Number of positive lymph nodes independently affects long-term survival after resection in patients with ampullary carcinoma.

AIM: The nodal status is an established prognostic factor in ampullary carcinoma. The aim of this study was to compare the prognostic power of the anatomic location of positive nodes with that of the number of positive nodes. METHODS: Of 73 consecutive patients treated for ampullary carcinoma, 62 underwent pancreaticoduodenectomy with regional lymphadenectomy. A survival analysis of these 62 patients by nodal status was conducted retrospectively. A total of 1942 lymph nodes taken from the patients were examined histologically for metastasis. The location of positive regional nodes was classified into 4 categories, according to the Japanese staging system. The number of positive regional nodes was recorded for each patient. The median follow-up period was 124 months. RESULTS: Nodal disease was found in 31 patients, of whom 23 had 1-3 positive regional nodes and 8 had >or=4 positive regional nodes. Univariate analysis revealed that both the location (p<0.0001) and the number (p<0.0001) of positive nodes were significant prognostic factors. Multivariate analysis revealed that the number of positive nodes was an independent prognostic factor (p=0.007), while the location failed to remain as an independent variable. The median survival time was 59 months with a 5-year survival rate of 48% in patients with 1-3 positive nodes, whereas all patients with >or=4 positive nodes died of the disease within 29 months of resection (p=0.0001). CONCLUSION: The number, not the location, of positive regional lymph nodes independently affects long-term survival after resection in patients with ampullary carcinoma.

Subclinical vestibulo-cerebellar, anterior cerebellar lobe and spinocerebellar effects in lead workers in relation to concurrent and past exposure.

By computerized static posturography, the subclinical effects of past and concurrent lead absorption on the vestibulo-cerebellum (lower vermis), anterior cerebellar lobe and spinocerebellar afferent pathway were examined in 49 male chemical factory workers exposed to lead stearate (lead workers). Their concurrent blood lead (BPb) concentrations ranged from 7 to 36 (mean 18.0) microgram/100 g. In the past, their maximum BPb ranged from 11 to 113 (mean 47.7) micrograms/100 g; mean BPb was 7-52 (mean 23.5) micrograms/100 g; and cumulative BPb, defined as mean BPb x years of exposure, was 15-1268 (mean 390.6) micrograms.year/100 g. Control subjects were 23 healthy male workers who had never been occupationally exposed to lead. The postural sway of high (2-4 Hz) and low (1 Hz or less) frequencies with eyes open for lead workers was significantly greater than that for controls in the medio-lateral (right-left) and anterior-posterior directions. Similarly, the sway of high and low frequencies with eyes closed was significantly larger in lead workers than in controls in the medio-lateral direction. Results of stepwise multiple regression analysis indicated that the sway with frequencies of 0.5-2 Hz with eyes open was related to concurrent BPb in the anterior-posterior direction. With eyes closed the sway of high frequency was significantly related to mean BPb in the past in the medio-lateral direction. The pattern of the changes suggests that the vestibulo-cerebellum, anterior cerebellar lobe and spinocerebellar pathway are asymptomatically affected by lead. It appears that the change in the vestibulo-cerebellum reflects concurrent lead absorption, while on the other hand, that in the anterior cerebellar lobe reflects past lead absorption.

Alcohol and the oculomotor system.

The influence of alcohol on the oculomotor system was observed by means of the caloric eye tracking pattern (CETP) test, the visual suppression test on caloric nystagmus, and the positional nystagmus, eye tracking and gaze nystagmus tests. In Group A (nine cases whose CETP before the intake of alcohol was normal), the influence of alcohol consumption appeared regularly and consistently in the following order: abnormality of CEPT greater than or equal to positional alcohol nystagmus greater than or equal to abnormality of the eye tracking pattern greater than or equal to alcohol gaze nystagmus. On the contrary, in Group B (eight cases whose CETP before the consumption of alcohol was already abnormal), with one exception, the regularity noted in Group A was not observed. This phenomenon may be attributable to the presence of latent disorders of the oculomotor system. In both groups, the duration of the caloric nystagmus itself was slightly shortened and its amplitude somewhat suppressed after the consumption of alcohol. The results were confirmed by experiments in which the subjects kept their eyes open in darkness. On the other hand, when the eyes were kept open in light surroundings, the duration and amplitude of the caloric nystagmus were exaggerated in appearance because the mechanism of visual suppression was disturbed by alcohol.

Equilibrium disorder in carbamazepine toxicity.

Three cases of acute carbamazepine intoxication were evaluated neurotologically and neurologically. Findings included symptoms of equilibrium, gait and speech disorders, drowsiness, gaze nystagmus, depressed optokinetic nystagmus and disturbances of smooth pursuit eye movement. These findings, suggestive of a space-occupying lesion, disappeared after the cessation of the medication. On the basis of the clinical findings it is felt that carbamazepine affects structures within the brain stem and the cerebellum. It is well known that equilibrium disorders caused by anticonvulsant intoxication are due to cerebellar disorders, but from our present study it should be noted that they originate not only from cerebellar lesions but also from brain stem lesions.

Caloric-eye tracking pattern test: I. Visual suppression and the possibility of simplified differential diagnosis between peripheral and central vertigo.

During the examination of patients who complain of vertigo or who have equilibrium disorders, it is often difficult to determine the etiology of the disorders, that is, to determine whether it is dependent on a peripheral or central vestibular disorder. To attempt to guess the etiology in these cases, we devised a new method: the caloric eye-tracking pattern test. In normal subjects and in patients with peripheral disorders, as is well known, caloric nystagmus has little influence on the eye-tracking pattern. In contrast, in patients with central vestibular disorders, caloric nystagmus evoked abnormalities on the eye-tracking pattern, either superimposed or saccades, in spite of the fact that the eye-tracking pattern before the caloric stimulation is normal. These findings result from the visual suppression mechanism to the vestibular nystagmus. We can say that the visual suppression to the vestibular nystagmus is evoked more strongly bu pursuing a moving visual stimulus than by gazing at a stationary target. These results are interesting, not only form the physiological view point, but also from the clinical view point. There is a possibility of the differential diagnosis between peripheral and central vertigo.

Leptospiral antigens in the liver of experimentally infected guinea pig and their relation to the morphogenesis of liver damage.

In order to investigate the morphogenes of experimental leptospirosis by morphologic and immunohistologic methods, 24 guinea-pigs were inoculated intraperitoneally with L. interrogans serogroup Icterohaemorrhagiae. They were divided in 6 groups, sacrificed from the 1st to the 6th day of infection. Semiquantitative analyses of histopathological liver lesions were performed in 1 micron sections of tissue embedded in glycol-methacrylate. The distribution of leptospiral antigen (L. Ag) and its glycolipoprotein (GLP) was demonstrated by peroxidase-antiperoxidase on paraffin embedded tissue. Significant lesions appeared at the 4th day of infection, progressing to a peak on the 6th day. Inflammation was associated with injury of the portal triad. Liver cells showed either swelling or acidophilic degeneration and necrosis, together with loss of cell cohesion, leading to disarray of liver cell plates. Mitochondria were found progressively enlarged and irregularly distributed. L. Ag expression was parallel to the morphological changes. Portal distribution was significant at the 4th day and on later stages centrilobular localization became predominant. Spiral forms suggestive of intact leptospires were initially found but, chiefly at the 6th day, L. Ag was seen in granules, probably resulting from phagocytosis. GLP staining was similar to granular L. Ag in morphology, and distribution. Cytokeratin condensation was seen in liver cells with acidophilic necrosis and was marked in areas of disorganization of cell plates. Our findings lead us to hypothesize a direct leptospiral cytotoxic effect on endothelial and on liver-cell membranes. At first, leptospires themselves would induce subcellular changes acting mainly on membrane permeability. Afterwards, their granular forms, including GLP, would act as adjuvant factors. These findings demonstrate that the disarray of liver cell plates at the late phase of the disease is genuine.

[The serovars of Leptospira interrogans isolated from cases of human leptospirosis in São Paulo, Brazil]. / Sorovares de Leptospira interrogans isolados de casos de leptospirose humana em São Paulo, Brasil.

Eighteen strains of L. interrogans isolated from human cases were serotyped by the agglutinin-absorption test at Instituto Adolfo Lutz in São Paulo, Brazil. Fourteen were identified as serovar copenhageni (icterohaemorrhagiae serogroup), 2 as canicola (canicola serogroup), 1 as castellonis (Ballum serogroup) and 1 as pomona serogroup (serovar not yet defined). The frequency of serovar copenhageni in 100% of the isolates in icterohaemorrhagiae serogroup is emphasized and more studies to verify the real serovars prevalence as subsidy to the epidemiology of this infection are suggested by the authors.

[An evaluation of the ELISA-IgM test in the early diagnosis of human leptospirosis]. / Avaliação do teste ELISA-IgM no diagnóstico precoce da leptospirose humana.

Thirty-seven sera samples from patients with leptospirosis icterohaemorrhagic form were studied with a time interval of 2 to 12 days between the beginning of the symptoms and the collection blood samples. It was isolated leptospira of 5 patients' hemocultures (13.5%) and from 4 of these the etiological agent pertained to the serogroup Icterohaemorrhagiae serovar copenhageni. Thirty-five of them (94.6%), including the four patients whose the etiological agent was isolated, showed reactivity in the enzyme linked immunosorbent (ELISA) IgM test. By this way, it was demonstrated that this test is important for a rapid diagnosis of human leptospirosis, even in the beginning of the disease, when there is still leptospiraemic phase.

[Evaluation of counterimmunoelectrophoresis with antigens of icterohaemorrhagiae and patoc serovars in the serodiagnosis of human leptospirosis]. / Avaliação da contraimunoeletroforese com antígenos dos sorovars icterohaemorrhagiae E patoc no diagnóstico sorológico da leptospirose humana.

Counterimmunoelectrophoresis (CIE) was applied on paired sera from 135 patients with leptospirosis and on 69 sera from a control group. The sera from patients were subdivided in 4 groups according to the results obtained by the Microscopic Agglutination Test (MAT). The first samples sera from 58 patients were non reagent by MAT. Six monthly samples of sera were taken from 7 patients to follow-up and to determine the level of agglutinin and precipitin antibodies present using MAT and CIE. Serovars icterohaemorrhagiae and patoc were used as antigens. Three types of antigens were compared, 1) Triton-X-100 extracted; 2) heat extracted and 3) a pool of them. The CIE using icterohaemorrhagiae derived antigens types agreed with MAT in 92.64, 92.64 and 94.11% of the leptospirosis sera. The patoc antigens types reacted with the control group in 7.24, 86.95 and 84.05% of the samples, and consequently were eliminated from the present study. The icterohaemorrhagiae CIE reaction become positive earlier than MAT negative sera, and reverted to negative earlier in the follow-up samples from the patients. The CIE was sensitive and specific, gave rapid results and was easy to perform.

[Outbreak of human leptospirosis by recreational activity in the municipality of São José dos Campos, São Paulo. Seroepidemiological study]. / Surto de leptospirose humana por atividade recreacional no município de São José dos Campos, São Paulo. Estudo soroepidemiológico.

An outbreak of human leptospirosis due to recreational activities occurred at São José dos Campos, São Paulo, Brazil in November 1987. It involved a group of persons who had participated in a gathering in a suburb club which had a swimming pool fed with natural water. Epidemiological investigation was carried out and laboratory tests from the patients were done. It was observed that a high prevalence of the pomona serotype (91%) was found in the serological analyses, while the presence of the agent of the infection could not be found in the water club swimming pool.

[Immunodiagnosis of human leptospirosis by ELISA-IgM, employing different antigenic preparations from prevalent serovars of Leptospira interrogans]. / Imunodiagnóstico da leptospirose humana através do teste ELISA-IgM, empregando-se diferentes preparações antigênicas a partir de sorotipos prevalentes de Leptospira interrogans.

A comparative study among different serovars of Leptospira interrogans was performed in order to prepare antigens to detect IgM antibodies by ELISA in early and late phase of human leptospirosis. Ten serovars were chosen among the most prevalent detected by microscopic seroagglutination (SAM) in São Paulo city. Using ELISA-IgM five of them showed better results (canicola, hebdomadis, icterohaemorrhagiae, cynopteri and brasiliensis). These ones were also studied in a pool. The non-treated antigens showed higher reactivity than the Triton X-100 (4%/50 degrees C/4h). ELISA-IgM using individually or pool of non-treated antigens proved to be reliable with high sensitivity and should be used for an earlier diagnosis of leptospirosis, as a trial test. Faster diagnostic elucidation can be useful to detect epidemic situations, so, allowing epidemiological surveillance interventions.

[Glycoproteins from Leptospira interrogans serogroup icterohaemorrhagiae: distribution in the liver and kidney of experimentally infected guinea pigs]. / Glicolipoproteína de Leptospira interrogans sorogrupo icterohaemorrhagiae: distribuição em fígado e rim de cobaias experimentalmente infectadas.

Tissue damage in leptospirosis has been ascribed to direct effect of the microorganisms and/or their virulence, including products synthetized by leptospires or released during their lysis. This study aimed at chemical extraction of the glycolipoprotein (GLP) from virulent leptospires, production of a rabbit anti-GLP and analysis of its distribution in liver and kidney of inoculated guinea-pigs, sacrificed sequentially from the 1st to 6th day of infection, covering the whole, spectrum of acute leptospirosis. The comparison of GLP expression to local injuries aimed at new pathogenetic data. GLP was detected in liver and kidney in 2 out of 6 guinea-pigs on the 5th day and in all 6 animals on the 6th day of infection. Granular forms were seen in the cytoplasm of macrophages, free in interstitium or adhered to endothelial and parenchymal cell membranes, especially in the most damaged sites. These findings lead us to the hypothesis of GLP as a toxic factor resulting from leptospiral lysis by macrophages. Although it was not proved as a promoter of initial lesions, it seems to be related to the enhancement of tissue damage late in the course of the disease.

[Therapy of tinnitus. Tympanic cavity infusion of lidocaine and steroid solution]. / Therapie des Ohrensausens. Paukenhöhleninfusion von Lidocain- und Steroidlösung.

Tinnitus is an otological symptom which is often encountered and is yet difficult to treat. If tinnitus is of cochlear origin then it seems reasonable to assume that a total depression of the cochlear function will abolish cochlear tinnitus. To achieve this depression, transtympanic injections of a local anesthetic (4% Lidocaine) to anesthetize the inner ear and of Decadoron were conducted in a patient suffering from tinnitus. One hundred and sixty-eight patients (220 ears) who had suffered from relatively long-term tinnitus were included in this study. In almost all of the cases the clinical symptoms and the otological findings (i.e., the audiogram and caloric test) indicated that the probable lesion underlying the tinnitus was located within the end organ. In some cases this injection brought a transient (for few days), slight, neurosensorial deafness in the low-frequency range. This auditory disorder, however, was completely restored without sequelae. Our results are summarized as follows: in 76 ears, tinnitus was abolished completely, in 109 ears, tinnitus was considerably ameliorated, in 35 ears, tinnitus was slightly ameliorated or no effect. One hundred and nine patients (138 ears) who had suffered from tinnitus were included in this study. Decadoron was applied to the middle ear cavity by transtympanic injection. Our results are summarized as follows: in 87 ears, tinnitus was abolished, in 39 ears, tinnitus was considerably ameliorated, in 14 ears, tinnitus was slightly ameliorated or no effect.

[Classification of optokinetic after-nystagmus and its topographical-diagnostic significance in man]. / Die Klassifizierung des optokinetischen Nachnystagmus (optokinetic after nystagmus, OKAN) und seine topisch-diagnostische Bedeutung beim Menschen.

The existence of optokinetic after-nystagmus (OKAN) has long been known, as far back as the age of Bárány. The term OKAN means nystagmus appearing after first inducing optokinetic nystagmus, and then the optokinetic stimulation is removed. It appears easily with the eyes open in a dark place. There have been various theories about the mechanism of the onset of OKAN. Sakata et al. previously classified the types of OKAN into the following 7 types: 1) The normal type, (2) the directional preponderance type, (3) the disinhibitory type, (4) the inversive type, (5) the inhibitory type, (6) the dysmetric type, (7) the clonic type. In the present study, the authors performed a vestibular equilibrium function inspection, including an OKAN inspection, on about 10,000 patients who visited the Department of Neuro-Otology with complaints of vertigo and equilibrium disturbance. The results of the inspection were classified in accordance with Sakata's method, and the diagnostic contribution of the OKAN inspection was examined. The diagnostic significance of the OKAN inspection is considered as follows: (1) This inspection can detect a very small difference between the left and right of nystagmus in the vestibular-optokinetic system, which difference cannot be detected with OKP inspection giving a rather strong stimulation or with the caloric test giving a non-physiological strong stimulation. (2) This can be a focal localization diagnostic method by the classification by type.

[Treatment of Ménière's disease. Middle ear infusion with lidocaine and steroid solution]. / Behandlung der Ménièreschen Krankheit. Paukenhöhleninfusion von Lidocain- und Steroidlösung.

Before considering the surgical treatment of patients with Ménière disease who would resist to various conservative therapies, including oral drug therapy, the author experimented the inner ear anesthetic therapy or the middle ear infusion therapy with a steroid solution, and each therapeutic result was compared. The results were as follows: 1) The effectiveness of the inner ear anesthetic therapy for vertigo was noted in 42 ears out of the total 47, while the effectiveness of the middle ear steroid infusion therapy for vertigo was found in all treated 21 ears. 2) Although both therapies proved non-effective for hearing disturbance, excluding special cases, the former therapy was found effective for it in 26 ears among 42. 3) For other concomitant symptoms such as the full sensation of ear obturation, head heaviness, and stiff shoulders, both therapies were considerably effective. It was concluded from these results that the first choice of therapy for patients with Ménière disease who should resist to all conservative therapies should be the middle ear steroid infusion therapy at the out-patient clinic, and the second choice would be the inner ear anesthetic therapy, and that both therapies were worth while experimenting before considering surgical treatment.

Early diagnosis of acoustic neuroma (1989) after experience of 37 cases.

Although the diagnosis of acoustic neuroma as classically described is generally thought to be easy, this is not always true for this so-called "ear tumor" which is localized within the internal auditory meatus. Recently, remarkable progress has been made in the diagnostic instrumentation and operative techniques used to treat acoustic neuroma, emphasizing the need for early diagnosis so that treatment can take place earlier than before. Through early diagnosis, some cases of total resection of acoustic neuroma have recently become possible, with preservation of not only facial nerve function, but preservation of auditory function as well. In the present report, we outline the early diagnosis of acoustic neuroma by summarizing 37 cases of acoustic neuroma experienced at our institution. We discuss historical presentations, and laboratory tests used in diagnosis including pure tone audiometry, speech audiometry, auditory brainstem evoked response (ABR), vestibular caloric stimulation, and computed tomography (CT) enhanced by introduction of air into the posterior fossa. Two representative cases are also presented. It should be emphasized that no clinical test is 100% sensitive or specific, and attention must be paid to chronological discrepancies in the patient's presentation and "cookbook"-type approaches to evaluation should be avoided.

Positional nystagmus of benign paroxysmal type (BPPN) due to cerebellar vermis lesions. Pseudo-BPPN.

Positioning nystagmus accompanied by severe vertigo had been reported in patients with partial lesions of the inner ear, especially otolith lesions. Typically this type of nystagmus represents a latent period and subsequent fatiguability. We concur with this finding and have constantly emphasized the significance of this phenomenon in clinical diagnosis. Since we started to use CT-scanning, this type of nystagmus has been noted in 20 patients, all of whom had cerebellar vermis lesions. Attention should be focused on this association. A simple coincidence could not be excluded if such a combination were seen in only 1 or 2 patients, it could be attributed to simple coincidence. But its occurrence in as many as 20 patients a causal role of cerebellar vermis lesions. Its mechanism may be explained by incomplete inhibition of the vestibulo-oculomotor system including the cerebellar flocculonodular lobe or vestiburo-cerebellum.

Directional preponderance of optokinetic nystagmus. Study of 30 cases of unilateral cerebral lesions.

Analysis of the optokinetic nystagmus has been one of the most important means to examine the function of the vestibulo-oculomotor system. Especially in Japan, it has been used as a mean to analyze the function of the brain stem. We investigated directional preponderance of the optokinetic nystagmus in supratentorial lesions especially unilateral lesions, in the cerebral hemisphere which had been nearly neglected as an object for investigation of the vestibular system. We examined 30 cases of unilateral lesion in the cerebral hemisphere. In all cases CT-scan confirmed that these lesions have no mass effect which might affect the function of the surrounding brain. It was also confirmed that these cases had no spontaneous nystagmus. These cases consisted of 11 cerebral infarctions, 9 cerebral thrombosis, 6 cerebral hemorrhages and 4 cerebral contusions. In the result, 27 cases showed directional preponderance of the optokinetic nystagmus to the ipsilateral side, while there was none to the contralateral side. Three cases showed no directional preponderance. Some cases showed marked inhibition of optokinetic nystagmus of the contralateral side. These markedly inhibited cases are very similar to cases of pontine lesion which usually manifest marked inhibition of the optokinetic nystagmus to the ipsilateral side.

Sylvian aqueduct syndrome. Chronology of tumors in the pineal region in view of ocular movement.

We experienced 21 cases of tumors (13 of pinealoma of the two-cell pattern and eight of tumors originating from the posterior part of the third ventricle). We carefully observed the eye movements of these patients during their respective clinical courses and found changes in abnormal eye movements along with remission following cobalt irradiation therapy or ventriculo-peritoneal shunt as well as with relapse on recurrence of tumors. From the neurotological viewpoint, we divided the development of these abnormal eye movements into four chronological stages. We emphasized the importance of the early diagnosis of tumors manifesting Sylvian aqueduct syndrome. Careful observation and analysis of eye movement will be a great help in making diagnoses as well as decisions for further examination and treatment.

Pathophysiology of positional vertigo of the malignant paroxysmal type.

It is well known that paroxysmal positional vertigo is induced by change of head position and subsides immediately when the head is returned to the original position. There are two types of paroxysmal positional vertigo. One is what DIX and HALLPIKE (1952) call the benign type which is thought to be caused by otolith lesions. Another is a malignant type, in contrast to the former and is related to a lesion in the central nervous system. Otologists are usually familiar with the former, but the latter is not known among neurologists and neurosurgeons. We experienced 37 cases of the malignant type and found that this type of paroxysmal vertigo is induced by various diseases. Furthermore, we believe that the mechanism of this paroxysmal vertigo is the lack of inhibitory function of the vestibular cerebellum, and not abrupt malfunction of communication of the cerebrospinal fluid in the ventricular system. We also believe that this symptom is a very useful sign for diagnosing lesions of the cerebellar vermis.