A Case of Glucagonoma with Liver Metastasis: Complete Response to Dacarbazine

Abstract: We report a case of glucagonoma syndrome with liver metastasis, who responded completely to dacarbazine chemotherapy. A 77-year-old woman complained of itching skin eruptions (diagnosed as necrolytic migratory erythema) and weight loss. She was found to have glucose intolerance, anemia, hypoproteinemia and hyperglucagonemia. Abdominal CT and celiac arteriography showed a hypervascular tumor in the pancreatic tail and a metastatic tumor in the left hepatic lobe. Immunohistochemical examination of the metastatic liver tumor obtained by laparoscopic biopsy revealed the tumor cells to be positive for glucagon. The patient was treated with 20 courses of 300 mg/day intravenous dacarbazine for 5 consecutive days followed by a 4 week drug-free interval. No major side effects were noted. Treatment resulted in disappearance of the skin lesions and correction of anemia, glucose intolerance, hypoproteinemia and hyperglucagonemia. Follow-up abdominal CT showed complete resolution of both the primary pancreatic tumor and the metastatic liver tumor. We suggest that dacarbazine be considered as the treatment of choice for metastatic glucagonoma.     

Detecting herpesvirus DNA in uveitis using the polymerase chain reaction.

BACKGROUND: Herpesviruses are involved in the pathogenesis of many ocular diseases including keratitis, iridocyclitis, and acute retinal necrosis syndrome. The rapid and accurate diagnosis of herpetic infections has become increasingly important with the rising incidence of immunosuppressive diseases. The purpose of this study was to evaluate the use of the polymerase chain reaction (PCR) to detect herpesvirus DNA in uveitis patients. METHODS: Aqueous samples were aspirated from 11 patients with active uveitis of suspected viral origin. Using PCR, masked samples were assayed for herpes simplex virus (HSV), varicella zoster virus (VZV), and cytomegalovirus (CMV) to assist in supporting the clinical diagnosis of viral aetiology. Masked controls included 10 aqueous humour specimens from normal patients undergoing cataract surgery and specimens from seven patients diagnosed with active non-viral uveitis--Behçet's disease, sarcoidosis, Fuchs' heterochromic iridocyclitis, or Harada's disease. RESULTS: Ten of 11 cases clinically diagnosed as being of possible viral aetiology yielded aqueous PCR positive for a herpesvirus. Eight patients were PCR positive for amplified HSV DNA, of whom two had acute retinal necrosis, one had corneal endotheliitis, and five had recurrent iridocyclitis. VZV DNA was detected in one case of iridocyclitis, and CMV DNA in one case of chorioretinitis. Successful therapy was based on the PCR results. Ten normal aqueous specimens and the seven uveitis samples from cases not suspected of a viral aetiology were PCR negative for HSV, VZV, and CMV. CONCLUSION: These results demonstrate that detecting herpesvirus DNA in the aqueous humour is useful to support a clinical diagnosis of viral uveitis.     

Gerstmann-Sträussler syndrome — A variant type: amyloid plaques and Alzheimer's neurofibrillary tangles in cerebral cortex

Summary This report presents a variant of Gerstmann-Sträussler syndrome (GSS). A 53-year-old female had developed slowly progressive dementia and atactic gait since the age of 45. No myoclonic jerks and periodic synchronous discharges were observed throughout the illness. The neuropathological study revealed that many amyloid plaques and widespread Alzheimer's neurofibrillary tangles (NFTs) appeared in the cerebral cortex. Characteristically, the plaques reacted with anti-prion protein and none of them reacted with anti- protein, and they were made of many components, including amyloid cores, macrophages laden with lipid granules and/or degenerated neurites. Neuropil threads were seen mainly in amyloid plaques. Moreover, plaques appeared which were confluent and laminar in arrangement in the fifth and sixth cortical layers and had a close relationship to the neuronal loss. There was no spongiform change in the cerebral cortex or cerebellum. The cerebellum was almost intact except for a few amyloid plaques. Ultrastructurally, some of the plaques simulated kuru plaques and others had many degenerated neurites possessing paired helical filaments and other accumulated organelles. GSS has been proposed to include cases with progressive ataxia, dementia and massive multifocal plaques in the brain with or without cerebral spongiform changes. The case presented here is a very peculiar case of GSS. Recently, similar cases have been reported in some large families, diagnosed as familial Alzheimer's disease. These cases may be a telencephalic form with numerous NFTs of GSS.     

Influence of sinus impulses on the parasystolic cycle length

Recently, it has been shown that in most clinical cases of parasystole, the parasystolic rhythm is not completely independent of the sinus rhythm. In this study, to disclose the mechanism of such "irregular" parasystole, parasystolic cycles with an intervening sinus QRS complex (XSX) were compared with their immediately adjacent pure parasystolic cycles without any intervening nonparasystolic QRS complexes (XX) in 10 cases of ventricular parasystole. In eight cases, the XSX interval was equal to or nearly equal to the adjacent pure XX interval; in one, the XSX interval was shorter than the XX interval; and in only one, the XSX interval was longer than the XX interval. In six cases in which the XSX interval was almost equal to the XX interval, calculated XSX intervals with a later intervening sinus QRS complex were obtained from the differences between the XSSX interval (ie, interectopic interval with two intervening sinus QRS complexes) and its adjacent XX interval. In five of the six cases, the calculated XSX interval was shorter than the XX interval. These observations suggest that in most cases of parasystole, early intervening sinus impulses do not change the parasystolic cycle, whereas late intervening sinus impulses shorten the parasystolic cycle. This suggests the presence of type I second-degree entrance block as the mechanism of "irregular" parasystole.     

Intracranial hemorrhage associated with aplastic anemia

Intracranial hemorrhage is a fatal complication associated with aplastic anemia. We have encountered four patients who experienced six episodes of intracranial hemorrhage (intracerebral hemorrhage; 3, subarachnoid hemorrhage; 2, and subdural hematoma; 1,). Intracranial hemorrhage occurred without traumatic episodes, and was followed by frequent hemorrhagic episodes in other parts of about one year duration. This disease is considered to recur after a short interval. The site, type and degree of intracranial hemorrhage varied, and therefore intracranial hemorrhage seemed to be caused not only by thrombocytopenia but also by multifactorial hemorrhagic tendency. Transfusion of platelet rich plasma, and administration of Glycerol and steroids produced good results for conservative therapy. Continuous spinal drainage for subarachnoid hemorrhage was a relatively safe and useful means of management. In the patients who showed precipitous deterioration, the CT scan findings indicated that the high-density-area was diffusely spread with an unclear border, just like "contusional hemorrhage". For such severe cases, blood evacuation with craniotomy and emergency splenectomy are considered to be valuable.     

"My hand" sign associated with tactile extinction in two patients with callosal lesion

Two patients with "my hand" sign in association with tactile extinction from callosal lesion, one due to left anterior cerebral artery occlusion, the other due to right anterior cerebral artery aneurysm rupture, were reported. The examination of "my hand" sign was performed with the methods proposed by Brion et al. Our patients correctly responded when they grasped their own or the examiner's thumb with their left hand. But they replied "my finger"when they grasped not only their own but also the examiner's thumb with their right hand. Left tactile extinction was observed after a routine extinction test in one patient, and it was observed in the other after the following method: both patient's index fingers were disposed in his midline position. In these methods of extinction test, they made errors in saying "right" when both fingers were touched simultaneously. However, they said "both" when their right index finger alone was touched (synchiria) during an extinction test using the following method: both index fingers of patients were approached by examiner to touch each other or for one of them to touch the examiner's finger. When they were asked whose finger they touched in this method (whose finger test), they made the same errors as seen in "my hand" sign test. These test results suggest that there is a common underlying mechanism in the "my hand" sign and extinction, because the sense of double stimulations felt when only one stimulation is given (synchiria), is a possible explanation for the "my hand" sign and the pathogenesis of synchiria appears to be related to extinction.(ABSTRACT TRUNCATED AT 250 WORDS)     

In vivo activity on murine tumors of a novel antitumor compound,N-β-dimethylaminoethyl 9-carboxy-5-hydroxy-10-methoxybenzo[a]phenazine-6-carboxamide sodium salt (NC-190)

Summary A novel antitumor compound, N--dimethylaminoethyl 9-carboxy-5-hydroxy-10-methoxybenzo[a]-phenazine-6-carboxamide sodium salt (NC-190) was evaluated for its antitumor activity in experimental murine tumor systems. In the initial studies with P388 leukemia (i.p.-i.p.), NC-190 led to an increase of >200% in life span (ILS), and 75% of the mice were alive on day 30, when the optimal dose (50 mg/kg, days 1–5) was given. Additionally, the compound had significant activities against i.p. inoculated mouse L1210 leukemia, B16 melanoma, M5076 reticulum cell sarcoma, sarcoma 180, mouse hepatoma MH134, and rat Yoshida sarcoma and Yoshida ascites hepatoma AH130. The optimal dose resulted in a >280% ILS with a 30-day survival of 50% in mice with L1210 leukemia (100 mg/kg, days 1–5), a 156% ILS in mice with B16 melanoma (50 mg/kg, days 1–5), a 98% ILS with a 90-day survival of 25% in mice with M5076 reticulum cell sarcoma (25 mg/kg, days 1, 5, 9, and 13), a >300% ILS with a 60-day survival of 50% in mice with sarcoma 180 (50 mg/kg, days 3–10), a 148% ILS with a 60-day survival of 25% in mice with MH134 (25 mg/kg, days 1–5), a 129% ILS with a 60-day survival of 12.5% in rats with Yoshida sarcoma (12.5 mg/kg, day 3–10), and a >161% ILS with a 60-day survival of 50% in rats with AH130 (6.3 mg/kg, days 3–10). In the experiments with s.c. inoculated tumors, NC-190 not only inhibited tumor growth, but also increased the life span of mice with Lewis lung carcinoma or B16 melanoma. The 60-day survivors accounted for 60% and 30% in mice with Lewis lung carcinoma and B16 melanoma, respectively. The compound significantly inhibited the spontaneous lung metastasis of Lewis lung carcinoma by more than 90% when eight daily i.v. injections were given. NC-190 was active by the i.p., s.c., and i.v. routes. Five consecutive daily i.p. doses (days 1–5) were more effective than a single dose (day 1), two doses (days 1 and 5), or three doses (days 1, 5, and 9). NC-190 warrants further study as a potential antineoplastic agent against human neoplasms, as it has a broad spectrum of antitumor activity and inhibits metastasis.Abbreviations ILS increase in life span - MST median survival time - MMC mitomycin C - ADM adriamycin - CPA cyclophosphamide - 5-FU 5-fluorouracil     

Recent Trends in the Treatment and Prognosis of Adult Leukemia with Characteristics of Patients in Japan: Transition during the Fifteen Years from 1971 to 1985

Patients with acute (2,569) and chronic (957) leukemia diagnosedat 19 institutes took part in the study on the "MultidisciplinaryTreatment of Leukemia" between 1971 and 1985 and were investigatedretrospectively. By dividing the 15 years into three five-yearperiods, we were able to compare patient ratios in the differentperiods. The proportions of acute to chronic leukemia casesshowed no obvious change; however, the proportions of casesdiagnosed as acute lymphocytic leukemia in acute leukemia showeda significant increase. The main chemotherapeutic drugs usedduring the three time periods were cytarabine or its analogues,the anthracyclines, 6-mercaputopurine and prednisolone, againstacute myelogenous leukemia, and the vinca alkaloids, prednisoloneand the anthracyclines against acute lymphocytic leukemia. Therate of complete remission from acute myelogenous leukemia mademarked progress, from 45.1% during 1971–1975 to 62.3%during 1981–1985, but that of acute lymphocytic leukemiashowed no significant progress, being 65% during 1971–1975and 69.7% during 1981–1985. The durations of remission,however, and the survival times for patients with acute lymphocyticleukemia, as well as for those with acute myelogenous leukemia,became significantly longer over the three periods. Median survivaltimes from chronic myelocytic leukemia were 37–40 mo inall three periods, showing no progress. There was a better prognosisin cases of chronic myelocytic leukemia with, than without,Philadelphia chromosome. Except for a low incidence of chroniclymphocytic leukemia in Japan, adult leukemia patients' characteristicsand prognoses seem to be almost the same in Japan as in theU.S.A. and Europe.     

Identification of 16 novel mutations in the argininosuccinate synthetase gene and genotype-phenotype correlation in 38 classical citrullinemia patients

Classical citrullinemia (CTLN1), a rare autosomal recessive disorder, is caused by mutations of the argininosuccinate synthetase (ASS) gene, localized on chromosome 9q34.1. ASS functions as a rate-limiting enzyme in the urea cycle. Previously, we identified 32 mutations in the ASS gene of CTLN1 patients mainly in Japan and the United States, and to date 34 different mutations have been described in 50 families worldwide. In the present study, we report ASS mutations detected in 35 additional CTLN1 families from 11 countries. By analyzing the entire coding sequence and the intron-exon boundaries of the ASS gene using RT-PCR and/or genomic DNA-PCR, we have identified 16 novel mutations (two different 1-bp deletions, a 67-bp insertion, and 13 missense) and have detected 12 known mutations. Altogether, 50 different mutations (seven deletion, three splice site, one duplication, two nonsense, and 37 missense) in 85 CTLN1 families were identified. On the basis of primary sequence comparisons with the crystal structure of E. coli ASS protein, it may be concluded that any of the 37 missense mutations found at 30 different positions led to structural and functional impairments of the human ASS protein. It has been found that three mutations are particularly frequent: IVS6-2A>G in 23 families (Japan: 20 and Korea: three), G390R in 18 families (Turkey: six, U.S.: five, Spain: three, Israel: one, Austria: one, Canada: one, and Bolivia: one), and R304W in 10 families (Japan: nine and Turkey: one). Most mutations of the ASS gene are "private" and are distributed throughout the gene, except for exons 5 and 12-14. It seems that the clinical course of the patients with truncated mutations or the G390R mutation is early-onset/severe. The phenotype of the patients with certain missense mutations (G362V or W179R) is more late-onset/mild. Eight patients with R86H, A118T, R265H, or K310R mutations were adult/late-onset and four of them showed severe symptoms during pregnancy or postpartum. However, it is still difficult to prove the genotype-phenotype correlation, because many patients were compound heterozygotes (with two different mutations), lived in different environments at the time of diagnosis, and/or had several treatment regimes or various knowledge of the disease.     

Reaction products of diphenyl sulfide with formaldehyde. Formaldehyde resins. 98

The acid-catalyzed condensation of formaldehyde and diphenyl sulfide was carried out in benzene in the presence of p-toluene sulfonic acid. From the products, four poly(methylene diphenyl sulfides) of the following structures were isolated.