RP 54745, a potential antirheumatic compound. II. In vivo properties in different animal models.

The results obtained with RP 54745, an amino-dithiole-one compound, on stimulated macrophages, revealing inhibition of the hexose monophosphate pathway (HMP), of the exocytosis of lysosomal enzymes and of the production of interleukin-1 (IL-1), by the compound in vitro as well as in vivo, suggested that RP 5475 might influence cells and cytokines implicated in the regulation of the immune system, the disfunctioning of which can lead to inflammatory disorders or autoimmune pathologies. RP 54745 was effective at moderate oral doses (around 5 mg kg-1) in different mouse models of induced arthritis and in the MRL/lpr mice, genetically predisposed to develop an autoimmune pathology including arthritic disorders. The clinical status of the MRL mice, and several of their disturbed biochemical and immunological parameters, improved after a 3-month treatment with RP 54745. This activity of RP 54745 makes it a very attractive antirheumatic compound and a potentially effective treatment in pathologies where IL-1 production is exacerbated.


Differences in proinflammatory activity of several immunomodulatory derivatives of muramyl dipeptide (MDP) with special reference to the mechanism of the MDP effects.

Immunomodulatory agents, muramyl dipeptide (MDP) and several of its analogues, i.e. adamantylamide dipeptide, murametide, murabutide and their glucosaminylated derivatives, were tested for edemagenic activity in rats. Given systemically in aqueous solutions, only MDP and glucosaminylated MDP, at the dose of 3 mg/kg (s.c. or p.o.), were found to produce edematous swelling of the paws. Local (intra-pad) application of MDP was more effective than the systemic one. Supernatants of macrophages, in vitro cultured in presence of MDP, caused the swelling as well. The edema was of a transient nature. After reaching the maximum severity (about 6 h after injection of MDP solution or 1 h after macrophage supernatants), it was subsiding and disappeared completely within approximately 6 days after cessation of the treatment. It was found that this type of rat paw edema is probably a prostaglandin-dependent consequence of macrophage activation. Hypotheses on the involvement of immunoregulatory cytokines, and possible chemical structure-inflammatory activity relationships have been suggested.


Zinc monoglycerolate--a slow-release source of therapeutic zinc: solubilization by endogenous ligands.

A combination of 65Zn-tracer determinations, oxidative analyses for glycerol, and a bioassay for uncomplexed Zn2+ have shown that: (i) zinc monoglycerolate (ZMG) dissolves in aqueous salt solutions/physiological media by dissociation into zinc ions and glycerol, but the rate and extent of ZMG dissolution depend upon pH, and/or concentration and complexing efficiency of zinc-ligands; (ii) under physiological conditions certain ligands present in skin and blood (e.g. citrate, lactate, albumin, histidine, glutathione and other thiols and, to a lesser extent, amino acids) accelerate ZMG dissolution; and (iii) there is a general correlation between the conditional stability constants (pH 7.3, 25 degrees C) of zinc-ligand complexes and the ability of given ligands to (a) solubilize ZMG in vitro and (b) mask the irritancy of Zn2+ in vivo. These observations indicate a mechanism for the transformation of ZMG applied transdermally or subcutaneously, to bioactive zinc (anti-arthritic nutritional supplement, etc.).


Role of the epithelium in the control of intestinal motility: implications for intestinal damage after anoxia and reoxygenation.

A vibration technique was used to dislocate the epithelium from the rat small intestine, in order to study the possible regulatory role of the epithelium on intestinal motility. Complete removal of the epithelium led to a slightly potentiated contraction of the longitudinal smooth muscle by the muscarinic agonist methacholine (pD2. 6.5 +/- 0.1 vs. 6.2 +/- 0.2). The maximal beta-adrenergic response expressed relative to the relaxation by 0.5 mM dibutyryl cyclic AMP increased from 55.9 +/- 9.0% to 72.6 +/- 9.1% by this treatment. Efforts were made to relate these observations to the endothelium-dependent relaxation in blood vessels, but no indication was found for a similar mechanism in the small intestine. Not only mechanical dislocation can be employed to affect the mucosal layer, but also intestinal ischemia has been reported to lead to mucosal damage. In this study we mimicked ischemia by applying in vitro anoxia and subsequent reoxygenation to isolated intestinal segments. When intestinal segments are isolated and kept in physiological buffer, xanthine dehydrogenase is converted slowly to xanthine oxidase, irrespective of whether the buffer is oxygenated or not. No evidence was found for oxygen radical damage after anoxia and reoxygenation. However, the intestinal mucosa was damaged both after normoxia, and after anoxia and reoxygenation. Anoxia and subsequent reoxygenation did not affect muscarinic contraction, but slightly increased the beta-adrenergic relaxation, which partly correlates with the effects of mechanical dislocation of the epithelium. The increased sensitivity of the smooth muscle after epithelial damage might be involved in motility changes during intestinal inflammatory diseases.


Effect of BW443C81, a novel opioid, on non-cholinergic bronchoconstrictor responses and neurogenic plasma extravasation in the guinea pig.

The novel, peripherally acting opioid peptide, BW443C81, which attenuates airway sensory nerve impulses, was examined on non-cholinergic (NC) constrictor responses in vitro and in vivo and neurogenic plasma extravasation in vivo in guinea-pig airways. Non-cholinergic contractions of guinea pig isolated bronchi, evoked by electrical field stimulation, were concentration-dependently inhibited by BW443C81 and morphine (10 nmol/1-100 mumol/l). In anaesthetised, artificially ventilated guinea pigs, frequency-related NC bronchoconstrictor responses evoked by antidromic electrical stimulation of the vagus nerves were reduced by BW443C81 (100 micrograms/kg/min i.v. infusion) and morphine (1 mg/kg i.v.). Neurogenic plasma extravasation produced by bilateral electrical vagal nerve stimulation in spontaneously breathing, anaesthetised guinea pigs was also inhibited by BW443C81 (1 mg/kg i.v.). The inhibitory effects of BW443C81 were reversed/prevented by naloxone. BW443C81 inhibits NC bronchoconstrictor responses and neurogenic plasma extravasation in guinea pig airways, consistent with its previously described mu-opioid receptor-mediated inhibitory action on airway sensory nerve function.


Vasoconstriction and bronchoconstriction induced by 2,5-di-(tert-butyl)1,4-benzohydroquinone, an endoplasmic reticular Ca2+-ATPase inhibitor, in isolated and perfused rat lung.

The microsomal Ca(2+)-ATPase inhibitor 2,5-di-(tert-butyl)-1,4-benzohydroquinone (tBuBHQ) induced bronchoconstriction and vasoconstriction in the isolated perfused and ventilated rat lung. These effects were accompanied by increased levels of thromboxane and prostacyclin in the effluent perfusate. The effect of tBuBHQ was inhibited by L-655,240, a thromboxane receptor antagonist, indicating thromboxane-A2-mediated bronchoconstriction and vasoconstriction. Accordingly, the cyclooxygenase inhibitor indomethacin largely blocked the effects of tBuBHQ. The involvement of a phospholipase in the generation of thromboxane A2(TXA2) was supported by dibucaine protection on tBuBHQ effects. The results from this study indicate that tBuBHQ, probably by inhibiting the microsomal Ca(2+)-ATPase, can trigger the arachidonic acid cascade leading to the formation of TXA2, which in turn causes bronchoconstriction and vasoconstriction in rat lung.


Separate induction of human blood platelet aggregation or cytotoxicity by different concentrations of PAF-acether and thrombin.

Using decreasing concentrations of PAF-acether or thrombin, it was possible to observe on human platelets, first, aggregation, classically associated to activation, then , below a threshold, cytotoxicity towards Schistosoma mansoni larvae, proposed here as stimulation. These two activities appeared as distinct and antithetic. However, their induction might be the consequence of triggering of the same receptors with different intensity, since PAF-induced, but not thrombin-induced, cytotoxicity could be inhibited with specific PAF-antagonists BN 52021 and BN 52024 also known to inhibit PAF-induced aggregation. These results give credit to the hypothesis that haemostatic and cytotoxic properties of platelets are two distinct functions of these blood elements.


Inhaled budesonide regimen enhances serotonin- and arachidonic acid-induced platelet aggregation.

The influence of inhaled budesonide regimen (400 micrograms x 2 for 7 days), on agonist-induced platelet aggregation and secretion, was investigated in 18 volunteers. Platelet activation induced by serotonin and arachidonic acid was significantly enhanced after budesonide, as demonstrated by an increase in aggregation velocity (Vmax) and amplitude (Amax), and in arachidonic acid-induced ATP-secretion. We found no change in platelet aggregation induced by ADP, epinephrine, and A23187. With the exception of epinephrine-induced platelet aggregation, which was inhibited by 10(-5)-10(-4) M budesonide, in vitro studies revealed no influence of 10 min budesonide preincubation (10(-9)-10(-4) M) on agonist-induced platelet activation, suggesting that the ex vivo enhancement of platelet function was mediated by secondary corticosteroid mechanisms. A tentative explanation of the increased arachidonic acid-induced platelet activation, may be a budesonide-induced stimulation of cyclooxygenase. The enhanced serotonin-induced platelet aggregation may be a reflection of exogenous corticosteroid stimulation of the 5-HT2-receptor.


Rapid and sensitive detection of hydroxyl radicals formed by activated neutrophils in the presence of chelated iron: hydroxylation of deoxyguanosine to 8-hydroxydeoxyguanosine.

Hydroxyl radicals (OH) can react with deoxyguanosine (dG) leading to the formation of 8-hydroxydeoxyguanosine (8OHdG). In this study, this has been used to detect the hydroxyl radicals formed when human polymorphonuclear leukocytes (PMNL) are stimulated with phorbol myristate acetate (PMA) in the presence of chelated iron. Reaction mixtures containing PMNL, PMA, dG and Fe-EDTA were incubated at 37 degrees C, and the formation of 8OHdG was analysed with high-performance liquid chromatography and electrochemical detection. 8OHdG formation was detected at PMA concentrations of 2 nM or higher, and half-maximal 8OHdG formation was found at around 6 nM PMA. Stimulation of 500,000 cells with 10 nM PMA for 20 min resulted in a 500 to 1000-fold increase in 8OHdG formation as compared to unstimulated cells. The 8OHdG formation decreased after addition of hydroxyl radical scavengers (sodium benzoate, dimethylsulfoxide, and mannitol) and increased after addition of platelet-activating factor (PAF), an agent known to stimulate the generation of reactive oxygen metabolites in neutrophils. These results demonstrate that hydroxylation of dG to 8OHdG can be used to determine neutrophil-generated hydroxyl radicals in different experimental systems. Since the analysis of 8OHdG is rapid, sensitive and easy, this may have wide applications in inflammation and cancer research.


The pneumotoxicant paraquat potentiates IL-1 and TNF production by human mononuclear cells.

Interleukin 1 (IL-1) and tumor necrosis factor (TNF) have been implicated in the pathogenesis of bleomycin- and silica-induced lung damage. We have studied the effect of paraquat (PQ), a well-known pneumotoxicant, on IL-1 and TNF production by human peripheral blood mononuclear cells from different healthy donors stimulated with endotoxin. PQ (100 microM) potentiated IL-1 production (2-40 fold) and TNF production (2-18 fold). It is, therefore, possible that IL-1 and TNF are also involved in the pneumotoxic action of PQ.


Biphasic regulation by dexamethasone of IL-1- and LPS-stimulated endothelial prostacyclin production.

Body reaction to injury comprises two major pathways: the immune response, predominantly mediated by IL-1 and other cytokines, and neuroendocrine mechanisms, resulting in an increased glucocorticoid production. Each has distinct effects on prostaglandin (PG) production, which may in turn mediate both systemic and local inflammatory responses. The interactions, if any, between the two systems on PG synthesis have not been studied. Bovine aortic endothelial cell cultures were used and prostacyclin (PGI2) production was monitored. Cells were treated with dexamethasone (Dex) 10(-6) M and IL-1 10-30 U/ml in one experiment, and lipopolysaccharide (LPS, 0.1-1.0 micrograms/ml) in another experiment, separately or in combination, for either 2 or 24 + 2 h. While Dex was without effect, IL-1 and LPS stimulated PGI2 in a concentration- and time-dependent manner. Short exposure to Dex (2 h) enhanced the stimulation by IL-1 and LPS. On the contrary, more prolonged exposure (24 + 2 h) reversed the effects of IL-1 and LPS, resulting in PGI2 levels below the baseline. A biphasic regulation by Dex was also observed with increasing concentrations of LPS. Dex was actually ineffective by itself, but it enhanced PGI2 production in combination with lower concentrations of LPS, while abolishing the influence of higher concentrations of this agonist. The data suggest that Dex may initially stimulate phospholipase A2 (PLA2) activity, while inhibiting it later. This biphasic behavior may be attributed to different concentrations of a PLA2-modulating protein, possibly lipocortin, that accumulate during exposure to Dex.


Effect of prostaglandin E2 and 3-morpholinosydnonimine (SIN-1) on arachidonic acid metabolism in fMLP-stimulated rat neutrophils and on thrombin-induced human platelet aggregation.

The effects of prostaglandin (PG) E2 and the nitric oxide (NO) donor SIN-1 on leukotriene (LT) release from formyl-methionyl-leucyl-phenylalanine (fMLP) (100 nM)-stimulated rat peritoneal neutrophils (RPN) and on thrombin-induced aggregation of washed human platelets were investigated. Both PGE2 (1-100 nM) and SIN-1 (30-300 microM) inhibited release of LTB4 and cysteinyl-LT from RPN in a concentration-dependent manner. The combined effects of PGE2 and SIN-1 were not greater than expected by summation. On the other hand, the inhibitory effect of SIN-1 (0.5 or 1.0 microM) on platelet aggregation was potentiated by PGE2 (0.3-5 microM) in a concentration-dependent manner, while PGE2 alone in the concentrations used had only marginal effects. The results suggest differential regulation of platelet and leukocyte functions by the mediators PGE2 and NO, which could be relevant for various physiological and pathophysiological conditions.


Effects of prolactin on rat paw oedema induced by different irritants.

Evidence suggests that prolactin (PRL) may have a role in immune function, but no data exist on the possible interference between PRL and inflammatory processes, in spite of the known correlation between inflammatory and immune reactions. In the present study the activity of prolactin on rat paw oedema was investigated. Repeated administrations of ovine PRL or a hyperprolactinaemia induced by pituitary gland graft provoked an evident increase of the inflammatory response induced by carrageenan. This effect was also present when adrenalectomised animals were used. Indomethacin completely suppressed the pro-inflammatory effect of ovine PRL; bromocriptine reduced the paw oedema, but when both bromocriptine and PRL were administered the two opposite effects seem to annual each other. Also phospholipase A2-induced paw oedema was potentiated by PRL pretreatment and inhibited by bromocriptine, whereas in dextran or serotonin-induced paw oedema both PRL and bromocriptine were ineffective. A possible involvement of prostaglandins and/or of phospholipase A2 in the pro-oedemigenic activity of PRL is suggested.


Interaction studies of tilomisole, aspirin, and naproxen in acute and chronic inflammation with assessment of gastrointestinal irritancy in the rat.

The effect of combination NSAID therapy of tilomisole with aspirin or naproxen was studied in rats with carrageenan-induced paw edema and established adjuvant arthritis. Inflamed paws were measured using mercury plethysmography and the arthritic paws were X-rayed to determine any bony/soft tissue changes. The gastrointestinal tract was also examined for bleeding and ulceration. Tilomisole had a less potent acute anti-inflammatory effect than aspirin or naproxen, but produced no significant gastrointestinal damage. A significant reduction in anti-inflammatory activity was observed with the tilomisole/aspirin combination in acute inflammation. Only additive interactions were observed with the naproxen inhibition. In the established arthritis assay, a significant synergistic anti-inflammatory response, i.e. both inhibition of paw edema and bone erosion, was also observed with the 80 and 93% tilomisole/naproxen combinations. The gastric ulcerogenic effect of the combination paralleled its increased activity. The synergism between tilomisole and naproxen in this chronic arthritic model may be due to enhanced cyclooxygenase inhibitory activity. These drug interaction studies suggest possible interactions in human clinical trials of rheumatoid arthritis.


[Deterioration of amplitude of the accommodation with age and its possible restoration in the intraocular lens implanted eye].

This study aimed to determine whether pseudophakia which have deteriorated amplitude of accommodation with age, i.e., presbyopia and which received implantation of refractively changeable intraocular lenses after cataract extraction are able to regain accommodative function. According surveys on aging in the literature, functional deterioration of the ciliary muscle and the zonular fiber is not so striking compared to the changes of crystalline lens material and capsule. Consequently the artificially pseudophakic eye can be expected to regain accommodative function when the crystalline lens material could be replaced by an appropriately visco-elastic material before 80 years of age when the crystalline lens capsule still retain its elasticity.


[Effects of pre-instilled mydriatics on the intraocular concentration and anti-inflammatory action of topical 0.1% pranoprofen (2)--Study on multiple dosing].

We studied the effects of multiple dosing and pre-instilled mydriatics (0.5% tropicamide and 0.5% phenylephrine) on the intraocular concentration and anti-inflammatory action of topical 0.1% pranoprofen (PPF) in rabbit eyes. PPF was applied in a single or multiple doses: 1 to 4 times consecutively at 5-minute intervals with or without pre-instilled mydriatics. PPF concentrations in the aqueous humor increased dose-dependently. The PPF concentrations also increased dose-dependently, and reached the maximal concentration by instillation 3 times in the presence of pre-instilled mydriatics, and the concentrations were 3.4 to 5.8 times higher than those without mydriatics. The PPF concentrations in the cornea, secondary aqueous, and iris-ciliary body increased in a dose-dependent manner, and the concentrations were higher in the presence of mydriatics. PPF reduced the protein rise in the secondary aqueous and miotic responses which were seen after paracentesis. The percent inhibitions ranged from 75 to 83, but the inhibitory actions were not enhanced by increases of intraocular PPF concentrations. These data indicate that the potent anti-inflammatory actions of PPF were obtainable by a single instillation, but it might be useful to instill the drug 3 times consecutively to ensure higher intraocular drug concentrations in combination with pre-instilled mydriatics.


[Implantation of IOLs with different diameters].

The intraocular lenses (IOLs) commonly used today are 13.5 to 14 mm in diameter, and this diameter is considered by some to be unnecessarily large. The size of the crystalline lens and the diagonal width between the ciliary sulcus were measured in rabbit eyes and human eyes. Then, IOLs with a smaller diameter (12.5 mm) were evaluated after implantation into rabbit eyes. The mean diameter of the human crystalline lens was 9.6 mm and its thickness was 4.1 mm. The mean width of the ciliary sulcus was 11.1 mm. The crystalline lenses of rabbits were larger than those of humans. Decentration and posterior capsular opacification score were 0.33 mm and 0.63 in 12.5 mm IOL, and 0.47 mm and 0.61 in 14.0 mm IOL. Indicating that the result of implanting the 12.5 mm IOL was not inferior to that of implanting the conventional 14 mm IOL. The average width of the ciliary sulcus is 11.1 mm, indicating that a 12.5 mm IOL is of a sufficient size to be firmly fixed in this sulcus. In addition, a 12.5 mm IOL is considered to be safer, because larger lenses may lead to erosion or vessel compression that could induce ischemia or neovascularization.


[An experimental study of the surgical trauma on the rabbit's lens suspensory apparatus after cataract surgery].

Extracapsular cataract extraction (ECCE) and posterior chamber intraocular lens (PC-IOL) implantation requires that the posterior capsule and the zonules remain sufficiently intact. To assess the surgical trauma on the lens suspensory apparatus of the enucleated rabbit eye, we developed a new fine pressure gauge that could quantitate its strength. The cornea and the iris of enucleated eyes were removed to allow clear visualization of the anterior surface of the lens to the equator. Afterwards several types of anterior capsulotomy were performed for ECCE and PC-IOL implantation. And then the lens of the pseudophakic eye was vertically pressed with the plastic rod of the fine pressure transducer, and the strength of the lens suspensory apparatus was simultaneously measured. The strength of the lens suspensory apparatus of the pseudophakic eye decreased approximately 35% compared with that of the phakic eye. Moreover the integrity of the lens capsule of animals with circular capsulorhexis with tears or linear capsulotomy decreased approximately 43% compared with that of continuous circular capsulorhexis (CCC) and also zonular rupture and vitreous loss occurred as a result of the expansion of radial tears in the anterior capsule. The present study indicates that the strength of the lens suspensory apparatus decreases with cataract surgery, suggesting that much more attention to cataract surgery is needed if the anterior capsule had radial tears. It is also suggested that CCC is the best type of anterior capsulectomy procedure.


[Pathology of IOLs placed in the capsular bag of white rabbit eyes].

The authors performed a histopathological study to observe the surface of IOLs placed inside the capsular bag of white rabbit eyes. While a cellular reaction to the haptics was indicated by lens epithelial cells and collagen fibers surrounding the haptics, a wound healing reaction at the anterior capsule-optic junctions was suggested by an extensive amount of spindle cells and collagen fibers. However, collagen fibers and degenerated cells on the optics could be seen only under electron microscopy. Regenerated lens fibers, lens epithelial cells, and proliferation of spindle cells were noted between the posterior side of the optics and the posterior capsules.


[Retinal damage induced by visible blue and near-infrared light of an operating microscope].

The authors evaluated possible hazards to the retina caused by the longer wavelength component in the illumination system of the surgical microscope. Thirty six pigmented and eleven albino rabbit eyes were exposed to blue or near-infrared light for 60 minutes. Ophthalmoscopically visible light damage to the retina developed in 4 of 5 pigmented rabbit eyes after illumination at a power setting of 8 mW/cm2 for blue and 50 mW/cm2 for near-infrared light. These power settings were equivalent to those used in clinical tests. The light damage developed immediately after illumination with near-infrared light and a few days after illumination with blue light. No light damage developed in albino rabbits with near-infrared light at current power setting. The findings suggest the possibility that clinical retinal damage may develop in human eyes when exposed to near-infrared light from surgical microscopes.


[The existence of vasomotor nerve in the retina of the rabbit and monkey].

In the first stage of this study, peri- or intravascular unmyelinated nerve axon which was clearly different from that of the optic nerve was confirmed in the rabbit retina transmission electron microscopically. In the second stage, the correlation of these unmyelinated nerves and autonomic nerve was studied in rabbits and monkeys. For the purpose, wheat germ agglutinin horseradish peroxidase (WGA-HRP) was injected into the superior cervical ganglion. Electron microscopic observation of the retina 48 hrs after the injection of WGA-HRP showed deposit of its reaction product in the axon of the unmyelinated nerve located around the vascular wall and in the adventitia and smooth muscle cell in both rabbits and monkeys. This result clearly reveals the existence of an autonomic vasomotor in the retinal vessels at least in rabbits and monkeys.


[Experimental study on earlier thrombogenic process in thrombin induced retinal venous obstruction in rabbit eye].

The purpose of this study was to morphologically investigate the thrombogenic process in the early stage of retinal venous obstruction development. Venous obstruction was induced by transadventitial instillation of thrombin (5 units) given to the rabbit retinal vessels via a sclerovitreous route. The changes were studied by ophthalmoscopy, fluorescence microscopy combined with an intravenously injected gelatin fluorescein preparation technique as well as light and electron microscopy. No ophthalmoscopic change was seen within 1 hr after thrombin instillation. Three hour after thrombin instillation, focal narrowing of retinal arterioles was found with intraluminal platelet aggregation and rouleaux formation of erythrocytes. On electron microscopy, a large number of monocytes was observed in the lumina and subendothelial space of a pericytic venule having a partial endothelial defect as well as monocyte adhesion to its luminal surface. At more than 6 hrs, subendothelial thrombi were observed in the venules without any endothelial lesion while no change was observed in the arterioles, capillaries and pericytic venules. These findings suggested the possibility of participation of the arteriolar lesion in the occurrence of retinal venous obstruction and the role of endothelial lesions caused by blood stasis in subendothelial thrombogenesis.


[Gene rearrangement analysis of conjunctival malignant lymphomas].

Specific DNA probes for genes encoding immunoglobulins (Ig) and the T cell receptor (TCR) are useful diagnostic tools in lymphoproliferative disorders. Gene rearrangement analysis was carried out in 2 cases of conjunctival lymphoid lesions. A 36-year-old man (case 1) had a 1-year history of left conjunctival tumor. A biopsy was performed and histopathological findings showed diffuse proliferation of small lymphocytes, but monoclonality was not revealed by immunophenotypic analysis. A right conjunctival lesion developed and five months later a biopsy of the left conjunctiva was performed again. A frozen sample was analyzed and immunoglobulin heavy chain gene rearrangement was found. A 53-year-old woman (case 2) had a 6-month history of bilateral conjunctival tumor. The first biopsy did not reveal monoclonality immunophenotypically. A second biopsy with a frozen specimen was analyzed and immunoglobulin heavy chain gene rearrangement was found. We diagnosed these two cases as B-cell lymphoma. We discuss the clinical value of gene rearrangement analysis as a diagnostic method for lymphoproliferative disorders.


[Seasonal variation of intraocular pressure after trabeculotomy].

The author reviewed the seasonal variation of intraocular pressure (IOP) in primary open angle glaucoma or late type developmental glaucoma to investigate possible relationships among seasonal variation of IOP, progression of visual field defects and the follow-up period between 53 eyes of 39 subjects with successful trabeculotomy (trabeculotomy group) and 45 eyes of 31 subjects with only medication (no operation group). IOPs in both groups were inclined to be low in summer and high in winter. Maximum seasonal variation of IOP and standard deviation of IOP during all follow-up periods which showed the degree of seasonal variation of IOP had no significant difference between the trabeculotomy group and the no operation group. These results showed that seasonal variation of IOP was not reduced even by successful trabeculotomy. The maximum seasonal variation of IOP and standard deviation of IOP had a tendency to be bigger in cases with progression of visual field defects than in cases with no progression of visual field defects, in both groups. Therefore, seasonal variation of IOP may be an important factor influencing the progression of visual field defects.


[Statistical analysis of relationship between microalbuminuria and diabetic retinopathy].

The relationship between microalbuminuria indicated by the logarithm of the albumin index and the stage of diabetic retinopathy was investigated using 175 diabetic subjects. The relationship and its dependence on the duration and the age of onset of diabetes were analyzed statistically with logistic regression. In younger-onset subjects, microalbuminuria was strongly related to the stage of retinopathy, but in older-onset subjects, the relationship showed to lack. For each subject, the frequency of retinopathy was predicted by the estimated probability calculated with the regression model. When the critical probability was 50%, the sensitivity and specificity were 53.1% and 76.2%, respectively. These results indicated that the regression model using the albumin index might be a useful method to predict the frequency of diabetic retinopathy even without ophthalmoscopic examination.


[Reticular degeneration of retinal pigment epithelium].

Reticular degeneration of the retinal pigment epithelium (RDRPE) was found in 33 out of 3114 files (1.06%) of fluorescein angiography. The age distribution of the cases with RDRPE showed a peak in the 8th decade, and the average age was 73 years. No statistically significant sexual tendency was observed. Eighty five percent of cases had bilateral RDRPE. The linear, incomplete polygon type was found on the nasal quadrants in patients aged 50-70 years old. The complete polygon type was found in both nasal and temporal quadrants in patients over 70 years old. RDRPE and pigment epithelium degeneration at the posterior pole were found to be concomitant manifestations. It was concluded that RDRPE initially appears on nasal quadrants as a lineal, incomplete polygon pattern and in advanced cases complete polygon pattern appears on all quadrants of the peripheral retina.


[A case of chronic progressive external ophthalmoplegia with Oguchi's disease].

A 52-year-old case of chronic external ophthalmoplegia accompanied by Oguchi's disease was reported. The patient noticed night blindness and deafness since childhood. Later he developed ocular movement limitation to all directions by the age of 40. He had 20/20 corrected visual acuity and normal anterior segment, as well as normal color vision. Goldmann's perimetry showed generalized constriction of the peripheral field. Golden tapetal reflex without dark adaptation disappeared after 4 hours of dark adaptation, i.e. Mizuo-Nakamura's phenomenon was recognized. Recovery of diminished a and b wave electroretinogram to the subnormal range was also observed after 4 hours of dark adaptation. Rod-cone interaction test revealed a monophasic adaptation, and no suppression to the cones from the rods was observed. This finding was also compatible with Oguchi's disease. ECG revealed incomplete atrio-ventricular as well as right bundle branch blocks. Neurological examination findings were entirely normal other than slight enhancement of deep tendon reflexes in the lower extremities and mixed typed difficulty of hearing. Muscle biopsy of the right medial rectus muscle revealed ragged-red fiber, suggesting mitochondrial abnormalities. Never the less the quadriceps femoris muscle biopsy specimen showed normal histological findings. This is the first case report of progressive external ophthalmoplegia associated with Oguchi's disease. Mitochondrial abnormality was confirmed only in the external ocular muscle. This case may be a variant of Kearns-Sayre syndrome.


[A caruncular oxyphilic adenoma with an appearance of apocrine type secretion].

The histopathological and cytological findings of a caruncular oxyphilic adenoma (oncocytoma) in a 85 year-old male is described. The columnar or polygonal tumor cells contained numerous eosinophilic fine granules (mitochondria). They showed papillary proliferation and cyst formation. Electron microscopically, some tumor cells contained amorphous cytoplasm and small numbers of mitochondria in their apical snout, and secreted the contents in the extracellular spaces. It seemed that the tumor cells originated from the ductal epithelia in the caruncle and microscopically some cells simulated apocrine type secretion.


Urethroplasty of recurrent urethrocele: study of 41 cases.

Recurrent urethrocele is not often successfully treated surgically because, as is well known, pre-operative sterilization of the urethrocele is difficult, especially when it is very large. Furthermore the incomplete excision of the corpus callosum, because of the loss of urethral tissue this involves, often leads to post-operative fistulas and stenoses. This is why, very often, there are relapses no matter what technique is adopted. In 1978 both Juraschek and ourselves published a technique, derived from Monseur, in which the urethrocele and the corpus callosum were completely excised. The resulting loss of urethral tissue was remedied with the albuginea from the ventral surfaces of the corpora cavernosa after a 180 degrees rotation of the urethra. The results of this treatment in 41 cases of recurrent urethrocele are given in this paper. The follow-up period for the patients was from 15 to 2 years. Results have been excellent with very few complications (2 post-operative fistulas and 2 urethra stenoses). There have been no relapses.


Xanthogranulomatous pyelonephritis in pelvic ectopic kidney.

Xanthogranulomatous pyelonephritis occurred in a pelvic ectopic kidney in a 70-year-old man. Pre-operative diagnosis was possible due to the typical appearance at CT scan of central lithiasis and multiple rounded areas of low density with enhancing rims (bear paw sign).


Non functioning adrenocortical carcinoma. A rare case.

Adrenocortical carcinoma is a rare tumor and experience in its diagnosis and treatment is limited. We present a case of non functioning adrenocortical carcinoma in which the pre-operative diagnosis of a kidney tumor had been made and a radical nephrectomy was performed.


A case of epidermoid cyst of the testis role of conservative surgery.

We report one case of an epidermoid cyst of the testis in a 15 year-old boy. Pre-operative testicular ultrasound may help to establish the diagnosis without resorting to orchiectomy. In such a selected case local excision alone should be considered adequate without violating accepted surgical principles.


Corporeal reconstruction and prosthetic implantation for impotence associated with non-dilatable corporeal cavernosal fibrosis.

Thirty patients with severe cavernosal body fibrosis, secondary to various etiologies, underwent penile prosthetic implantation with cavernosal reconstruction using Gortex grafting material. The overall success rate was 70% (21 of 30 patients). Infection was the most significant postoperative complication and required device removal in 9 patients. This operative procedure was the only option these patients had in hope of restoration of erectile function for satisfactory sexual intercourse. We continue to recommend this procedure to the highly motivated, carefully selected patient.


Emergency percutaneous nephrostomy in the septic kidney.

From 250 upper tract obstructive uropathy cases we have studied 64 patients hospitalized with toxico-septic shock. The constant symptom was arterial hypotension. Other 3 patients with long-standing urinary infection due to lithiasis developed this dreaded complication after PNL (staghorn stones-2, pyelic stone-1). In complicated obstructive uropathy cases associated with toxico-septic shock, percutaneous nephrostomy for high urinary derivation in emergency is usually made under local anaesthesia. Its aim is rapid and efficient clearance of kidney obstruction, with minimal damage for the patient; then it is followed by strong antibiotherapy associated with other reanimation and intensive care measures. There were 11 deaths. The stone generating obstructive uropathy was removed subsequently, after the improvement of biological constants and general state of the patient, under the protection of percutaneous nephrostomy.


Anuria due to lithiasis associated with septic shock.

During 18 months 38 patients with anuria due to lithiasis were admitted in our department, 8 of them developed septic shock. Twenty eight patients were cured using different procedures and were released from the hospital with normal urinary output. Ten patients died, 6 of them from septic shock, which has a high mortality rate. Emergency restoration of urinary flow, correction of fluid and electrolyte imbalance, massive antibiotherapy may improve results.


Urosepsis. Clinical aspects--therapy--results.

Nine cases of urosepsis registered between 1986 and 1990 are analyzed. Authors intended to find out practical conclusions which can improve the prognosis of urosepsis. Risk factors are considered advanced age, preoperative disorders (diabetes, malnutrition), preexistent end organ failure (kidney, liver, lung) and urinary infection. Early diagnosis, emergency restoration of urinary flow, suppression of primary focus of infection, intravenous antibiotherapy and energetic intensive care measures are necessary for the outcome of patients.


Clinical comments on management of urosepsis in a general urological department.

Over a period of 6 years 192 cases of urosepsis have been recorded and managed in our urological department. In almost all cases (97%) the primary focus of infection was the urinary tract and the responsible microorganisms were Gram-negative rods, in order Enterobacter, B. Proteus, E. Coli, Klebsiella and others. Clinical features were dominated by symptoms related to failure or insufficiency of end organs (fever, hypotension, oliguria, mental disorders, respiratory distress etc.). Bacteremia was diagnosed with an incidence of 66%, septic shock 12% and MSOF 20%. Negative bacteriological tests do not rule out the diagnosis of systemic infection. Risk factors are considered advanced age, uremia, diabetes, malnutrition and extensive surgery.


Urodynamic findings in patients below 12 years old with different clinical types of enuresis.

We examined 50 children younger than 12 years old with different clinical types of enuresis. Urodynamic disorders were found in many patients. Our results indicate that the more clinical symptoms are present, the more frequently urodynamic dysfunctions are found.


Sensory disorders of the lower urinary tract: urodynamic evaluation.

Sensory disorders of the lower urinary tract (urethral syndrome, prostatodynia, painful pelvic-perineal syndromes, trigonitis) are clinically frequent, however this diagnosis is possible only by excluding other pathologies after clinical and instrumental evaluation. The Authors report their experience in urodynamic evaluation of sensory disorders of the lower urinary tract and they discuss about the absence of a typical urodynamic pattern of sensorial pathology.


A pseudotumoral edema of the urinary bladder secondary to an intramural impacted ureteral lithiasis.

A case of pseudotumor of the urinary bladder secondary to intramural lithiasis is reported. Computer tomography, cystoscopy of the mass and cytology suggested a malignant tumor. A transurethral biopsy from the tumor was therefore performed, but it showed tissue covered with normal transitional cell epithelium but no signs of malignancy. Pseudotumoral edema of the bladder is easily mistaken for a malignant neoplasm (1, 2, 3).


The vacuum erection device. A noninvasive treatment for impotence.

In 30 men we have tested the vacuum device after determining the cause of their impotence. 90% achieved penile rigidity sufficient for vaginal penetration. 10% didn't want to use it. Of the 30 men 20 (66%) reported that they used the device regularly after at least 6 months. In 4 patients the development of ecchymoses and petechiae was the reason to stop using the device. The vacuum device appears to be a safe, noninvasive and effective treatment for all causes of impotence.


Magnetic resonance imaging of a penile fracture.

A case of a penile fracture is reported. Magnetic resonance (MR) imaging clearly demonstrated the tear of the tunica albuginea. MR imaging helps us to decide the site of the skin incision.


[Obstructive urinary tract diseases and prenatal diagnosis. Timing of surgical correction].

The Authors are reviewing their experience of Obstructive Uropathies diagnosed and treated surgically in neonates, the last 8 years in their Institution. 67 cases were reviewed, in which 37 presented with ureteropelvic junction obstruction (UPJ). 13 with posterior urethral valves, 11 with primary megaureter and 6 with ureterocele. Prenatal ultrasonography allowed the diagnosis to be made in two third of the patients. UPJ is the most common obstructive uropathy observed. Posterior urethral valves the most severe because of high pulmonary and renal (dysplasia) complication rate. Surgery, when indicated, has no more complications to be expected than in general population, if oriented prophylactic measures are taken in the early peri- and postoperative period.


[Aneurysm of the renal artery and its infarct complications (clinical case and literature review)].

The authors are reporting the case of a 74 year old man, presenting a renal artery aneurysm. Regarding clinical aspects, medical treatment was elected. The most frequent cause of renal infarct is embolisation arising from the heart, followed by large vessels emboli that are more exceptional. Embolisation arising from the renal artery aneurysms is not very common. Unless contra-indications, surgical cure of the aneurysm is necessary, except those that are non complicated, with a diameter of less than 1.5 cm.


A mysterious cyst on the corpora in a patient with ulcerative colitis.

A case of a man with a cystic tumor destroying the corpus cavernosum at the penile basis is described. A surgical excision was performed. The real nature and the origin of the cyst is not elucidated.


Ectopic colonic epithelium of the bladder complicated by development of an adenocarcinoma.

A case of a female patient with an adenocarcinoma of the bladder emerging from ectopic colonic epithelium is reported. Although urothelial metaplasia in itself is not a premalignant lesion, patients with metaplasia of the bladder epithelium should be followed up very strictly since malignant degeneration has been proved to occur.


Endoscopic treatment of colovesical fistula. An endoscopical approach.

The authors report one case of a colovesical fistula in a 70-year-old man. The treatment was transurethral resection. There has been no evidence of recurrence in more than a two-year follow-up. This procedure could be useful when surgical treatment cannot be performed.


[Preliminary study of the hormonal effect on various parameters of the pelvic floor in genitally active women without hormone therapy and in menopausal women].

This study proves the benefit of estrogens on the laxity, tonicity and contractility of the pelvic floor, as measured with a tonimetric instrument. The statistical hypothesis, that these three parameters are improved in genitally active women during estrogenic phase as compared to the progestative phase, as well as in menopausal women under substitutive treatment as compared to the menopausal women without hormonal treatment, is confirmed with a high degree of significance.


[Treatment of prolapse using the abdominal approach].

Genital prolapses are regularly constituted by multiple disorders such as primary stress incontinence anterior and posterior colpocele enterocele. All of these must be taken into account during the treatment by abdominal approach. The principles of treatment consist into a fixation of prolapse with mersilene mesh to the promontory. It could be laid on the anterior wall of the vagina and sometimes on posterior, if it's necessary. Uterus could be preserved but subtotal or total hysterectomy might be done; in this case, aseptic conditions are absolutely imperative. Vaginal section with stapling instrument and absorbable staples is useful. A colpopexy is always made.


[S. Raz' method of bladder suspension and treatment of cystocele in urinary stress incontinence (short-term results)].

We performed the transvaginal approach described by S. Raz for stress urinary incontinence and cystocele. 13 patients with cystocele and stress urinary incontinence underwent the four corner Bladder neck suspension 12 patients with stress urinary incontinence alone underwent simple bladder neck suspension. After a median follow-up of 4,1 months 92% were cured of incontinence. Cystoceles grade II and III were completely reduced. These results are comparable with abdominal approach for less morbidity and shorter hospital stay.


HIV infection and rape.

We report the case of a woman who was found to be HIV positive after a sexual assault, in the absence of other risk factors for HIV infection. This observation and the report of one similar case support the view that HIV may be transmitted to a victim of a single sexual assault. We believe that all victims of rape should be offered a test for HIV and offered counselling. In addition to the current recommendations, the semen obtained should be tested for HIV antibodies by Western blot analysis. In the absence of clear data on safety and efficacy, we should recommend neither routine application of virucidal agents nor systematic Zidovudine (AZT) prophylaxis.


[Oral purine loading test for latent metabolic disorders of uric acid in patients with calcium containing upper urinary calculi].

For the detection of metabolic disorders of uric acid in upper urolithiasis, an oral purine loading test was performed in 78 patients with calcium-containing calculi, 5 patients with uric acid calculi, and 34 stone free subjects. From the results of the normal subject group, the criteria of hyperuricemia, latent hyperuricemia, hyperuricosuria and latent hyperuricosuria were proposed. In calcium-containing stone formers, 6 male patients showed hyperuricosuria, 18 male patients and 4 female patients showed latent hyperuricemia or latent hyperuricosuria. In uric acid urinary stone formers, all cases showed latent hyperuricemia or latent hyperuricosuria. These findings indicated that the metabolic disorders of uric acid might be one of the risk factors for the formation of calcium containing urinary stones, as well as uric acid urinary stones.


[Evaluation of kidney graft function with dynamic MRI--preliminary report].

The value of dynamic magnetic resonance imaging (MRI) in the examination of the function of transplanted kidneys was examined. Dynamic MRI was performed on 14 renal transplant patients. After the injection of Gd-DTPA (dimeglumine gadopentetate), we used small tip angle gradient echo (STAGE) technique with a flip angle of 20 degrees. The cortex was higher in signal intensity of well functioning grafts than the medulla before the injection in Gd-DTPA. Signal intensity of the cortex decreased after 30 seconds. After 1 minute the signal intensity of the cortex recovered and low intensity band meaning passage of Gd-DTPA at corticomedullary differentiation was displayed. Signal intensity of the medulla decreased after 3 minutes. Signal intensity of the parenchyma of transplanted kidney after 5 minutes was much the same as that before injection. Image of poor functioning grafts displayed unclear figures. Time-intensity values of both cortex and medulla in well functioning grafts decreased rapidly after about 2 minutes, and rose thereafter. Time-intensity curves of both cortex and medulla were almost flat on and after 5 minutes. Time-intensity curves of both cortex and medulla in poor functioning grafts were almost flat through out the examination. We concluded that effective parameters of the graft function for the time-intensity curve were delta I1 and delta I2. Dynamic MRI was suggested to be useful in the evaluation of kidney graft function.


[Treatment of endocrine-resistant stage D carcinoma of the prostate with a cisplatin derivative (DWA2114R): a pilot study].

DWA2114R (DWA) is a new derivative of platin compounds. Eleven patients with rapidly progressive, endocrine-resistant stage D carcinoma of the prostate were treated with infusion of DWA (800-1,000 mg/m2) every 3 to 4 weeks. A partial objective response was observed in 3 of 11 patients (27%). This response lasted from 5 to 11 months with an average of 7.7 months. Six patients (55%) had a significant decrease or disappearance of bone pain and five became ambulatory and asymptomatic. Four patients (36%) showed no change, and four patients (36%) did not respond to the treatment and showed progression of their disease. There were no patients with severe leukopenia (less than 1,000/mm3). No significant renal toxicity was observed in any of the patients and gastrointestinal toxicity was tolerable. DWA appears to be an effective drug available for the treatment of endocrine-resistant advanced carcinoma of the prostate.


[Clinical study of the epidermal growth factor contents in urine, plasma and tissue from the patients with urological diseases].

Contents of epidermal growth factor (EGF) in urine, plasma and tissues in urological diseases were estimated by enzyme immunoassay using beads bound to the anti-EGF antibody, and the clinical significance of the presence of EGF in the disease state was examined. There was no difference in EGF level between healthy male and female subjects (n = 22), and the level showed a tendency to decrease with age (p less than 0.05). The subjects were 19 cases of prostatic cancer, 7 of renal cancer, and 12 of urinary bladder cancer. The difference in EGF level between the healthy subjects and patients was not significant, and the levels were shown to be lower in 8 cases of renal insufficiency (including patients on hemodialysis:HD)(p less than 0.01). Plasma EGF levels in the 30 healthy subjects revealed no significant differences related to sex or age. Plasma EGF levels were lower in 42 cases of renal insufficiency (before and after HD), and in 7 cases of renal cancer (p less than 0.01); they ware significantly lower in 15 cases of prostatic cancer (p less than 0.05). In tissues including tumor sites, EGF levels were higher particularly in the prostatic gland tissue (hypertrophy and cancer regions). Thus, urinary and plasma EGF levels in urological diseases may be useful parameters of renal function, but its relationship with malignant diseases is still unknown. The EGF level should be explored in relation with the EGF receptor.


[A case of retroperitoneal teratoma showing high level of CA19-9].

We report a case retroperitoneal mature teratoma showing an abnormally high CA19-9 (carbohydrate antigen 19-9) serum level in a 30-year-old woman. She was hospitalized for an episode of left upper abdominal pain. High CA19-9 tissue level and immunohistochemical findings were found in removed tissue. This case is the third report of a CA19-9-producing teratoma and literature was reviewed and discussed.


[Bilateral adrenal metastasis from renal cell carcinoma].

A case of renal cell carcinoma with synchronous bilateral adrenal metastasis occurring in a 76-year-old woman is reported. In our case, preoperative computed tomographic evaluation revealed the presence of bilateral adrenal metastasis, and simultaneous right radical nephrectomy and contralateral adrenalectomy were performed. Pathological examination revealed renal cell carcinoma of right kidney metastasizing to both adrenal glands. Bilateral adrenal metastasis from renal cell carcinoma is rare. Our case seems to be the fourth case in the Japanese literature.


[Renal cell carcinoma with malignant peritoneal mesothelioma: report of a case].

We report a case of left renal cell carcinoma extending into vena cava with malignant peritoneal mesothelioma. A 41-year-old man presented to our outpatient clinic with macroscopic hematuria. Upon laparotomy, numerous white nodules were identified on diaphragm and serosa of liver, stomach, small intestine and mesentery. Biopsied specimen showed malignant mesothelioma of peritoneum and renal cell carcinoma of left kidney. He was treated with intraperitoneal cisplatinum and intravenous pirarubicin for mesothelioma, and chemoembolization for renal tumor. After two courses of therapy, he suffered from disseminated intravascular coagulation and died of subarachnoid hemorrhage. Autopsy revealed that intraperitoneal nodules were markedly decreased in number and renal tumor had changed into hemorrhagic necrosis, but tumor thrombus in vena cava had little necrotic change.


[Transitional cell carcinoma of the ureter with inverted proliferation: a case report].

A case of transitional cell carcinoma of the ureter with inverted proliferation is presented. A 74-year-old man with the chief complaint of asymptomatic macrohematuria was referred for a suspicion of a ureteral tumor. Excretory urography demonstrated a filling defect with a round smooth contour in the right lower ureter. Urine cytology was negative for malignant cells. No bladder tumor was noted by cystoscopic examination. Under the clinical diagnosis of a right ureteral tumor, right total nephroureterectomy was performed. The gross specimen contained a 2.0 x 1.0 cm, polypoid, pedunculated and smooth-surfaced tumor. The pathological diagnosis was transitional cell carcinoma with inverted proliferation G2 much greater than G1. Malignant tumor with inverted proliferation in the ureter is very rare. In Japan, 8 cases of transitional cell carcinoma with inverted proliferation in the ureter, including our case, are reviewed.


[Ectopic ureter opening to vestibule without urinary incontinence: a case report].

A case of a 2-year-old female with right ectopic ureter opening in vestibule vaginae and without urinary incontinence is reported. Excretory urogram showed mild dilatation of the upper right segment with bilateral complete duplication. Right ectopic ureter some functioning upper segment of the kidney was reimplanted into the bladder to avoid surgical intervention for heminephrectomy. According to the retrograde ureterogram of ectopic ureter the running courses and shapes of the dilated distal portions of ureters were compared between two groups, ectopic ureter with incontinence and that without incontinence. We suppose the continence mechanism of ectopic ureter is kept when the running course of the ureter through some portion of the urethral sphincter musculature.


[Male bladder leiomyoma: a case report].

A case of leiomyoma of the urinary bladder in a 40-year-old man is reported. Enucleation of the tumor was performed, because transurethral resection-biopsy revealed a bladder leiomyoma. Ninety nine cases of a bladder leiomyoma have been reported in Japan, but male cases are rare.


[Posterior urethral polyp: a recurrent case].

A 38-year-old man was admitted to our hospital complaining of difficult, frequent urination to our hospital. Transrectal echography and digital examination showed chronic prostatitis. He was treated with medication for chronic prostatitis but his condition did not improve. Retrograde urethrography revealed an obstructive change in the prostatic urethra and urethroscopic findings showed a urethral tumor in the posterior urethra. Transurethral resection of the tumor was performed. Pathological diagnosis of the urethral tumor indicated a urethral caruncle. After one year, the patient was readmitted to our hospital with the same complaints as before. Urethroscopic findings revealed the recurrence of a urethral polyp in the posterior urethra. Transurethral resection of the polyp was performed. Pathological findings revealed that the inner structure of the polyp showed a prostatic glandular pattern that after staining with anti-prostatic acid phosphatase antibody. The final diagnosis was that the polyp had a prostatic-type epithelium in the prostatic urethra.


[Clinical study of terodiline hydrochloride for the treatment of urinary frequency and urinary incontinence, and its cardiovascular adverse effects].

We evaluated the effectiveness and side effects of terodiline hydrochloride in 109 patients with urinary frequency and urinary incontinence. The drug was administered at a dose of 24 mg once a day or 12 mg twice a day for 4 weeks. Symptoms such as urinary frequency and urinary incontinence were alleviated in 101 out of 109 patients (92.7%). Mild side effects such as thirst, dysuria, sense of residual urine, orthostatic hypotension and arrhythmia were observed in 9 out of 109 patients (8.2%). Side effects such as orthostatic hypotension and arrhythmia were observed on the 28th day or the 20th day of the administration, but these symptoms disappeared with discontinued use of this medicine. The results obtained from this study suggest that terodiline hydrochloride may be greatly useful for the patients with urinary frequency and urinary incontinence. But we must take account of the side effects such as orthostatic hypotension and arrhythmia.


[The phase IV studies with Estracyt in prostatic cancer--supplementary report: results of long-term therapy].

Two hundred patients with prostatic cancer were enrolled in our previous study between 1984 and 1987. In this study, 96 patients of them were observed for 1 year or more after oral administration of Estracyt (estramustine sodium phosphate). Of these 96 cases, 33 patients were treated with Estracyt as primary treatment and 63 patient had been treated with other treatments before Estracyt treatment. Twelve patients were treated only with Estracyt and 84 patients also received other treatments. Thirty-eight patients were on primary therapy, 37 patients were on maintenance therapy, and 11 patients were on primary therapy, 37 patients were on maintenance therapy, and 11 patients were on the re-activated stage therapy and 10 patients were others. In conclusion, among the 67 cases in which the due judgement of the effect was possible, Estracyt was markedly effective in 10 cases (14.9%), effective in 16 cases (23.9%), slightly effective in 15 cases (22.4%) and ineffective in 26 cases (38.8%). The survival rate was 92.6% at the first year, 66.0% at the third year and 46.3% at the fifth year in the follow-up study. Adverse reactions were observed in 22 cases (22.9%), among which the administration was discontinued in 3 cases.


[The relationship between pathological spreading factors and tumor size in 45 patients with renal cell carcinoma].

The relationship between pathological spreading factors (T3,4 V+, N+, M+) and tumor size was studied in 45 patients with renal cell carcinoma during the past 10 years from 1982. The incidence of having one or more factors was 0% for the 17 tumors smaller than 5 cm, but 75% for the 28 tumors over 5 cm. The mean diameter of the tumors having a T, V, N or M factor was significantly larger than that of tumors having no factor (T1,2V0N0M0). These findings suggest that they have a higher tendency of having spreading factors once the tumors have exceeded a certain size.


[A clinical investigation on renal pelvic and ureteral tumors].

Sixty-six patients with renal pelvic and ureteral tumors were treated in our hospital between June 1974 and June 1991. These cases consisted of 27 renal pelvic tumors, 31 ureteral tumors and 8 renal pelvic and ureteral tumors. Their ages ranged from 43 to 86 years old (average: 65). There were 46 males and 20 females. The surgical method involved total nephroureterectomy with a cuff for 44 patients, nephroureterectomy for 3, nephrectomy for 9, total nephroureterectomy with total cystectomy for 5 and partial ureterectomy for 2. Histologically, there were 60 transitional cell carcinomas (TCC), 2 squamous cell carcinomas (SCC) and 4 TCC with SCC. As for the pathological stage, 13 were pTa, 16 pT1, 12 pT2, 11 pT3, 13 pT4 and 1 pTX. Subsequent bladder tumors were found in 13 patients (19.7%). The overall survival rate at 1, 3 and 5 years were 80%, 68% and 52%, respectively according to the Kaplan-Meier's method. In this series, the pathological staging was the most important prognostic factor.


[Transitional cell carcinoma of the upper urinary tract following total cystectomy for bladder cancer].

From 1975 to 1990, we treated 118 patients with urinary epithelial cancer, including 100 with primary bladder cancer, 13 with primary upper urinary tract cancer, and 5 with both diseases. Thirty-five patients with primary bladder cancer underwent total cystectomy. Upper urinary tract urothelial cancer developed in 4 patients (4.0%) and was detected only after cystectomy. Three patients had multiple bladder tumors before cystectomy and recurrent tumors under long-term bladder-preserving treatment. The other patient had had cystectomy for the primary bladder lesion. Our present policy is to perform urinary cytology once a month and intravenous urography once a year in patients with bladder cancer for early detection of secondary upper urinary tract cancer.


[Application of video endoscope system (EVIS200) in endourology].

We began clinical studies in April, 1989 for the purpose of utilizing the video endoscope system in the field of urology, termed the Urological Video Information System (UVIS). The UVIS is made up of an image assembling and recording system and an image filling system. Since we started using the first generation video endoscope system (EVIS-1, Olympus Optical Co.) as an image assembling system, we have encountered several major obstacles such as 1) the absolute insufficiency for the amount of light, and 2) the unclearness of frozen images. As we have been able to use as second generation video endoscope system (EVIS200, Olympus Optical Co.) since September 1990, the major components of the UVIS have been modified. In this report, we describe our clinical experience with the re-designed UVIS; EVIS200, which we have used, is composed of a video-processor (CL-200, Olympus Co.), a video converter and rigid urological scopes. The EVIS200 has been evaluated not only for the endoscopic examination but also for transurethral surgery. No problems were noticed in manipulating the EVIS200. Marked improvements were achieved in image quality. Images both on the television monitor and hard copies from the color video printer had optical quality in good agreement with the gross findings. The UVIS was a great contribution to both the authors and the patients; the findings both of the examination and the surgery could be explained to the patient and family during and/or immediately after the procedure. We believe that the UVIS may replace conventional urologic endoscopy and become an excellent date-base for endourology.


[A case of a child with extra-adrenal pheochromocytoma associated with renovascular hypertension].

A 7-year-old female was discovered to be severely hypertensive. Urinary noradrenaline excretion and plasma noradrenaline level were elevated. Plasma renin activity was markedly elevated. She was found to have a mass in the hilus of the left kidney and left renal artery stenosis. Magnetic resonance imaging (MRI) of the mass revealed an extremely bright lesion on T2 weighted image. DMSA renal scintigraphy revealed a low uptake rate (4.7%) in the left kidney. A diagnosis of extra-adrenal pheochromocytoma associated with left sided renal artery stenosis was made. The mass and left kidney were removed. Electronmicroscopic examination of the mass revealed characteristic neurosecretory granules. There was only slight fibrosis in the wall of the removed left renal artery.


[A case of retroperitoneal venous aneurysm].

A case of retroperitoneal venous aneurysm is reported. A 73-year-old woman was referred to us with the chief complaint of left abdominal mass. A giant abdominal mass was palpable and diagnostic imaging examination including ultrasound tomography, excretory pyelography, computed tomography, magnetic resonance imaging and angiography revealed a giant cystic mass encircled by calcification in the left retroperitoneal space. Operation for this cystic mass was performed under the preoperative diagnosis of a giant left renal cyst. During operation the mass was located between the left kidney and the left adrenal gland. Because it was difficult to separate the mass from the left kidney the mass was removed with the left kidney. The extirpated tumor measured 15.5 x 15.0 x 9.5 cm and contained old blood clots and red-yellow colored fluid. A histological examination revealed that the tumor wall was composed of smooth muscle and elastic fibers. Therefore, pathological diagnosis was retroperitoneal venous aneurysm. Retroperitoneal venous aneurysm is very rare. To our knowledge, this is the 8th case of retroperitoneal venous aneurysm reported in Japan.


[A case of retroperitoneal Castleman's disease associated with bladder tumor and a review of 59 cases in Japan].

We present a case of retroperitoneal Castleman's disease associated with bladder tumor. The patient was a 62-year-old man, who underwent partial cystectomy under a diagnosis of bladder tumor in 1989. Subsequently, recurrent bladder tumor was detected and he consulted the outpatient clinic at our University Hospital in November, 1990, at which time computerized tomography (CT) revealed a retroperitoneal tumor. From February, 1991 four courses of combined chemotherapy (methotrexate, vinblastine, pirarubicin, cisplatin) were administered for the tumor. The tumor reduction rate after the chemotherapy was 60% on CT, and retroperitoneal lymph node dissection and left nephroureterectomy were performed in July, 1991. Histological examination revealed Castleman's disease, hyaline-vascular type. Fifty-nine reported cases of retroperitoneal Castleman's disease in Japan are reviewed.


[A report of two cases of multilocular cystic renal cell carcinoma: review of 51 cases reported and the results of a prognostic survey].

We report 2 cases of multilocular cystic renal cell carcinoma. One was in a 33-year-old male, presenting with ultrasonic abnormality of the left kidney at an annual employee health care examination. Computerized tomography (CT) demonstrated a 5 cm of multilocular cystic mass adjacent to the lower pole of the left kidney. Another was in a 44-year-old male, presenting with microscopic hematuria at an annual employee health care examination. CT of the abdomen revealed a 6.5 cm of multilocular cystic mass on the upper pole of the right kidney. Both were diagnosed as renal cell carcinoma by the angiography and underwent radical nephrectomy. Gross specimens showed typical multilocular cystic appearance and histopathology showed clear cell carcinoma infiltrating septa and replacing epithelium of the cyst walls. Both patients are alive without evidence of disease at, 21 months and 14 months after operation, respectively. Including our cases, 51 multilocular cystic renal cell carcinoma and multilocular cystic nephroma associated with renal cell carcinoma have been reported. From the review of the literatures and the answer of the questionnaires inquiring about the outcome of the patient to Japanese reporters, the outcome of 38 patients was ascertained. The 10-year survival rates and non-recurrence rate after operation calculated by the Kaphan-Meier formula were 97.3% and 90.3%, respectively. Because of the good prognosis of reported cases, we concluded that we should choose kidney-sparing surgery for the operation of multilocular cystic renal cell carcinoma.


[Dilated cardiomyopathy following alpha interferon therapy of renal tumor with pulmonary metastases: a case report].

We report a case of renal cell carcinoma with pulmonary metastases treated with recombinant alpha interferon and subsequently presenting as congestive heart failure due to a dilated cardiomyopathy. A 66-year-old man presented himself to the department of internal medicine at our hospital with a complaint of persistent cough with sputum on August 27, 1988. Ultrasonogram, computed tomography and angiography showed a right renal cell carcinoma and chest x-ray films disclosed bilateral multiple nodular shadows, probably representing metastases of the renal tumor. After being transferred to our department, the patient underwent the ligation of the right renal artery and vein and the postoperative treatment with recombinant alpha interferon, achieving a complete response for pulmonary metastases and a partial response for the primary region. On February 14, 1990 the patient was admitted to our hospital with a complaint of dyspnea to be diagnosed as congestive heart failure due to dilated cardiomyopathy. The interferon therapy was suspected to have caused the heart disease, and four months after discontinuation of interferon therapy the heart failure symptoms had improved, but hypokinesis of the cardiac wall still persisted. To our knowledge, this may be the first case of alpha interferon-related cardiomyopathy in Japan.


[A case of renal cell carcinoma in childhood].

We report a case of renal cell carcinoma in a 6-year-old girl. The child had the chief complaints of gross hematuria and abdominal pain. An examination using ultrasound, computerized tomography scans and angiography showed a left renal tumor. Left side radical nephrectomy with lymphadenectomy was performed. Histopathological examination revealed renal cell carcinoma of clear cell type with metastasis to the hilar lymph node. She received postoperative therapy with interferon. Now, 3 years since the operation, she is living without evident recurrence. We reviewed 89 Japanese cases of renal cell carcinoma in children including this case and have discussed symptoms, differential diagnosis and treatments.


[A case of renal squamous cell carcinoma associated with giant hydronephrosis and ureteral stone: efficacy of imaging modality].

A rare case of squamous cell carcinoma of the right kidney associated with giant hydronephrosis and right ureteral stone was reported. A 60-year-old woman was referred to our department with a complaint of ileocecal dull pain. A plain computerized tomogram (CT) revealed giant hydronephrosis, and a kidney-ureter-bladder X-ray revealed a right lower ureteral stone. A right percutaneous nephrostomy was done and antegrade pyelography revealed giant hydronephrosis and a ureteral stone, but showed no intrapelvic filling defect. Under the diagnosis of right ureteral stone with hydronephrosis, right ureterolithotomy was done. However, since the inflammation did not subside after ureterolithotomy, right nephrectomy was done. The surgically removed right kidney did not show any evident tumor mass, a histological study revealed squamous cell carcinoma involving renal parenchyma. The patient received no adjuvant therapy and died 3 months after nephrectomy with sudden appearance of bone, liver and pulmonary metastases. The preoperative efficacy of imaging modalities for renal squamous cell carcinoma was discussed herein.


[Multiorgan failure following intravesical bacillus Calmette-Guerin administration: a case report].

We describe a case of multiorgan failure after intravesical bacillus Carmette-Guern (BCG) immunotherapy for bladder cancer. A 58-year-old man with superficial transitional cell carcinoma of the bladder was initially treated by transurethral resection and intravenous chemotherapy, and then administered 11 sessions of BCG intravesically. He was administered BCG intravesically after cystoscopic examination. The next day he complained of nausea and malaise. He became hypotensive. The symptom progressed with multiorgan failure, disseminated intravascular coagulation and respiratory failure. The patient gradually improved with administration of antibiotics and corticosteroid, and hemodialysis, without antituberculous antibiotics. Intravesical instillation of BCG should not be carried out immediately after cystoscopic examination.


[Pure leiomyoma of prostate presenting with rectal symptoms: a case report].

Pure leiomyoma of the prostate is a rare lesion. We report a case in a 68-year-old man who presented with rectal symptoms. Rectal examination showed a stony hard nodule with irregular surface near the apex of the prostate. Transrectal sonography showed a homogeneous well defined nodule measuring 3.5 cm in diameter in the left prostatic lobe protruding into the bladder. Magnetic resonance imaging (MRI) revealed an irregular shaped mass in the prostate with an isosignal to muscle in the T1 weighted images. Needle biopsy revealed pure leiomyoma histologically. Transurethral resection was performed and a nodule of white almost avascular tissue was resected in the apex proximal to vermontanum. After operation, the rectal symptoms improved.


[Traumatic dislocation of the testis].

Dislocation of the testis is a rare injury, with only 73 cases having been reported in Japan. We herein add 6 cases. Lately, accidents involving teenage patients, primarily involving motorcycles, have been increasing. Closed reduction is recommended, but it was successful only 5 of 73 cases. The results of testicular biopsies suggest that early surgical management is required when closed reduction is unsuccessful.


[Clinical statistics on inpatients admitted to the Department of Urology, Hyogo Prefectural Hospital Nishinomiya during 20 years from 1972 to 1991].

A statistic analysis was carried out on the 4,956 inpatients admitted to our Department of Urology from April 1972 to December 1991. The patients included 3,399 males and 1,557 females. A total of 4,105 operations including 255 renal allotransplantations were performed on 3,590 patients. Open surgery for upper urinary tract stones has been replaced by extracorporeal shock-wave lithotripsy (ESWL) in the last three years.


[Experimental urinary tract infection caused by Escherichia coli in diabetic mouse--uroepithelial colonization and polymorphonuclear leukocyte function].

Relationship between polymorphonuclear leukocyte (PMN) function and susceptibility to infections in diabetic mice was studied. In the experimental urinary tract infections, 6 strains of Escherichia coli with different fimbrial expression and hemolysin production were used. In contrast with non-fimbriated strains, fimbriated strains were more susceptible to phagocytosis by PMN. MS+.MR+ strains, however, showed resistance to intracellular killing by PMN. OEC-709, OEC-716 (MS+.MR+ strains), and OEC-734 (MS+.MR- strains), also showed resistance to the bactericidal activity of the serum. The killing activities of PMN derived from diabetic mice against these 3 strains were significantly lower than those of PMN from normal mice. In normal mice, MS+.MR+ strains showed the strongest colonization ability to the bladder and kidney, whereas MS-.MR- strains showed the weakest ability among the strains. In diabetic mice, the number of bacteria colonizing to the bladder and kidney was higher than that in normal mice, except for one MS-.MR- strain. Significant differences were observed in the strains (OEC-709, 716, 734), in which PMN was concerned strongly in the bacterial killing. Finally, these findings suggest that deterioration of the bactericidal activity of PMN in a diabetic state is involved in increased susceptibility of diabetic mice.


[Influences of bacteria within stones on ESWL treatment].

On 26 patients with upper urinary stones treated by extracorporeal shock wave lithotripsy (ESWL), the influences of the bacteria within the stones on the inflammatory complications, especially on urinary tract infection, after the ESWL treatment, were studied. The constituents of the stones obtained from these 26 patients consisted of the mixed stone of calcium oxalate and calcium phosphate (10 patients), calcium oxalate alone (2 patients), calcium phosphate alone (1 patient) and uric acid (1 patient). Of these 26 stones including no infection stones such as struvite and carbonate apatite, 5 stones (19.2%) had bacteria within the stone. Although no patients had severe inflammatory complications after ESWL treatments, the fact that the patient group having bacteria within the stones had a significantly elevated body temperature at one day after ESWL treatment compared to that on the preoperative day (P < 0.01) suggests that we should take into consideration the bacteria within non-infection stones as one of the risk factors of inflammatory complications after ESWL treatment.


Retroperitoneal neurilemoma: CT and MR findings.

Our objective was to characterize the CT and MR imaging findings of retroperitoneal neurilemomas. We reviewed the CT and MR imaging findings in six women with retroperitoneal neurilemomas. Retroperitoneal neurilemomas were round, 5-13 cm in diameter, and located in the presacral pelvic retroperitoneum in four patients and adjacent to the kidney in two patients. CT findings of the tumors were well-demarcated round masses showing prominent cystic changes and oriented in a somewhat radial fashion. Medium and heavily T2-weighted MR images showed high-intensity necrotic areas and nonnecrotic areas of various signal intensity. CT findings of a round mass with prominent cystic degeneration, along with certain MR imaging characteristics, may be helpful in the preoperative diagnosis of retroperitoneal neurilemomas.


MR imaging of the quadriceps tendon: normal layered configuration and its importance in cases of tendon rupture.

The quadriceps tendon is a multilayered structure with separate layers arising from different muscle groups. We examined this layered configuration on MR images to determine if it is relevant in the evaluation of the traumatized quadriceps tendon. Sagittal and axial T1-weighted MR images of 52 knees with normal tendons were reviewed to determine the number and the muscle origins of these layers. Five knees with traumatized quadriceps tendons were imaged with T1 and T2 weighting to determine the relationship between the layered configuration and the injury. All the normal quadriceps tendons had a laminated appearance with either four (6%), three (56%), or two (30%) layers. In 8%, the laminations were barely perceptible. The site of origin of each layer was consistent, and each favored a given muscle. The superficial layer originated from the posterior fascia of the rectus femoris muscle, and the deep layer originated from the anterior fascia of the midline vastus intermedius muscle. The middle layer(s) arose from the deep fascia separating the vastus medialis and the vastus lateralis muscles from the vastus intermedius muscle. When only two layers were present, the middle layer merged with the superficial and deep layers. In the injured tendon, complete rupture produced transection of all the layers. Incomplete ruptures were seen as focal discontinuities of individual layers; other layers remained intact. The existence of a layered configuration of the quadriceps tendon is significant in the MR examination of partial ruptures. It can help not only in detecting and localizing injuries but also in determining appropriate treatment based on the number or thickness of injured layers.


Relapsing-remitting multiple sclerosis: sequential enhanced MR imaging vs clinical findings in determining disease activity.

Sequential MR imaging frequently shows disease activity (clinically silent new brain lesions) in subgroups of patients with multiple sclerosis and therefore is valuable in monitoring the effects of treatment. Monitoring of disease activity in patients being treated for relapsing-remitting multiple sclerosis will increase in importance as new and safe therapies are developed. We studied sequential enhanced MR images of patients with early relapsing-remitting multiple sclerosis to define the MR features that indicate disease activity in this subgroup of patients and to compare MR imaging and clinical findings for this purpose. Seven patients with relapsing-remitting definite multiple sclerosis were examined monthly for 4-12 months. For each image, a standard repositioning protocol consisting of three images was used to ensure reproducibility of axial (double oblique) image planes, planned according to internal landmarks. A total of 58 unenhanced T2-weighted and enhanced T1-weighted MR images were obtained. MR images showed new enhancing lesions in six of the seven patients. On 25 (43%) of the 58 enhanced T1-weighted MR images, a total of 50 new enhancing lesions were observed, and on one image a reenhancing lesion was seen. The unenhanced T2-weighted images showed corresponding abnormalities for 92% of the new enhancing lesions. At follow-up, most lesions (86%) were enhanced on only one occasion: 4% were enhanced on more than two consecutive monthly MR examinations. Forty-nine percent of the lesions seen on T2-weighted images "disappeared" (beyond the resolution of the imaging system) after a mean follow-up of 3.5 months, especially lesions that were initially smaller than 5 mm. During the study, only five clinical relapses occurred in three patients (all at times when MR images showed contrast-enhancing lesions), and fixed disability did not increase. On 21 additional occasions, MR images showed new enhancing or reenhancing lesions in patients who were clinically stable at the time (4.2 times more clinically silent disease activity). Our results suggest that contrast-enhanced MR imaging is more sensitive than clinical monitoring for detecting new disease activity in patients with relapsing-remitting multiple sclerosis and that MR imaging might be useful in the evaluation of therapeutic regimens.


Evaluation of complex cystic masses of the brain: value of steady-state free-precession MR imaging.

This study evaluated the effectiveness of steady-state free-precession (SSFP) MR imaging of complex cystic masses of the brain compared with that of conventional T1- and T2-weighted spin-echo imaging. Our hypothesis is that SSFP MR images provide better characterization of these masses and facilitate more appropriate preoperative diagnoses and planning. Axial T1-weighted and SSFP MR images and specimens for pathologic examination were obtained in seven consecutive patients, 9-81 years old, with cystic mass lesions of the brain and neurologic symptoms and signs directly related to the masses. Axial contrast-enhanced T1-weighted images were obtained in six patients, surgical exploration was done in five patients, and stereotaxic biopsy was done in two. After examination of the routine spin-echo and SSFP images, the usefulness of SSFP images was determined by how well they facilitated correct preoperative diagnosis. On SSFP MR images, the solid or inhomogeneous components of a cystic mass had extremely low signals in contrast to the high signal of surrounding fluid. On routine spin-echo images, however, the signals of these components were masked by the signal of the surrounding fluid. SSFP MR images helped markedly in diagnosis of hemorrhagic, epidermoid, and arachnoid cysts. In cases of enhancing brain tumors, SSFP MR images provided the same information that contrast-enhanced images did. Overall, when SSFP MR imaging was used, more information about the texture and constituents of the cystic mass was obtained, and a more useful diagnosis was made. Initial results show that SSFP MR imaging is a more useful technique than conventional spin-echo imaging for characterizing complex cystic masses of the brain. SSFP MR imaging (1) allows distinction of edema from tumor, (2) helps establish where biopsy has the best chance of providing tissue that will show pathologic changes, and (3) helps distinguish simple cysts from tumors, tumor-cyst, or multicompartmental cyst and may be particularly helpful in detecting the contents of hemorrhagic cysts.


The value of cerebral angiography in predicting cerebral ischemia during carotid endarterectomy.

Temporary occlusion of the carotid artery during endarterectomy can result in ipsilateral cerebral ischemia if collateral blood flow is insufficient. This requires placement of a shunt across the carotid bifurcation, which is associated with increased operative risk. We retrospectively analyzed preoperative cerebral angiograms and intraoperative electroencephalographic recordings to determine if ischemia during carotid endarterectomy could be predicted from angiographic data. The cerebral angiograms of 30 patients were examined. Collateral blood flow to the hemisphere on the side of surgery was determined to be present if both proximal segments of the anterior cerebral artery and the anterior communicating artery were visualized, or if filling and washout of the ipsilateral posterior cerebral artery could be seen. Collateral flow was determined to be inadequate if the anterior collateral system was incomplete, and if either the ipsilateral posterior communicating artery was absent or the posterior cerebral artery filled without washout. This information was compared with intraoperative electroencephalographic and shunting data. Of 15 patients who had demonstrable collateral blood flow, 14 had stable electroencephalograms and did not require a shunt during surgery. In all 15 patients in whom no collateral flow to the ipsilateral hemisphere could be shown, electroencephalographic changes prompted placement of an intraluminal shunt. We found that the angiographic determination of inadequate collateral cerebral circulation correlated strongly with the development of intraoperative ischemia. This implies that routine preoperative cerebral angiograms can be used to alert the surgeon to the potential need for shunt placement during carotid endarterectomy.


MR imaging and HMPAO scintigraphy in conjunction with balloon test occlusion: value in predicting sequelae after permanent carotid occlusion.

Permanent occlusion of the internal carotid artery may be required for en bloc resection of a neck tumor or to treat certain aneurysms. The risk of ischemic infarct is usually assessed with carotid balloon test occlusion and concurrent distal arterial pressure measurement. However, up to 20% of patients who tolerate the test occlusion have delayed neurologic sequelae. We propose enhanced MR imaging and hexamethylpropyleneamine oxime (HMPAO) scintigraphy to detect subclinical signs of ischemia and hypoperfusion as adjuncts to the balloon test occlusion to identify patients at risk for delayed sequelae. We prospectively examined 12 patients referred for balloon test occlusion of the carotid artery. Serial measurements of distal occluded internal carotid pressure were recorded. 99mTc-HMPAO was injected IV after 2 min of asymptomatic test occlusion, and single-photon emission computed tomographic (SPECT) data acquisition was done 1-6 hr later. Contrast-enhanced MR imaging was performed 1-8 hr after completion of the 30-min test occlusion. Signs of decreased perfusion or ischemia on these tests were compared with the mean distal arterial pressure and neurologic status of the patient during test occlusion. Seven (58%) of 12 patients had abnormal findings on HMPAO scintigraphy or contrast-enhanced MR imaging. Only one patient had neurologic deficits that corresponded to abnormal MR enhancement. The other 11 patients (92%) remained asymptomatic during the 30-min test occlusion. Of these 11 asymptomatic patients, five (45%) had areas of decreased perfusion on scintigraphy and three (27%) had abnormal MR contrast enhancement suggesting residual focal ischemia as a result of the test occlusion. Mean arterial pressures in the distal occluded artery did not correlate well with the imaging results. HMPAO scintigraphy can show clinically silent areas of decreased perfusion, while enhanced MR shows signs of acute ischemia (i.e., significant hypoperfusion) associated with asymptomatic balloon test occlusion. Theoretically, such patients would be at increased risk for permanent sequelae after permanent carotid occlusion.


MR imaging of clival and paraclival lesions.

A wide spectrum of diseases involve the clivus and paraclival structures. Primary neoplasms, metastatic tumors, and inflammatory, vascular, and hematopoietic disorders are the most common abnormalities to arise from or directly involve the clivus. MR imaging exquisitely shows and helps characterize the diseases that affect this area. Sagittal and coronal MR imaging allows precise localization and evaluation of the signal characteristics of a mass, enabling a more specific diagnosis. The multiplanar capabilities of MR imaging provide superb visualization of the adjacent cranial nerves and vascular structures, aiding in surgical planning and radiation therapy. In this pictorial essay, the MR imaging, CT, and conventional radiographic findings of various clival and paraclival lesions are illustrated.


Femoral artery pseudoaneurysms: value of color Doppler sonography in predicting which ones will thrombose without treatment.

The purpose of this study was to evaluate the Doppler imaging characteristics of femoral artery pseudoaneurysms occurring after cardiac catheterization to determine if color Doppler sonography can be used to predict which pseudoaneurysms would ultimately thrombose spontaneously. Over a 30-month-period, 24 pseudoaneurysms were studied with serial color Doppler sonography. The color flow, B-mode, and Doppler spectral images and clinical records of patients whose pseudoaneurysms demonstrated spontaneous thrombosis were compared with those of patients who required surgical repair of the pseudoaneurysm. We found no statistically significant differences between the patients whose pseudoaneurysms demonstrated spontaneous thrombosis and those treated surgically in regard to clinical parameters or the volume of the pseudoaneurysm, percentage of flow within the pseudoaneurysm, ratio of forward to reversed flow velocity in the pseudoaneurysm neck, duration of diastolic flow in the pseudoaneurysm neck, or length of pseudoaneurysm neck. However, on color Doppler images, the volume of flow in the lumens of pseudoaneurysms that thrombosed spontaneously (1.8 +/- 3.3 ml) was significantly smaller than the volume of flow in the lumens of those treated surgically (4.4 +/- 3.2, ml, p = .02). We conclude that pseudoaneurysms with small volumes of flow in the lumen are more likely to thrombose than are those with large volumes of flow in the lumen. However, color Doppler sonographic characteristics cannot be used to predict subsequent thrombosis.


Closure of the ductus venosus in neonates: findings on real-time gray-scale, color-flow Doppler, and duplex Doppler sonography.

Our objective was to document the anatomy, flow pattern, and time of closure of the ductus venosus in healthy full-term neonates. We examined the ductus venosus in 73 neonates by using gray-scale sonography, color flow imaging, and duplex Doppler sonography. Each neonate was examined 1-2 days after birth, 6-7 days after birth, and then every 3-4 days until closure was confirmed or the neonate was 18 days old. The length, width, and color flow and duplex Doppler characteristics of the ductus were noted. Closure of the ductus at 6-7 days after birth was examined with respect to birth weight, hemoglobin level, and gestational age. The ductus venosus, extending from the left portal vein to the inferior vena cava, was identified with all three techniques. The ductus was patent in all 73 neonates 1-2 days after birth. It was still patent in 41 (68%) of 60 neonates reexamined 6-7 days after birth and in two of three neonates (11% [7/60]) reexamined 17-18 days after birth. Blood flow within the ductus was cephalic, in a constant venous waveform. Initial flow velocity ranged from 0.15 to 0.70 m/sec and decreased consistently in subsequent examinations. There was no significant difference in birth weight, hemoglobin level, or gestational age between the group whose ductus was closed and the group whose ductus was open at 6-7 days after birth. The ductus venosus in neonates is consistently detectable on sonography. It is patent in a greater percentage of neonates, and for a longer time, than was previously shown with conventional radiographic studies with angiography.


Giant fistula between the right coronary artery and the left ventricle: diagnostic significance of right posterior oblique chest radiograph.

Congenital coronary artery fistulas are uncommon. The prevalence of coronary artery fistulas in adults has been estimated as 0.13% [1]. Most of these fistulas communicate with the right atrium or ventricle or with the pulmonary artery; those emptying into the left atrium or ventricle are quite rare [2, 3]. Usually, patients with coronary artery fistula do not have clinical symptoms, and their chest radiographs do not show the corresponding shadow because the fistula is hemodynamically insignificant. When the fistula is large, however, chest radiographs show the secondary hemodynamic changes, such as cardiac enlargement or increased pulmonary vasculature, depending on the emptying site. Moreover, the silhouette of the dilated tortuous vessel itself can be seen on the chest radiograph. We have examined four patients, each of whom had a giant fistula in the right coronary artery emptying into the left ventricle, proved by coronary angiography. In this essay, we illustrate the chest radiographs of these patients and describe the radiologic features that permit a specific diagnosis or suggest a coronary artery fistula.


Needle-tip localization during CT-guided abdominal biopsy: comparison of conventional and spiral CT.

This study was performed to determine whether the time required for needle-tip localization during biopsy of the abdomen would be reduced if continuous-volume data acquisition, also known as spiral CT, were used for guidance instead of conventional CT. Forty patients had biopsies of an abdominal mass; half underwent needle-tip localizations with conventional CT and half with spiral CT. The times required to localize the needle for 104 needle passes were calculated; scanning and reconstruction times were included, and the radiologist's technique and procedural difficulties were deliberately excluded. The mean needle localization times with conventional and spiral CT were compared for the upper abdominal and pelvic regions by using the two-tailed unpaired Student's t-test. The mean time (+/- SE) for spiral CT was 35 +/- 2 sec compared with 105 +/- 18 sec for conventional CT (p < .001). When analyzed by region, times with spiral CT were shorter in both the upper abdomen (means, 37 sec for spiral CT vs 150 sec for conventional CT, p < .001) and pelvis (means, 25 sec for spiral CT vs 74 sec for conventional CT, p = .038); the magnitude of the improvement was greater in the upper abdomen. The time required to find the needle tip during guided biopsy of an abdominal mass is reduced with spiral CT compared with conventional CT. This improvement is partly a result of the ability to eliminate respiratory misregistration with spiral CT, which is not possible with conventional multisectional CT; hence the greater advantage in upper abdominal biopsy.


Digital archive center: implementation for a radiology department.

In this article, we describe the implementation of a digital archive center for a radiology department in a 700-bed teaching hospital. The archive center consists of two identical archive systems, each comprising five components: an archive server, a data-base server, an optical disk library, a stand-alone optical disk drive, and a communication network. An image management system controls the image traffic from acquisition devices to display stations. A fault-tolerant mechanism was built into the archive center to achieve a 100% uptime. The center has been in operation for over 6 months. We have not experienced a single total system failure during this period. It currently archives all digital images from three MR units and four CT scanners and selected images from three computed radiographic systems and two laser film digitizers. The center archives between 1.5 and 2.0 gigabytes of images per workday. With its built-in fault-tolerant mechanism, we believe that the implemented archive center is very reliable and is suitable for a radiology department to archive its digital images.


Evaluation of congenital heart disease with MR imaging: current and coming attractions.

Nearly 10 years of experience in the use of MR imaging for the diagnosis of congenital heart disease has accumulated. Although MR imaging is superior to other techniques in showing certain structures and abnormalities such as small central pulmonary arteries in tetralogy of Fallot, aortic coarctations, and venous connections in heterotaxia syndromes, it remains an ancillary tool to echocardiography and cardiac catheterization. In this review, we examine present limitations and advantages of conventional MR in the evaluation of congenital anomalies of the heart and great vessels and explore future developments that might bring MR imaging into the diagnostic mainstream. Key improvements now in development are ultrafast MR systems for acquisition of multiple real-time MR images (in 30 msec or less) and on-line three-dimensional computer reconstruction of the heart and great vessels. Improved display and understanding of complex anatomy, as well as more extensive functional analysis of hearts before and after surgery, should be the benefits of such developments.