Vascularised fibular grafts for reconstruction of extremity bone defects after resection of bone and soft-tissue tumours : a single institutional study of 49 patients.

AIMS: The aims of this study were to analyse the long-term outcome of vascularised fibular graft (VFG) reconstruction after tumour resection and to evaluate the usefulness of the method. PATIENTS AND METHODS: We retrospectively reviewed 49 patients who had undergone resection of a sarcoma and reconstruction using a VFG between 1988 and 2015. Their mean follow-up was 98 months (5 to 317). Reconstruction was with an osteochondral graft (n = 13), intercalary graft (n = 12), inlay graft (n = 4), or resection arthrodesis (n = 20). We analysed the oncological and functional outcome, and the rate of bony union and complications. RESULTS: Five- and ten-year overall survival rates were 89% and 86%, respectively. Local recurrence occurred in two patients. Eight patients developed pulmonary metastases. Bone union was achieved in 44 patients (90%). Fracture occurred in six patients (12%), infection in three (6%), and nonunion in five (10%). The mean Musculoskeletal Tumor Society (MSTS) scores were as follows: osteochondral graft 70%; intercalary graft 73%; inlay graft 89%; and resection arthrodesis 83%. CONCLUSION: Although associated with a relatively high rate of complications, each reconstruction method is useful, with a high rate of successful limb salvage and a good long-term functional outcome. Cite this article: Bone Joint J 2017;99-B:1237-43.

Porphyria cutanea tarda and hepatitis C virus infection.

We studied the prevalence of hepatitis C virus (HCV) infection in 20 Japanese patients with sporadic-type porphyria cutanea tarda (PCT). Seventeen of the 20 patients (85%) had anti-HCV antibodies. Biochemical remission was observed in nine patients, six of whom still had positive HCV RNA copies. These results suggest that HCV infection is a triggering factor for PCT in Japan. However, continuous HCV infection seems to exert little influence on the maintenance of abnormal porphyrin metabolism. Hepatocellular carcinoma (HCC) developed in five of the 17 HCV-positive patients, three of whose PCT was in remission. Four of these patients showed chronic active hepatitis or cirrhosis on liver biopsy. PCT patients with HCV infection should be followed up long-term because of the possibility of HCC. To evaluate the risk of HCC, liver biopsy may be required, even when the patient is in biochemical remission.

Relationship between N-acetyltransferase (NAT) activity and liver protoporphyrin level in experimental porphyria.

The results of our previous studies demonstrated that isonicotinic acid hydrazide (INH) can aggravate griseofulvin (GF)-induced protoporphyria in mice. To elucidate this phenomenon, we studied the relationship between liver protoporphyrin (PP) levels and N-acetyltransferase (NAT) activity, which is known to be a major catabolic enzyme of INH metabolism in the liver. The results revealed a significant correlation between liver PP levels and NAT activity in the mice fed 0.1% GF and 0.05% INH. In this group, mice with high NAT activity developed severe protoporphyria. There was no correlation, however, between liver PP levels and NAT activity in the mice fed GF alone or INH alone. The result suggested that INH metabolites formed by NAT enhance the hepatotoxicity of GF in mice.

Quantitative analysis of ferrochelatase mRNA in blood cells of erythropoietic protoporphyria patients.

Ferrochelatase (FC; heme synthetase, EC 4.99.1.1.) catalyses the synthesis of heme from protoporphyrin IX, the final step in the heme synthetic pathway. The hereditary deficiency of this enzyme gives rise to erythropoietic protoporphyria (EPP). We developed a rapid, non-radioactive means of measuring human FC mRNA levels in the EPP patients. It is based on the reverse transcriptase-polymerase chain reaction (RT-PCR) performed on the RNA obtained from peripheral blood. The amplified DNA was detected by agarose gel electrophoresis with ethidium bromide staining and the fluorescent intensity was measured by scanning densitometry applied directly to Polaroid 665 negative film. The relative expression level of FC mRNA, compared with that of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) mRNA, was estimated at several points in the exponential phase of PCR cycles or at a point in the exponential phase of PCR performed on serially diluted the cDNA samples. The estimate of the FC mRNA by this method correlated well with the level of the FC mRNA measured by Northern blotting in the EB virus-transformed lymphocytes of the same patients. The level of the FC mRNA appeared to vary among the patients in whom a decreased level of enzymatic activity was indicated.

[Experimental porphyria].

There are many chemicals that affect porphyrin metabolism. Certain of these can be used to induce experimental porphyria in animal. Human porphyrias are relatively uncommon, thus preventing their adequate examination in human patients. But using experimental animals, the pathogenesis, biochemical pathways and treatment of these diseases may be studied. In this paper, we conducted our own investigations on griseofulvin induced protoporphyria, and also reviewed experimental porphyrias induced by hexachlorobenzen and polychlorinated biphenyls.

[Polychlorinated biphenyls (PCBs) and polychlorinated quaterphenyls (PCQs) concentrations in skin surface lipids and blood of patients with Yusho].

The relationship between Polychlorinated Biphenyls (PCBs), and Polychlorinated Quaterphenyls (PCQs) concentrations in the skin surface lipids and blood was investigated in twenty two patients with PCB poisoning (Yusho) and 9 control subjects were analyzed. The collection of skin surface lipids was performed by the method of cotton pad with 70% ethyl alcohol. The alkaline decomposition method described as "the official standard analytical methods for the isolation of PCBs and PCQs fractions" was used. In the blood of control group, the mean value of PCBs concentration was 1.8 ng/g, and that of PCQs concentration was very low and undetectable by our analytical method. On the other hand, the PCBs concentration in the Yusho group was three times higher than those in the control group. The mean value of PCQs concentration was 1.90 ng/g in Yusho group, while it was not detectable in the control group. In the skin surface lipids of patients with Yusho, the mean value of PCBs concentration was 668.6 ng/g, but was 256.7 ng/g in the control group. The mean value of PCQs concentration in the skin surface lipids of Yusho patients was 35.4 ng/g, although it was not detected in the control group. These values of the skin surface lipids in 1993 were decreased as compared with those in 1992. PCBs and PCQs levels in the skin surface lipids were higher than those in the blood. These findings suggests that cutaneous sebaceous system is one of the excretory systems of polyhalogenated chemicals, such as PCBs or PCQs, when these chemicals are precipitated in human or mammalian.

[Effects of polychlorinated biphenyls (PCBs) on porphyrin metabolism--experimental porphyria induced by large single doses of PCBs].

The effects of large single doses of PCBs and iron overload on porphyrin metabolism were investigated in male C57BL/6 mice. A single intraperitoneal dose of Kanechlor-500 (10 mg/mouse) caused urinary uroporphyrin to increase three days after injection. This increase was transient without porphyrin accumulation in the liver. Iron overload (12.5 mg/mouse) showed a tendency to prolong the action of PCBs.

Relationship between porphyria cutanea tarda (PCT) and viral hepatitis.

Recent reports have revealed the high prevalence of serological markers of viral hepatitis in porphyria cutanea tarda (PCT). We present two cases of PCT associated with hepatitis C and discuss the relationship between PCT and viral hepatitis. Case 1: A 50-year-old Japanese male noticed blisters, erosions, and fragility on sun-exposed areas of his skin in November of 1990. He had no history of excessive alcohol intake. He had been taking analgesics for eighteen years. Case 2: A 64-year-old Japanese male was referred in October of 1989 because of pigmentation on sun-exposed areas of his skin. He had been drinking alcohol excessively for 43 years. The hepatitis C virus (HCV) antibody was present in each case. Tests for the HCV antibody and hepatitis B serological markers were run in 5 other patients. HCV antibody was present in 3 of them. The two cases negative for the HCV antibody exhibited the hepatitis B antibody. We speculated that viral hepatitis infection may play an important role in precipitating PCT in cases with a history of a long term excessive intake of alcohol or chemicals.

[The influence of ursodesoxycholic acid (URSO) on griseofulvin (GF)-induced protoporphyria].

To investigate the influence of ursodesoxycholic acid (URSO) on griseofulvin (GF)-induced protoporphyria mice, analysis of hepatic, erythrocytic, and fecal porphyrin levels and histopathological examinations were performed in dd-Y strain mice treated with 0.5% GF and/or 0.5% URSO. We observed no difference of hepatic and fecal porphyrin levels between the GF group and GF with URSO group, although an elevation of erythrocytic porphyrin levels was seen in the GF with URSO group. However, remarkable hepatic atrophy revealed in the GF with URSO group. Furthermore, a strong emission of red fluorescence was observed in the liver under long wave ultraviolet. Histopathologically, many focal necrosis was found in the liver specimen treated with GF and URSO. We expected that URSO might facilitate the excretion of porphyrin from bile to feces because of suppression of transfer from serum to erythrocyte like cholic acid (CA). But, the action of URSO appears to be different from that of CA. We consider that the 0.5% concentration of URSO plays a role in the cytotoxic effect to the liver.

The synergistic effect of chlorinated chemicals (trichlorosalicylanilid, 4-chloro-m-cresol, trichlorophenoxyacetic acid, trichloroethanol, trichloromethiazide, trichlorofon and trichloroacetaldehyde) and low concentrations of griseofulvin on porphyrin metabolism.

The synergistic effect of chlorinated chemicals and 0.1% griseofulvin (GF) on porphyrin metabolism was investigated. Drinking water containing 0.03% trichlorosalicylanilid, 0.1% 4-chloro-m-cresol, 0.1% trichlorophenoxyacetic acid, 0.3% trichloroethanol, 0.1% trichloromethiazide, 0.3% trichlorofon and 0.1% trichloroacetaldehyde was given separately to dd-y strain mice. Each group was divided into two subgroups, one treated with feed containing 0.1% GF and the other treated with normal feed. The treatments were continued for 45 to 165 days, after which porphyrins in the erythrocytes, feces and liver were analyzed by a chromatographic method. In the 0.03% trichlorosalicylanilid and 0.1% GF group, 0.1% 4-chloro-m-cresol and 0.1% GF group, 0.1% trichlorophenoxyacetic acid and 0.1% GF group and 0.3% trichloroethanol and 0.1% GF group, a slight elevation of fecal coproporphyrin and protoporphyrin was seen. There was no elevation of hepatic and erythrocytic porphyrins. This result shows that the chemicals used in this study did not have a potential for porphyria, but that they are capable of inducing slight porphyrin abnormalities in a synergistic reaction with 0.1% GF.

A comparative study on the concentrations of polychlorinated biphenyls (PCBs) and polychlorinated quaterphenyls (PCQs) in the blood and hair of "Yusho" patients and inhabitants of Nagasaki Prefecture.

The relationship between polychlorinated biphenyl (PCB) and polychlorinated quaterphenyl (PCQ) concentrations in the blood and hair was investigated. The materials in this study consisted of 49 blood samples and hair obtained from 27 patients with PCB poisoning (Yusho) and 22 normal controls. The alkaline decomposition method described in the official standard analytical methods for the isolation of PCB and PCQ fractions was used. In the blood of the control group, the mean concentration of PCBs was 2.25 ppb, while the concentration of PCQs was too low to be detected by our analytical method. On the other hand, the mean concentration of PCBs in the Yusho group was about 2.8 times higher than that in the control group. The mean concentration of PCQs in the blood was 0.61 ppb in the Yusho group, but PCQs were not detectable in the control group. In the hair, the mean concentration of PCBs was 25.85 ppb and 9.41 ppb in the Yusho group and control group respectively. The mean concentration of PCQs in the hair of Yusho patients was 0.44 ppb, but PCQs were not detected in the control group. The PCB level in the hair was higher than that in the blood, but the PCQ level in the hair was lower than that in the blood. These results suggest a difference of excretory system among polyhalogenated compounds such as PCBs or PCQs. We consider that PCBs display a greater affinity than PCQs for the pilosebaceous system of the human skin.(ABSTRACT TRUNCATED AT 250 WORDS)

A comparative study on polychlorinated biphenyls (PCB) and polychlorinated quaterphenyls (PCQ) concentrations in subcutaneous fat tissue, blood and hair of patients with yusho and normal control in Nagasaki prefecture.

The relationship between PCB and PCQ concentrations in the blood, subcutaneous fat tissue and hair was investigated in this study. PCB and PCQ concentrations in twenty four patients with PCB poisoning (yusho) and 59 normal controls were analyzed. The alkaline decomposition method described in the official standard analytical methods for the isolation of PCB and PCQ fractions was used. The mean value of PCB concentrations was 2.43 ppb, CB% ratio was 0.69 and the PCQ concentration in the blood of the control group was too low to be detected by our analysis. On the other hand, the PCB concentration and CB% ratio in the yusho group were two times higher than those in the control group. The mean value of PCQ concentration was 1.34 ppb in the yusho group although it was below the level of detection in the control group. The mean PCB concentration in the hair of patients with yusho was 28.92 ppb, and 8.06 ppb in the control group. CB% ratio in the hair of patients with yusho was two times higher than that in the control group. The mean value of PCQ concentration in the hair of patients with yusho was 0.55 ppb although it was not detected in the control group. The PCB and PCQ concentrations in the hair were not greatly elevated when compared with those in the subcutaneous fat tissue. However, the hair is an excellent sample for the detection of these chemicals because it can be collected simply without operation.

Regional differences of PCB and PCQ concentrations in the blood and subcutaneous fat tissue of residents of Nagasaki.

In this study, we analyzed PCB and PCQ concentrations in the subcutaneous fat tissue of residents of Nagasaki Prefecture, and compared these levels between the blood and subcutaneous fat tissue of people living in various parts of the prefecture. Seventy-one inhabitants were examined. In the blood, PCB concentrations in Tamanoura and Fukue were significantly higher than those in Nagasaki City. The CB% ratio in Tamanoura was significantly higher than that in Nagasaki and Isahaya. PCQ concentrations were below detection level except in one case. PCB concentrations in fishery areas showed higher levels than urban or agricultural areas. PCB concentration in the subcutaneous fat tissue was 100 times higher than that in the blood. PCQs could be detected in almost all of the subcutaneous tissues, but there was no regional difference in the PCQ concentration.

The effect of chlorinated chemicals on porphyrin metabolism--the synergistic effect with chlorinated chemicals and low concentrations of griseofulvin.

The synergistic effect of chlorinated chemicals and 0.1% griseofulvin on porphyrin metabolism was investigated. Feeds containing 0.1% 4-chloro-m-cresol, 0.1% cumarone or 0.25% trichloroacetic acid with or without 0.1% griseofulvin were given to dd-y strain mice respectively. The treatments were continued for 10 to 450 days, after which coproporphyrin and protoporphyrin in the erythrocytes and liver were analyzed. In the 0.1% griseofulvin alone group, protoporphyria was induced in 6 of 55 dd-y strain mice, although the other 49 mice did not show any abnormal porphyrin metabolism and the severity of the protoporphyria was mild in the 6 mice. In the 4-chloro-m-cresol group, a slight elevation of erythrocytic porphyrins was seen, but the difference was not statistically significant. Elevation of the hepatic porphyrins was not seen. Trichloroacetic acid and cumarone did not influence porphyrin metabolism, and also there was no synergistic effect of griseofulvin on porphyrinopathy. These results suggest that the three chemicals selected in this study are not capable of inducing porphyrinopathy.