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.

Special features of old age vertigo.

In daily clinical practice, it is seen that elderly patients complain most frequently of dizziness, tinnitus, and hearing loss. Listening to those complaints, do we not tend just to attribute them to age? Against this background, we review vertigo in elderly patients briefly and consider the key points of its treatment. In comparison to younger people, what is first noticeable about elderly people is that they have a lot of fat in the body and a markedly low level of intracellular water. In other words, elderly people are always at risk of dehydration and liable to enter a shock state. The dorsal root in the elderly is also degenerated, and this explains such diverse complaints as dizziness, tinnitus, ringing in the head, headache, neck and shoulder stiffness, and lumbago. However, these complaints cannot be dismissed simply as "an unidentified syndrome." Behind these complaints is invariably one or another organic disorder. This is the conclusion we have reached from our day-to-day clinical practice.

Treatment of cochlear tinnitus with transtympanic infusion of 4% lidocaine into the tympanic cavity.

Tinnitus is an otological symptom that is encountered often, yet its treatment is difficult. If tinnitus is of cochlear origin, a reasonable assumption is that a total depression of the cochlear function will abolish cochlear tinnitus. To achieve this depression, transtympanic infusion of a local anesthetic (4% lidocaine) to anesthetize the inner ear was conducted in a patient suffering from tinnitus. Transtympanic infusion of 4% lidocaine was performed as a treatment for cochlear tinnitus, and its efficacy was investigated. The overall efficacy rate for the 292 patients with 369 affected ears was 81%. In the investigation of the treatment results in cases of different underlying ear diseases, the efficacy rate was high for tinnitus accompanying sudden deafness and labyrinthine vertigo. However, vestibular symptoms, such as vertigo and nausea, developed after lidocaine infusion. No permanent side effects were noted. Lidocaine infusion is thought to be a useful treatment option for tinnitus and should be considered before surgical treatment. Inner ear anesthesia into the tympanic cavity has been carried out in patients who had cochlear tinnitus and in whom conservative methods of therapy, such as oral medication, had proved unsuccessful. This treatment method is useful as a local therapy for cochlear tinnitus.

Caloric eye-tracking pattern test: 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, often identifying the etiology of the disorders is difficult (i.e., determining whether it is dependent on a peripheral or a central vestibular disorder). To attempt to determine 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 in the eye-tracking pattern, either superimposed or as saccades, despite the fact that the eye-tracking pattern before caloric stimulation was normal. These findings result from the visual suppression mechanism to vestibular nystagmus. We can conclude that the visual suppression to vestibular nystagmus is evoked more strongly by pursuing a moving visual stimulus than by gazing at a stationary target. These results are interesting, not only from the physiological viewpoint but from the clinical viewpoint. The differential diagnosis should include both peripheral and central vertigo.

Postural sway frequency analysis in workers exposed to n-hexane, xylene, and toluene: assessment of subclinical cerebellar dysfunction.

To clarify the effects of organic solvents on the postural balance system, 29 male sandal, shoe, and leather factory workers exposed to n-hexane, xylene, and toluene (solvent workers) were examined by computerized static posturography with sway frequency analysis. Concentrations of metabolites of solvents in urine samples taken from the workers in the morning before work ranged from 0.41 to 3.06 (mean, 1.20) mg/g creatinine (Cn) for 2,5-hexanedione, from 0.10 to 0.43 (mean, 0.19) g/g Cn for methylhippuric acid, and from 0.05 to 2.53 (mean, 0.37) g/g Cn for hippuric acid; estimated concentrations of n-hexane in workplace air ranged from 13 to 100 (mean, 40) ppm. Control subjects were 22 healthy males without exposure to solvents. With eyes open, postural sway with a frequency of 2-4 Hz in solvent workers was significantly larger than that in controls in the anteroposterior direction. With eyes closed, sway with a frequency of 0-1 Hz was significantly larger in solvent workers in the mediolateral and anteroposterior directions. Results of multiple regression analysis showed that with eyes open the 1- to 2-Hz and 2- to 4-Hz sways were related positively to 2,5-hexanedione and inversely with methylhippuric acid. The pattern of changes suggests that the vestibulocerebellar and spinocerebellar afferent systems are asymptomatically affected by n-hexane; the effect of n-hexane on the vestibulocerebellar system is possibly inhibited by xylene.

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.

Clinical Experiences of Steroid Targeting Therapy to Inner Ear for Control of Tinnitus.

We summarize our long-term clinical experiences with an inner-ear drug delivery system (DDS) for control of tinnitus. The inner-ear DDS consist of transtympanic perfusion of 2 or 4 mg dexamethasone to the round window via the middle ear. Therapeutic results of steroid targeting therapy to the inner ear were evaluated in 3,978 ears of 3,041 patients. Tinnitus improved in 75% of these patients immediately after treatment and in 68% after 6 months. The effects of such therapy on tinnitus varied depending on the underlying diseases. The improvement of tinnitus in the presence of labyrinthine hydrops was good, whereas the effects on noise- or drug-induced tinnitus were poor. Our results indicate that in high-tone tinnitus, the effects were poor, but they were good for low-pitched tinnitus. No correlation existed between the efficacy of management and loudness of the tinnitus. The dangers of perforating the eardrum and of inciting the discomfort of vertigo as a result of the transtympanic injection of dexamethasone are minimal. We believe that the transtympanic infusion technique is an effective DDS for control of inner-ear diseases and symptoms. This technique may be performed by any neurootologist in an outpatient clinic.

[Neurotological examination of patients with alcohol dependency].

This study was performed in 37 patients with alcohol dependency. The mean age was 46.3 years and mean duration of heavy drinking was 23.8 years. The mean duration of temperance to the initial examination was 21.4 days and that to the second examination was 82.0 days. The results of the test on body sway in patients with alcohol dependency may summarized as follows. In patients with alcohol dependency the length of and the area covered by the body sway were significantly larger than in the normal group (p < 0.05). This significant difference from the normal group disappeared open eyes, but remained with eyes closed (p < 0.05). The Romberg quotients of both the length and the environmental area tended to be larger than the normal group mean (p < 0.05). The oscillation power spectrum obtained with eyes open and that obtained with eyes closed tended to be low at levels below 0.2Hz and high at range of 0.2Hz to 0.5Hz in the right left direction. The power spectrum in the anterior-posterior direction obtained with eyes closed was lower than that in the normal group at levels less than 0.2Hz, and higher than that in the normal group at range of 2.0Hz to 3.0Hz on the first examination. After temperance on the second examination, these significant differences had disappeared at all levels. The results of the present study on ocular movements in patients with alcohol dependency may be summarized as follows. Using the oculomotor test, abnormalities appeared in more than 40% of the test subjects for ETT, OKN, OKAN, VS and lateral gaze nystagmus test. According to the report of Matsuoka in 1979, some head positional nystagmus was noted in about 30% of patients with alcohol dependency. In the present study, the rate of appearance was as low as 8%. Ataxic pursuit, vertical positioning nystagmus, decrease of VS, disturbance of OKN and abnormalities of OKAN were found. These results suggested lesions between the brain stem and cerebellum, especially around the upper and lower vermis of cerebellum. After about 3 months of temperance, each test revealed a tendency towards some improvement, but the disturbance appeared to be fixed in some cases. It was important that some improvement in the oculomotor and the central vestibular system was found after about 3 months temperance. These results are quite promising for treatment and recovery in patients with alcohol dependency.

Treatment of Cochlear-Tinnitus with Dexamethasone Infusion into the Tympanic Cavity.

Intratympanic dexamethasone infusion was performed as a treatment for cochlear-tinnitus and its efficacy was investigated. This is a Steroid Targeting Therapy (STT) for cochlear-tinnitus. The overall effective rate for the 1214 patients with 1466 affected ears was 71%. In this study, cochlear tinnitus was seen frequently in the age group of 50 - 60 years old, a relatively older population. The results of the treatment for tinnitus in different age groups did not show a correlation between age and efficacy rate of treatment. In the investigation of the treatment results with different underlying ear diseases, the efficacy rate was high for tinnitus accompanying chronic otitis media, Ménière's disease, and labyrinth syphilis. The efficacy rate tended to decrease more with longer disease duration. When the mean hearing level and treatment results were evaluated, a high effective rate was found in patients who had mild deafness. The efficacy rate was high in tinnitus of low tone pitch, and low tinnitus with high tone pitch. On the other hand, different degreees of loudness of tinnitus did not correlate with treatment effects. This treatment method is useful as a local therapy for cochlear-tinnitus in an outpatient setting.

Use of the visual suppression test using post-rotatory nystagmus to determine skill in ballet dancers.

Twelve ballet dancers with various levels of dancing experience and skill were examined with the visual suppression test using post-rotatory nystagmus (PRVST) and caloric stimulation (CVST). The PRVST results showed a suppression rate that was higher than in untrained subjects. The CVST results showed a suppression rate similar to that in untrained subjects. A correlation between the PRVST and CVST suppression rates and the length of dancing experience showed that the suppression rate increased as the level of experience and skill rose. These results indicate that the PRVST and CVST can aid in the clinical and quantitative assessment of the function of the central nervous system in visual-vestibular interactions in ballet dancers. Additionally, testing may have determined function of vestibulo-cerebellar pathways through habituation of visual-vestibular interactions. Findings indicate that it may be possible to use suppression rates of PRVST and CVST to determine the approximate level of a dancer's experience and skill.

Search for agglutinating antibodies to Leptospira and Leptospira and Leptonema in horses, Sao Paulo, Brazil

Soros de 922 equinos aparentemente sadios, mantidos na Fazenda do Instituto Butantan (Säo Roque, SP) para produçäo de soros hiperimunes, foram analisados quanto à presença de anticorpos para sorovares de Leptospira interrogans e para Leptonema illini, através da reaçäo de aglutinaçäo microscópica (MA). Entre os 807 (87,5 por cento) animais positivos, 659 (81,7 por cento) reagiram com mais de um sorovar, com títulos entre 1:100 e 1:6.400, havendo predomínio de títulos baixos (<= 1:400), 84 por cento dos soros positivos reagiram com representantes do sorogrupo Icterohaemorrhagiae e 79,2 por cento com Leptonema illini. Dos 23 sorovares utilizados, apenas o tarassovi näo reagiu

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.

Detection of leptospiral antigen (L. interrogans serovar copenhageni serogroup Icterohaemorrhagiae) by immunoelectron microscopy in the liver and kidney of experimentally infected guinea-pigs.

Guinea-pigs were experimentally infected with L. interrogans serovar copenhageni serogroup Icterohaemorrhagiae and their liver and kidney were studied by immunoelectron microscopy using the post embedding indirect immunogold labelling technique. Primary antibody was a purified rabbit anti-serum produced against the same leptospiral strain used in the inoculum. Gold-labelled leptospiral antigen (LAg) was found close to cell membranes of hepatocytes, kidney tubular cells and endothelial cells of the interstitial capillaries of the kidney. Afterwards it was internalized by hepatic and tubular cells, and eventually found in lysosomes. Phagolysosomes of Kupffer cells were also found to contain remnants of degraded leptospires and gold-labelled LAg. Gold-labelled intact leptospires were detected at the enlarged intercellular spaces between hepatocytes at the areas of hepatic cell plate disarray, showing the potential for leptospiral migration during the septicaemic phase of the disease potentially contributing to the pathogenesis of the lesions. The affinity of leptospiral antigenic material for cell membranes suggests an initial interaction with cell surface proteins followed by its internalization and cell damage. The nature of antigenic material detected, however, remains undefined; it may be a toxin, an enzyme or any other factor/s involved in leptospiral virulence.

Antigens involved in the human antibody response to natural infections with Leptospira interrogans serovar copenhageni.

Serum samples from patients with leptospirosis were screened by the microscopic agglutination test (MAT), ELISA and by immunoblotting. The latter two tests were performed with L. interrogans serovar copenhageni isolated from human blood culture. Immunoblotting with patients' sera revealed antibodies recognizing several leptospiral components in the molecular weight range 14.5-105 kDa of both IgM and IgG response. All patients' serum samples presented IgM antibodies reacting with a diffuse band of mol. wt of 14.8-22 kDa proteinase-K resistant and most reacted with bands of 26.5-28.7, 38-39 and 43-43.5 kDa. The IgG response appeared to be at variance. Examination of sequential serum samples obtained over a 4-8-month period revealed little change in the profile of antigen recognized after the 40th day of infection. Sera from healthy individuals presented IgM antibodies reacting with several leptospiral antigens, but lacked response against those of diffuse band of 14.8-22 kDa.

[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.

[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.

[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.

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

Positioning nystagmus accompanied by severe vertigo has been reported in patients with partial lesions of the inner ear, especially otolith lesions. Typically, this type of nystagmus shows 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 using CT-scanning, this type of nystagmus has been noted in 47 patients, all of whom had cerebellar vermis lesions. Attention should be focused on this association; if such a combination were seen in only 1 or 2 patients, it could simply be attributed to coincidence. But its occurrence in as many as 47 patients indicates 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 vestibulo-cerebellum.

Visual suppression test using post-rotatory nystagmus. Clinical course in patients with motion sickness.

With the results of VS test (%) we were able to classify patients into three groups as follows: Group I, hyper range of visual suppression, VS (%) = 100-90; Group II, normal range of VS (%) = 89-45; Group III, reduced or abolished range of VS (%) = less than 44. The results with VS test using post-rotatory nystagmus (PRN) were in Group I 58 cases, in Group II 28 cases and in Group III 1 case, and using caloric nystagmus (CN) the results in Group I were 39 cases, Group II 29 cases, and Group III 1 case. With the correlation of VS test between PRN and CN we were able to classify patients into four types as follows: Type I, hyper range of VS in both PRN and CN; Type II, hyper range of VS in PRN; however, normal range of VS in CN; Type III, normal range of VS in both PRN and CN; Type IV reduced or abolished range of VS in both PRN and CN. It was very interesting in the clinical course of motion sickness that patients under 11 years of age (18 cases) of Type I (31 cases) showed marked improvement to Type III (11 cases) at the time of disappearance of symptoms; however, patients over 12 years of age (13 cases) of Type I remained stationary Type I (9 cases) at the time of disappearance of symptoms.