glucocorticoid-induced hypertension by attenuating the reduction in heart rate and cardiac output via direct stimulation of glucocorticoid receptors in the brain.

Blockade of the renin-angiotensin system in heart failure in conscious dogs.

OBJECTIVE: To study the different cardiac and renal hemodynamic effects of an angiotensin converting enzyme inhibitor and an angiotensin II receptor antagonist in experimental heart failure in conscious dogs. DESIGN AND METHODS: We compared the effects of the angiotensin converting enzyme inhibitor, captopril, with those of the angiotensin II (Ang II) subtype-1 receptor antagonist, losartan, on hemodynamics and hormonal changes in congestive heart failure by rapid ventricular pacing on conscious dogs. Furthermore, we characterized the Ang II receptors in canine heart, using the canine cardiac membrane fraction in heart failure. RESULTS: Acute intravenous administration of captopril improved the cardiac output by 19% (P < 0.01) but losartan did not, although blockade of the renin-angiotensin system by losartan (1.1 mumol/kg) or captopril (0.69 mumol/kg) induced similar changes in the plasma renin activity, norepinephrine and arginine vasopressin, and a similar decrease in mean arterial pressure (-10 mmHg). Renal blood flow was increased by either losartan or captopril. In the binding study, losartan produced a single displacement curve (IC50 = 0.25 mumol/l), while the Ang II subtype-2 (AT2) receptor antagonist PD123319 did not, indicating that the predominant Ang II receptor is type-1 (AT1) in canine heart. Neither the ratio of AT1 to AT2 receptors nor the receptor density changed with the development of heart failure. CONCLUSIONS: The lack of effect of losartan on cardiac output may be the result of its inability to block non-AT1 receptor-mediated Ang II activities adequately. Captopril may improve cardiac output by means of mechanisms not mediated by Ang II, such as locally increasing bradykinin.

Different effects of low and high doses of endothelin on haemodynamics and hormones in the normotensive conscious dog.

The effects of low-dose endothelin on systemic haemodynamics and vasoactive hormones were examined in conscious dogs. In addition, we examined the effects of endothelin on pressor responses to noradrenaline and angiotensin II and the baroreflex regulation of heart rate in conscious dogs. Continuous infusion of 40 fmol/kg per min endothelin for 40 min induced a mild but significant reduction in mean arterial pressure from 89.1 +/- 1.7 to 82.7 +/- 2.0 mmHg (P less than 0.05), associated with decreases in total peripheral resistance 20 min later. A 400 fmol/kg per min dose of endothelin, on the other hand, induced a gradual elevation of mean arterial pressure from 89.2 +/- 2.3 to 96.8 +/- 2.0 mmHg (P less than 0.05), associated with increases in total peripheral resistance over 30 min. The 40 fmol/kg per min dose of endothelin infusion induced a significant reduction in plasma arginine vasopressin (AVP; P less than 0.05) and elevations of plasma atrial natriuretic peptide (ANP; P less than 0.05), plasma prostaglandin E2 (PGE2; P less than 0.05) and plasma 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha; P less than 0.05). The 400 fmol/kg per min dose produced elevations of AVP, ANP, PGE2 and 6-keto-PGF1 alpha (P less than 0.05). Pressor responses to noradrenaline and angiotensin II were significantly attenuated during continuous infusion of 40 fmol/kg per min endothelin, whereas 400 fmol/kg per min endothelin did not induce any significant changes compared with the control. Furthermore, baroreflex sensitivity was attenuated with 40 fmol/kg per min endothelin but did not show any significant changes at 400 fmol/kg per min.(ABSTRACT TRUNCATED AT 250 WORDS)

Interactions between angiotensin II and norepinephrine on renin release by juxtaglomerular cells.

While the interactions between angiotensin II (Ang II) and norepinephrine (NE) on cardiovascular responses are well known, their effects on renin responses are not. We determined the renin secretion rate (RSR) and intracellular calcium level in juxtaglomerular cells harvested from Sprague-Dawley rats using a radioimmunoassay and a two-dimensional calcium analyzer. The effect of Ang II and NE was inhibitory on RSR and stimulatory on intracellular calcium. The NE-induced RSR response was amplified in the presence of Ang II (20 nmol/l). The NE-induced intracellular calcium response was also potentiated by the Ang II. There was a significant correlation (r = 0.994, p < 0.0001) between the changes in the RSR and those in intracellular calcium levels. Losartan (0.1 mumol/l). an Ang II type 1 receptor antagonist, blocked the Ang II threshold RSR responses and completely abolished the Ang II-related enhancements. The exclusion of calcium from the buffer reduced the maximal RSR response to NE but did not prevent the enhancement, suggesting the importance of the mobilization of intracellular calcium in the mechanism. The Ang II-induced RSR was amplified in the presence of NE (0.2 mumol/l). The Ang II-induced intracellular calcium response was also potentiated by the NE. A significant correlation (r = 0.996, p < 0.0001) between the changes in the RSR and the changes in intracellular calcium levels was also noted. Prazosin (1 mumol/l), an alpha 1-adrenoceptor antagonist, blocked the NE threshold RSR responses and abolished the agonist-related enhancements. The calcium-free buffer diminished this amplication with a slight decrease in the maximum RSR response to Ang II.(ABSTRACT TRUNCATED AT 250 WORDS)

Magnetic resonance imaging with gadolinium DTPA enhancement in patients with acute head injury.

Gadolinium-enhanced magnetic resonance (MR) imaging in patients with acute head injury was conducted to study if contrast extravasation was associated with development of hemorrhagic lesions. A series of 60 head-injured patients were admitted to our emergency unit. Computerized tomography (CT) scans and skull x-ray films were taken as rapidly as possible after hospitalization. Injury severity on admission was evaluated using the Glasgow Coma Scale (GCS) score, motor score, and pupillary examination, while overall outcome was assessed with the Glasgow Outcome Scale (GOS) 3 months after injury. Of all patients admitted, MR imaging with gadolinium enhancement was performed in 18 patients who were at high risk of developing hemorrhagic lesion within 6 h after injury. In these patients we investigated whether contrast extravasation was associated with development of hemorrhagic lesions. All 18 patients presented abnormal findings on their admission CT scans. Admission GCS score in those patients who underwent MR imaging with gadolinium enhancement was 13 or more in 12 patients, 9-12 in four patients, and 8 or less in two patients. Fourteen of 18 patients showed contrast extravasation, corresponding with an evolution of lesion size. Nine of 14 patients who demonstrated extravasation of the contrast medium required surgical treatment. The results of the current study suggest that extravasation of contrast medium indicates a continuance of posttraumatic bleeding. Thus, MR imaging with gadolinium enhancement in acutely head-injured patients may constitute a reasonable strategy for predicting the development of hemorrhagic lesions.

In vivo and in vitro characterisation of a nonpeptide vasopressin V(1A) and V(2) receptor antagonist (YM087) in the rat.

This paper reports the in vitro and in vivo characterisation of a nonpeptide, orally active, vasopressin V(1A) and V(2) receptor antagonist, YM087 (methyl-1,4,5,6-tetrahydroimidazo[4, 5-d][1]benzoazepine-6-carbonyl)-2-phenylbenzanilide monohydrochloride) in the rat. YM087 dose dependently displaced the vasopressin V(1A) receptor antagonist radioligand, 125I-labelled [d(CH(2))(5),sarcosine(7)]vasopressin at vasopressin V(1A) receptors in liver and kidney medulla membranes and caused a concentration dependent displacement of the vasopressin V(2) receptor antagonist radioligand [3H]desGly-NH(2)(9)[d(CH(2))(5), D-Ile(2), Ile(4)]vasopressin at vasopressin V(2) receptors in kidney medulla membranes. In vitro binding kinetic studies showed YM087 acted as a competitive antagonist at liver V(1A) and kidney V(1A) and V(2) vasopressin receptors. Oral administration of YM087 (0.1-3 mg/kg) dose dependently inhibited vasopressin binding to liver V(1A) and kidney V(1A) and V(2) vasopressin receptors over 24 h. Oral YM087 (1-3 mg/kg/day) for 7 days in normotensive rats caused a dose dependent aquaresis with no effect on systolic blood pressure. These results show that YM087 is an orally effective vasopressin V(1A) and V(2) receptor antagonist that may be useful in the treatment of conditions characterised by vasoconstriction and fluid retention such as congestive heart failure.

Elevated content and secretion of gut GLI in VMH-lesioned rats.

Gut glucagon-like immunoreactivity (GLI), a supposed intestinal growth factor in the plasma and gastrointestinal tract, and weight of the gastrointestinal tract, an intestinal growth indicator, were examined in ventromedial hypothalamic (VMH)-lesioned rats 1 week after VMH lesions. Postprandial plasma gut GLI in VMH-lesioned rats was significantly higher than that in control rats. The content of gut GLI in all gastrointestinal sections except the duodenum in VMH-lesioned rats was significantly greater than that in control rats. Gel chromatography in the lower portion of the small intestine in which GLI content was the highest of all sections revealed the same pattern in both VMH-lesioned and control rats with two peaks of similar molecular size. Weight of all gastrointestinal sections except the cecum in VMH-lesioned rats significantly increased. These results demonstrated that both gut GLI secretion and production were enhanced in VMH-lesioned rats. The elevated gut GLI release may accelerate growth of the gastrointestinal tract in these animals.

[Intestinal motility after massive small bowel resection].

To evaluate intestinal motility after 80% massive distal small bowel resection (MSBR), we continuously monitored interdigestive and postprandial bowel motility using bipolar electrodes and/or contractile strain gage force transducers in conscious beagle dogs before, and at 0-4 weeks and 8-13 months after the surgery. Fasting duodenal migrating myoelectric (or motor) complexes (MMCs) occurred at longer intervals in the short-term after 80% MSBR than in controls, and were simulated in long-term that in controls. MMCs arising from the duodenum were often migrated to the proximal jejunum, the jejunum above the anastomosis, and to the terminal ileum beyond the anastomosis. The velocity of duodenal MMC propagation was slowed in every intestinal segment in the short-term, and had not recovered even long after the operation. The duration of the postprandial period without duodenal MMCs was prolonged significantly in the short-term, and still remained longer in the long-term than in controls. These findings suggest that changes in gut motility after MSBR tend to compensate for the shorter intestine and maintain small bowel absorption early postoperatively, and adaptations of motility would occur over the long-term to increased intestinal absorption.

Hepatocellular carcinoma arising in an elderly male with primary biliary cirrhosis.

We report the case of an elderly male with asymptomatic primary biliary cirrhosis (PBC) who developed a hepatocellular carcinoma (HCC). The 89-year-old man, who was otherwise healthy, was admitted for investigation of mild hepatic dysfunction, which had been detected during a routine physical check-up. Serum chemistry, positive anti-mitochondrial antibody (M2) and liver biopsy results led to a diagnosis of PBC. Three years later, at age 92, computed tomography (CT) and ultrasound scans of his abdomen revealed a large hepatic tumour, which was confirmed on liver biopsy to be HCC. The tumour ruptured 3 months after diagnosis and the patient was successfully stabilized by coil embolization of his right hepatic artery. We believe that, to date, this is the oldest reported patient to have had interventional radiology for the management of HCC.

Thirst in elderly subjects.

The hormonal changes associated with ageing, the occurrence of other medical condition and the use of medications increases the likelihood of conditions such as hyper- and hypo-natremia. Awareness of the homeostatic changes with age and the relations with disease and drugs will lead better management of fluid disorders in the elderly patient and hopefully a reduction in morbidity and mortality.

Mediastinal yolk sac tumor in a young girl: case report and review of the literature.

The authors report a rare case of a female infant who underwent successful treatment of a mediastinal yolk sac tumor. Therapy included four cycles of preoperative PVB (cisplatinum, vinblastine, bleomycin), complete surgical resection of the tumor, and one postoperative cycle of PVB and four cycles of VAC (vincristine, actinomycine, cyclophosphamide) chemotherapy. The successful treatment of this tumor depends on preoperative chemotherapy to reduce the size, followed by complete surgical excision with subsequent postoperative chemotherapy. Recent improvements in the treatment of mediastinal yolk sac tumors are discussed.

Prediction of disseminated intravascular coagulation in patients with leukemia.

In 43 patients with leukemia, we determined the increase of tissue factor (TF) activity production by leukemic cells that was induced by incubation with endotoxin at the time of admission. Definite disseminated intravascular coagulation (DIC) developed in 8 patients on admission (Group III) and in 8 patients just after the initiation of treatment (Group II), but not in the remaining 27 patients (Group I). TF activity before incubation (TF1) was 0.70 U/10(8) cells or more in 6 patients of Group III, while it was less in all the patients of Group II and 25 of the 27 patients of Group I. On the other hand, TF activity after incubation with endotoxin (TF2) increased to more than 1.11 U/10(8) cells in all the patients of Groups II and III, while it remained less in all the patients of Group I. These results suggest that the leukemic cells in Group II might not have expressed sufficient TF activity to cause DIC until chemotherapy was begun, and that 1.11 U/10(8) cells or more of TF2 might strongly indicate the development of DIC during treatment for leukemia.

Odontogenic infection pathway to the submandibular space: imaging assessment.

The aims of this study were to determine the pathways of odontogenic infection spread into the submandibular space and their relationship to the clinical symptoms. Computerized tomography (CT) and magnetic resonance (MR) images of 33 patients with submandibular involvement were analyzed. The spread of infection was evaluated by lateral asymmetry of the shape and density of the fascial spaces and tissues, and by obliteration of the interfascial fat spaces. Imaging findings were classified into three types: in 19 patients (57.6%), infection spread through the mylohyoid muscle or sublingual space (type I). In five patients (15.2%), infection spread through the bony structures of the mandible with periosteal reaction or perforation of the cortical plate (type II) and was associated with relatively mild symptoms. In four patients (12.1%), infection spread from the masticatory space (type III). Seven of 11 patients with dysphagia or fever showed submandibular involvement spreading into the parapharyngeal space. CT and MR imaging clearly demonstrated different pathways of the spread of odontogenic infection into the submandibular space, which influenced the manifestation of clinical symptoms.

Joint Photographic Experts Group compression of intraoral radiographs for image transmission on the World Wide Web.

OBJECTIVE: The purpose of this study was to evaluate the subjective quality of Joint Photographic Experts Group (JPEG) compressed images of intraoral radiographs with file sizes of 30 kilobytes or less, which can be transmitted quickly on the World Wide Web. STUDY DESIGN: Conventional intraoral radiographs were digitized at sampling rates of 100, 200, 300, 400, and 600 dots per inch through use of a flatbed scanner and saved in JPEG format in 11 compression degrees. Fifty-five combinations of sampling rate and compression degree were evaluated by means of a visual analog scale. Sampling rate and compression degree combinations whose quality was inferior to that of an average image were excluded. The quality of the remaining combinations was subsequently evaluated through assessment of 8 anatomical features in each image. RESULTS: Forty of the 55 combinations provided a file size less than 30 kilobytes. Thirty combinations obtained VAS scores of 0 or higher on the standardized VAS. As a result, 16 combinations of sampling and compression conditions were selected for the second part of the study. Only one combination of sampling rate and compression degree was found to provide sufficient image quality for all 8 anatomical features. CONCLUSIONS: Under the file size limit of the study design, the full-sized compressed image of an intraoral radiograph did not always provide sufficient quality. This problem will be reduced by improvements in telecommunications infrastructure, which will permit faster transfer of files of larger size.

Observer agreement in the detection of proximal caries with direct digital intraoral radiography.

OBJECTIVE: The aim of this study was to compare several values for consistency obtained by charged-coupled-device-based direct digital intraoral radiography with those obtained by conventional film-based radiography to evaluate observer agreement in determining the depth of proximal caries. STUDY DESIGN: A total of 93 proximal surfaces on radiologic images that were obtained by both the conventional film-based bite-wing technique and by direct digital intraoral radiography were evaluated by six observers. One of these observers also evaluated the same images six months after the initial evaluation. The kappa value, consistency ratio, agreement ratio, and Kendall's correlation coefficient were calculated for interobserver and intraobserver agreement. RESULTS: The overall kappa values for interobserver agreement were 0.439 and 0.424 in the direct digital system and the film-based radiography, respectively. The depth-related change of the values showed similar patterns in the two modalities for both interobserver and intraobserver agreement. CONCLUSION: The digital intraoral system resulted in no deterioration in observer agreement, and it presents no problems for clinical use with respect to the reliability of diagnosis.

AutoCyte SCREEN interactive automated primary cytology screening system. A preliminary evaluation.

OBJECTIVE: To perform a preliminary evaluation of the relative sensitivity of a new interactive automated cytology screening system (AutoCyte SCREEN, AutoCyte, Inc., Elon College, North Carolina, U.S.A.) designed as a primary screening system for AutoCyte PREP monolayer slides (AutoCyte). STUDY DESIGN: Monolayer slides were prepared and evaluated in a masked review both manually and using the automated system. Human and machine performance was monitored and measured. RESULTS: Five hundred eighty-three monolayer preparations, including 56 clearly abnormal cases, were evaluated. The dual and combined computer and cytologist image evaluation resulted in a relatively low false positive rate, 20.8%, and 1.8% false negative rate. Use of the system was efficient, significantly reducing cytotechnologist screening time. CONCLUSION: The integrated AutoCyte cell preparation and automated screening approach seems to hold significant promise for primary cytology screening applications.

Sacrococcygeal teratoma: a series of 19 cases with long-term follow-up.

A series of 19 cases of sacrococcygeal teratoma (SCT) with follow-up of 5 to 25 years is presented. Twelve patients were neonates, age 0 to 26 days (5 immature teratomas and 7 mature teratomas, representing 3, 6, 2, and 1 Altman's type I, II, III, and IV tumors, respectively), four were infants, age 1 to 6 months (all mature teratomas, representing 1, 1, and 2 Altman's type I, II, and IV tumors), and 3 were children, age 1 to 4 years (all malignant teratomas, all Altman's IV tumors). Eight babies were delivered by elective caesarean section (CS). Though the mean gestational age at CS was 34.3 weeks in our series, we now believe that CS often must be performed earlier, depending on a tumor size or fetal condition. Eleven neonates and 4 infants were operated upon using a sacral approach in 10 and an abdominosacral approach in 5, and all survived. However, 4 patients had neurogenic bladder and were treated by urinary catheterization or vesicostomy for 2 to 5 years after surgery. Postoperative urogenital sequelae are seen in patients with a large tumor, urethral compression, urinary retention, or edema of the lower body. Malignant tumors usually had metastasized by the time of diagnosis, but the prognosis for outcome has been improved following surgery and combination chemotherapy.

[Coagulation disorders as early predictor of brain injury].

To identify early prognostic value of brain injury, a comparison was made between computerized tomography (CT) findings, coagulation abnormalities, and clinical features in 51 patients with closed head injury. The patients were divided into three groups according to their plasma level of fibrin-fibrinogen degradation product (FDP): normal group (FDP 10 micrograms/ml or less) in 20 patients; moderately abnormal group (FDP 10-40 micrograms/ml) in 15 patients; and highly abnormal group (FDP 40 micrograms/ ml or more) in 16 patients. Cases with a fatal clinical course were mostly associated with very high FDP level. Mortality rate in the highly abnormal group was 44% and 7% in the moderately abnormal group were dead cases, while no cases in the normal group turned out poor outcome. Injury severity, as assessed by Glasgow Coma Scale (GCS) score, correlated with the increase of plasma FDP level. Although severe head injury (GCS 8 or less) was found in 44% of the highly abnormal group and 13% of the moderately abnormal group, normal group only had one case (5%). Very high FDP concentrations were found to be associated with combined hemorrhagic lesions and mass effect on CT scan, but not with a specific localization of brain damage. In summary, the evaluation of coagulation and fibrinolytic function in patients following closed head injury might have both diagnostic and prognostic value.