Cerebral infarction and high serum levels of muscle-derived enzymes associated with abrupt increase in hematocrit in a patient with secondary erythrocytosis]

A 70-year-old man was admitted to our hospital because of fever and progressive dyspnea in December 1989. He was already diagnosed as having erythrocytosis secondary to pulmonary fibrosis 4 years previously and the values of his hematocrit (Ht) were maintained between 44.5 and 62.9% by repeated phlebotomy. Immediately after admission, severe diarrhea developed and the Ht value was 61.5%. Around 1:30 a.m. of the 3rd hospital day, he developed disturbance of consciousness. In addition, the serum levels of LDH, CPK, aldolase, and myoglobin of muscle origin increased markedly and the Ht value showed 78.5%. While the level of consciousness was gradually restored by 600 ml phlebotomy and 1,500 ml saline infusion, dysarthria and hemiplegia became evident. The Ht value early in the morning of the 3rd hospital day was reduced to 59.4%. Although cranial CT and MRI performed 74 days and 15 months, respectively, after the onset of the symptoms failed to reveal any abnormal shadow, he was clinically suspected to have cerebral infarction. These findings emphasize that abrupt increase in Ht or blood viscosity is a possible factor triggering cerebral infarction, and adequate control of Ht value is recommended for the prevention of such a condition in the aged.     

The determination of thymidylate synthetase inhibition for testing fluoropyrimidines--pharmacokinetics and metabolism of carmofur (HCFU) in patients with gynecologic malignancies--Tokai HCFU Study Group for Gynecologic Malignancies

The pharmacokinetics and metabolism of carmofur (HCFU) were studied. Sixty-six patients were administered 100 mg of HCFU orally, and the plasma levels of the HCFU fraction (HCFUf) and 5-fluorouracil (5-FUra) were determined at 0, 1, 2, 4 and 6 hours. The average half-life of HCFUf and 5-FUra were 1.05 and 1.31 hours, and the average areas under the curves (AUC) of the plasma concentration were 6.51 hr X mcg/ml and 0.46 hr X mcg/ml, respectively. Surgical specimens of the tumors were obtained about three hours after the administration and assayed for HCFUf. 5-FUra fluorodeoxyuridine-monophosphate (FdUMP), deoxyuridine-monophosphate (dUMP), total thymidylate synthetase (TS total), and non-FdUMP-bound free enzyme (TS free). The TS inhibition rate (IR) was calculated by the follow method: IR = (TS total-TS free)/TS total X 100 levels of the TS total varied from not-detected (less than 0.10 pmol/g) to 20.5 pmol/g. The average FdUMP: dUMP ratio was 3.44 X 10(3), However, more than 80% inhibitions of TS were observed in nine cases (21.4%). The correlation indicates between TS IR and tissue FdUMP level or FdUMP: dUMP ratio were 0.57 and 0.62 in ovarian malignancies respectively. No significant correlations were observed between TS inhibition and levels of tissue 5-FUra or AUC of 5-FUra.     

Significance of Strain and Sex Differences in the Development of 252Cf Neutron-induced Liver Tumors in Mice

Mouse liver tumors occurring in C3H/HeN, C57BL/6N and C3B6F1 hybrid (C3H × C57BL) were studied following ²⁵²Cf fission neutron irradiation. Three strains of mice of both sexes (about 30 mice/group) were irradiated once with ²⁵²Cf at doses of 0,12.5, 50 and 200 cGy. The groups were observed for 13 months after irradiation. The incidence of liver tumors in the non-irradiated controls was 0% in both sexes of CS7BL/6N, 11.7% in males and 0% in females of C3B6F1 and 39.5% in males and 11.4% in females of C3H/HeN mice. In the four strains of mice thus far studied, including B6C3F1 hybrid (CS7BL × C3H) which was previously studied, ²⁵²Cf irradiation has increased the tumor incidence dose-dependently in males and in females, but less effectively in females. The mean number and size of liver tumors were clearly correlated with tumor incidence. The incidence was always highest in C3H/HeN mice of both sexes, followed by B6C3F1, C3B6F1 and C57BL/6N mice. The influence of sex hormones was studied in B6C3F1 mice of both sexes after 200 cGy of ²⁵²Cf irradiation. In males, the incidence of liver tumors was significantly decreased from 55.2% to 23.3% and 25.9% after orchidectomy, and in females it was slightly decreased from 27.6% to 14.8% and 18.8% after ovariectomy. Supplementation of testosterone in orchidectomized mice did not restore the occurrence of liver tumors.     

Susceptibility of neonatal lipoproteins to oxidative stress

We compared peroxidizability of neonatal and adult lipoproteins exposed to oxidative stress initiated by an azo-compound. Oxygen uptake showed a two-phase pattern, with slow oxygen uptake in the first phase and faster uptake in the second phase. During the first phase, tocopherol was consumed progressively, inhibiting lipid peroxidation by scavenging peroxy radicals. After the tocopherol concentration fell below a critical level, extensive propagation of chain oxidative reactions produced the rapid oxygen uptake in the second phase. In the first phase of neonatal lipoprotein oxidation, a faster oxygen uptake was observed and the length of this phase was shorter than in adults. The oxygen uptake rate in the second phase was smaller in the neonatal lipoproteins. In other words, neonatal lipoproteins were more susceptible to oxidative stress than were adult ones when tocopherol remained in lipoproteins, but after tocopherol depletion the reverse was true. These results were consistent with the finding that in neonatal lipoproteins the tocopherol/lipid ratio was significantly lower (length of the inhibitory phase was closely correlated to the lipoprotein tocopherol content). In addition, the average number of active bisallylic hydrogen atoms, which are considered to determine the relative susceptibility of polyunsaturated fatty acids to oxidation, was significantly smaller (oxygen uptake rate in the second phase was closely correlated to the active bisallylic hydrogen number) in neonatal lipoproteins, and the ratio of active bisallylic hydrogen to tocopherol content (which closely correlated to oxygen uptake rate in the first phase) was also significantly lower compared with the adult ratio. Under physiologic conditions, an intensive oxidation of lipoproteins sufficient to cause lipoprotein tocopherol to fall below critical levels is unlikely to occur.(ABSTRACT TRUNCATED AT 250 WORDS)     

A case of surgical repair in type A aortic dissection with intimal laceration extending into the noncoronary Valsalva sinus

A 50-year old man who had acute type A aortic dissection, underwent prosthetic graft replacement of the ascending aorta. Intimal laceration of the ascending aorta was extending into the noncoronary Valsalva sinus just near the aortic annulus, but the competency of the aortic valve was preserved. Reconstruction of the noncoronary sinus was achieved by approximating intimal edge with Teflon felt reinforced buttress suture, then the ascending aorta was replaced by a Dacron prosthetic graft. His postoperative recovery was uneventful.     

Rat amylin: cloning and tissue-specific expression in pancreatic islets.

Amyloid deposits in the islets of Langerhans of the pancreas are a common finding in non-insulin-dependent diabetes mellitus. The main protein constituent of these deposits is a 37-amino acid peptide known as amylin that resembles calcitonin gene-related peptide, a neuropeptide. We have isolated cDNA clones corresponding to the rat amylin precursor from an islet cDNA library and we show that this peptide is encoded in a 0.9-kilobase mRNA that is translated to yield a 93-amino acid precursor. The amylin peptide is bordered by dibasic residues, suggesting that it is proteolyzed like calcitonin gene-related peptide. The peptide sequences flanking the amylin sequence do not resemble the calcitonin gene-related peptide flanking sequences. RNA hybridization studies show that amylin mRNA is abundant in the islets of Langerhans but is not present in the brain or seven other tissues examined. Dietary changes, such as fasting or fasting and refeeding, have little effect on amylin mRNA expression. This tissue specificity suggests that amylin is involved in specific signaling pathways related to islet function.     

Structural changes and cell viability of cultured epithelium after freezing storage

Numerous clinical reports have shown the utility of cultured epithelial grafting in the field of plastic and reconstructive surgery. Recently, freezing storage of the cultured epithelium has been tried and has successfully grafted after thawing. It is clinically convenient if it is possible for cultured epithelium to keep its normal structure and viability. However, few papers have described the structural changes in cultured epithelium after freezing storage. In the present study, the morphological changes and cell viability of cultured mucosal epithelial sheets after freezing were studied in comparison with cultured epidermal sheets. Furthermore, we discuss the effect of storage temperature and cryoprotectants.As a result, there were some structural changes such as vacuolar degeneration in the cultured mucosal sheets using dimethyl sulphoxide (DMSO) as a cryoprotectant. Such changes were more clearly observed at −80°C than at −196°C with DMSO. However, little morphological change was observed in both epithelial sheets cultured with glycerin. The cell viability analysed by flow cytometry showed that more than 62% of the cells kept their viability after freezing storage. These results suggest that the optimum conditions of freezing for cultured epithelium were −196°C storage by slow cooling methods with glycerin as a cryoprotectant.     

Painless aortic dissection late after aortic valve replacement, presenting as superior vena cava syndrome

A 68-year-old man, who had underwent aortic valve replacement (AVR) with Björk-Shiley disc valve for aortic regurgitation 17 years ago, was transferred to our hospital complaining of facial ruddiness and swelling, without chest or back pain. Preoperative examination revealed DeBakey type II aortic dissection, which caused superior vena cava syndrome (SVC syndrome). Emergent ascending aortic replacement was performed, postoperatively central venous pressure (CVP) decreased from 33 to 9 mmHg, and SVC syndrome was relieved. Painless aortic dissection after AVR, presenting as SVC syndrome, is a rare case, and close follow-up should be performed under consideration of painless aortic dissection late after AVR.     

Familial occurrence of differentiated,nonmedullary thyroid carcinoma

Familial occurrence of differentiated, nonmedullary thyroid carcinoma in 23 patients from 11 families is reported. Five patients were male and 18 were female. The familial relationship of patients was parent and child in 12 cases from 6 families, and siblings in 11 cases from 5 families. Carcinoma of other organs was noted in other members in 8 families. Histological examination revealed 18 papillary, 2 follicular, and 2 anaplastic carcinomas (the 2 anaplastic carcinomas were considered to be transformed from preexisting differentiated carcinoma). In 1 case, the histological type was unknown. The average diameter of the primary lesion was 29.9 mm. Cervical lymph node metastasis was found in 77.8% and local recurrence in 28.6% of the patients. Solid and invasive growth was dominant. On HLA typing, phenotypes of B₇ and DR₁ were significantly redominant in familial patients compared with nonfamilial patients and normal Japanese. Moreover, the haplotype of B₇-C_w7-DR₁ was observed in 5 of 13 patients tested. It is suggested from these observations that some types of differentiated, nonmedullary thyroid carcinoma may show familial occurrence and that they may have common factors with regard to the genetic and immunologic basis of the disease.

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Resumen Se informa la ocurrencia familiar de carcinoma bien diferenciado, no medular, de tiroides en 23 pacientes provenientes de 11 familias, 5 hombres y 18 mujeres. La relación familiar fue padre e hijo en 12 casos de 6 familias, y hermanos en 11 casos de 5 familias. Se observé la presencia de carcinoma de otros órganos en otros miembros de 8 familias. El examen histopatológico reveló 18 carcinomas papilares, 2 foliculares, y 2 anaplásicos (los 2 fueron considerados como transformación de carcinomas diferenciados preexistentes). En un caso no fue conocido el tipo histológico. El diámetro promedio de la lesión primaria fue 29.9 mm. Se hallaron metástasis en ganglios cervicales en 77.8% de los pacientes y recurrencia local en 28.6%. El crecimiento sólido e invasivo apareció como característica dominante. En la tipificación HLA aparecieron como significativamente predominantes los fenotipos de B₇ y DR₁ en pacientes familiares en comparación con pacientes no familiares y japoneses normales. Por otra parte, el halotipo de B₇-C_W7-DR₁ fue observado en 5 de 13 pacientes investigados.Como resultado de estas observationes se sugiere que algunos tipos de carcinomas diferenciados, no medulares, pueden demostrar ocurrencia familiar y que pueden poseer factores comunes relacionados con las bases genéticas e inmunológicas de la enfermedad.

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Résumé On a étudié les caratéristiques du cancer de la thyroïde, dans sa variété différenciée non médullaire, survenu chez 23 patients provenant de 11 familles. Cinq patients étaient des hommes, 18 des femmes. La relation familiale était parent/enfant dans 12 cas provenant de 6 familles, et frère/soeur dans 11 cas provenant de 5 familles. Des membres de 8 autres familles présentaient un cancer d'un autre organe. Il y avait 18 cancers papillaires, 2 cancers folliculaires, et 2 cancers anaplasiques (on a considéré que les 2 cancers anaplasiques étaient des transformations à partir de cancers différenciés préexistants). Dans un cas, le type histologique était inconnu. Le diamètre moyen de la lésion primitive était de 29.9 mm. On a retrouvé des métastases ganglionnaires cervicales chez 77.8% des patients et une récidive locale chez 28.6%. Les tumeurs étaient principalement solides et invasives. Par rapport aux cancéreux non familiaux et à la population japonaise normale, il y avait plus de phénotypes B₇ et DR₁ au système HLA. L'haplotype B₇-C_W7-DR₁ était observé chez 5 des 13 patients testés.On suggère que certains types de cancer différenciés, non médullaires, ayant des facteurs communs génétiques et immunologiques, peuvent survenir dans une même famille.

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Presented at the International Association of Endocrine Surgeons in Sydney, Australia, September, 1987.