Radiotherapy with 8 MHz radiofrequency-capacitive regional hyperthermia for pain relief of unresectable and recurrent colorectal cancer.

PURPOSE: The purpose of this study was to assess the pain relief in patients with unresectable and recurrent colorectal cancer treated with radiation plus 8 MHz radiofrequency-capacitive regional hyperthermia and to identify predictors of the good outcome. METHODS: Between February 1986-May 2003, 41 patients with primarily unresectable and recurrent colorectal cancer that caused pain were treated with thermoradiotherapy at the hospital and retrospectively analysed. Radiotherapy was administered with a mean total radiation dose of 56 Gy. Hyperthermia was usually applied within 30 min after radiotherapy once or twice a week. For cooling of the skin surface, the overlay boluses were applied in addition to regular boluses. The external cooling unit has been used to reinforce the cooling ability of the overlay bolus and achieve strong surface cooling to reduce the preferential heating of the subcutaneous fat tissue and treat with more RF-output in 17 patients since January 1997. RESULTS: Pain relief was obtained in 83% of the patients. Multi-variate analysis by logistic regression to evaluate the effects of certain factors on pain relief (complete response + good response) was strongly correlated with the presence of radiating pain to leg(s) (p < 0.05). The median follow-up was 18 months. The median duration of pain relief was 7.0 months. For the 27 patients in whom the tumour temperature was estimated, the median duration of pain relief was 14.6 months for the patients with a mean average tumour temperature of > 42.5 degrees C and 5.7 months for those of < 42.5 degrees C (p < 0.05). In the 18 patients with radiating pain to leg(s), use of strong superficial cooling and the higher numbers of hyperthermia treatments were better prognostic factors for the duration of pain relief (p < 0.01 and p < 0.05, respectively). CONCLUSIONS: Radiotherapy with 8 MHz radiofrequency-capacitive regional hyperthermia provided an efficient, effective means on pain relief of treating unresectable and recurrent colorectal cancer. The duration of pain relief can be prolonged, if an adequate heating is achieved, especially in the patients with radiating pain to the leg(s).

Effect of 8-MHz radiofrequency-capacitive regional hyperthermia with strong superficial cooling for unresectable or recurrent colorectal cancer.

A well-known disadvantage of a radiofrequency-capacitive device for deep-seated tumours is preferential heating of the subcutaneous fat tissue. The authors previously developed the hyperthermia with their own external cooling unit and achieved strong superficial cooling, and reported its usefulness for the reduction of the preferential heating. The purpose of the present study was to evaluate the effect of hyperthermia with strong superficial cooling on the treatment results for unresectable or recurrent colorectal cancers. From 1986 to 2002, 44 patients with primary unresectable or locally recurrent colorectal cancer treated with thermoradiotherapy were analysed retrospectively. The patients with obesity as a subcutaneous fat thickness more than 3 cm, a high age or other serious complications did not undergo therapy. The results were compared between 17 cases with strong superficial cooling treated after 1997 (Group A) and 27 cases without strong superficial cooling treated before 1996 (Group B). Significant differences in thermometry data of T(max), T(ave) and T(min) were noted between Groups A (45.3, 44.4 and 43.6 degrees C, respectively) and B (42.9, 42.0 and 41.1 degrees C, respectively) (p<0.01). Complete response plus partial response rates were better for Group A than for Group B (59 versus 26%, p = 0.05). Multivariate analysis by logistic regression to evaluate the effects of certain factors on complete response plus partial response was strongly correlated with strong superficial cooling (p<0.05). The median survival times for overall survival were 24.3 months for Group A and 17.1 months for Group B (p<0.05). Eight-megahertz radiofrequency-capacitive regional hyperthermia with strong superficial cooling is potentially useful for improving treatment results in unresectable or recurrent colorectal cancers.

Threshold effect for teratogenic risk of radiation depends on dose-rate and p53-dependent apoptosis.

PURPOSE: To obtain evidence that the p53 gene is indispensable for reduction of high teratogenic risk of radiation at a high dose-rate to zero risk by lowering the dose-rate. MATERIALS AND METHODS: Wild-type p53(+/+), heterozygous p53(+/-) and null p53(-/-) mice were exposed to gamma-rays at high or low dose-rates during days 9.5-10.5 of gestation. The incidence of malformations and prenatal deaths was studied. Frequencies of cells dying by apoptosis were measured during or after protracted irradiation. RESULTS: After irradiation with 2 Gy, the frequency of apoptotic cells increased to 20% for p53(+/+) mice and did not increase at all for p53(-/-) mice. For p53(+/+) mice, 2 Gy y-rays induced 70% malformations when given at 1.06 Gy/min, but no malformations above the control when given at 1.2 mGy/min. In contrast, after irradiation of p53(-/-) foetuses with 2 Gy at 1.2mGy/min, the incidence of malformations increased 12% above control levels. CONCLUSION: Foetal irradiation with 2 Gy at 1.2 mGy/min was not teratogenic for p53(+/+) mice but teratogenic for p53(-/-) mice. This indicates that the p53 gene is indispensable for a threshold effect in the risk of radiation at low doses or dose-rates.

Preparation and properties of novel gramicidin S analogs possessing a tri-, tetra- or pentamethylene bridge between ornithine side chains.

Gramicidin S (GS) analogs in which the Ndelta atoms of the two Orn side chains are linked by an oligomethylene bridge [-(CH2)n-; n=3-5] were prepared via the bis(p-nitrobenzenesulfonyl) derivative [Orn(NBS)2,2']GS. For comparison the nonbridged secondary amino group-containing analog [Orn(Me)2,2']GS was also prepared. 1H NMR and CD spectral analysis indicated that these analogs adopt the same beta-sheet conformation as GS. The antimicrobial activities of these analogs were very similar, but were slightly dependent on the bridge chain length, the trimethylene-bridged analog being the most potent.

[Current status of the conservative treatment of urinary bladder for invasive bladder cancer].

During the 3 years from 1987 to 1990, we gave hyperthermia to 11 of the patients who visited our department for the treatment of invasive bladder cancer. Results and prognosis are reported. Stage and grade of the cancer before the treatment in 11 cases were T2 in 5 cases, T3 in 3 cases, T4 in 3 cases, transitional cell carcinoma (TCC) grade 2 in 8 cases, TCC grade 3 in 2 cases, and TCC grade 3 + anaplastic carcinoma in 1 case. Complications were observed in 8 of the 11 cases, such as severe heart disease and others. Pretreatment of radiation therapy, transurethral resection or chemotherapy was given in all cases. Hyperthermia was performed combined with hydroxypropyl cellulose-(HPC)-adriamycin, or radiation therapy, and the following results were obtained: complete response (CR) in 4 cases, partial response (PR) in 4 cases, no change (NC) in 2 cases and progressive disease (PD) in 1 case. Among 4 cases of PR, total cystectomy was performed in 3 cases. These 3 cases and the 4 cases of CR are alive now, but the other 4 patients died.

The genetic and biochemical basis of polyketide metabolism in microorganisms and its role in drug discovery and development.

The possibilities for the design of new drug screening and development strategies directed to a specific objective on the basis of genetic engineering of microorganisms is discussed from two points of view. Firstly, results of work on genetic hybrids of STREPTOMYCES species for the production of new metabolites such as mederrhodin (1) and aloespanoarin II (4) are described. Secondly, the enhanced production of known metabolites such as tetracenomycin A (2) (11) and tetracenomycin C (9) by recombinant STREPTOMYCES species is considered. Mechanistic aspects of polyketide metabolism are included.

The genetic and biochemical basis of polyketide metabolism in microorganisms and its role in drug discovery and development.

The possibilities for the design of new drug screening and development strategies directed to a specific objective on the basis of genetic engineering of microorganisms is discussed from two points of view. Firstly, results of work on genetic hybrids of Streptomyces species for the production of new metabolites such as mederrhodin (1) and aloespanoarin II (4) are described. Secondly, the enhanced production of known metabolites such as tetracenomycin A2 (11) and tetracenomycin C (9) by recombinant Streptomyces species is considered. Mechanistic aspects of polyketide metabolism are included.

Inhibition of mutagenicity by glycyrrhiza extract and glycyrrhizin.

The effects of Glycyrrhiza extract and one of its components, glycyrrhizin, on the mutagenicities of several mutagens were investigated by means of a modification of the Ames' test. Both inhibited the mutagenicities of 3-amino-1,4-dimethyl-5 H-pyrido[4,3-b]-indole (Trp-P-1) and 3-amino-1-methyl-5 H-pyrido[4,3-b]indole. Since the Glycyrrhiza extract and glycyrrhizin inhibited the mutagenicity of activated Trp-P-1, it was clear that their inhibitory effects were not due to inhibition of the enzyme activity of the S9 fraction. Both Glycyrrhiza extract and glycyrrhizin also inhibited the mutagenicities of benzo[a]pyrene, 3-methylcholanthrene, 2-naphthylamine, 2-amino-6-methyldipyrido[1,2-a:3',2'-d]-imidazole, dimethylnitrosoamine and dimethylaminoazobenzene. The mutagenicity of 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide (AF-2) was inhibited by the Glycyrrhiza extract but not by glycyrrhizin. This suggested that a component different from glycyrrhizin, present in the Glycyrrhiza extract, inhibited the mutagenicity of AF-2.

[An experiment of acute fulminant severe ulcerative colitis in a 75- year-old male--a case report and a consideration of the surgical treatment of elderly patients with severe ulcerative colitis].

This is a case report of 75 year-old male patient with acute fulminant severe ulcerative colitis who underwent proctocolectomy after emergency ileostomy and decompression colostomy, and consideration of surgical treatment for elderly patients with severe ulcerative colitis are also discussed. A 75 year-old male was hospitalized as emergency case with complaints of high fever, severe abdominal pain and diarrhea. He was diagnosed as acute fulminant ulcerative total colitis by colonoscopy and barium enema examination. He had urgent operation of ileostomy and decompression cecostomy in the presence of severe disease after intensive medical treatment had failed. After a few days toxic signs gradually disappeared and general status was slightly improved. And then, radical operation of proctocolectomy and permanent ileostomy was successfully performed 3 weeks after the previous operation. We wish to emphasize in the elderly patients, namely 60 years and over with severe ulcerative colitis, that radical surgical treatment such as proctocolectomy or total colectomy should be performed after minimal laparotomy with decompression colostomy and ileostomy, because they do not survive so readily as the younger patients.

Swine fever. Immunisation of piglets.

Vaccination against Swine Fever using the CL Chinese strain can be done in 7-day-old piglets if they are born of non-immune sows. The simultaneous weaning and vaccination emphasises the safety of this strain. The excellent immunity observed confirms the immunocompetence of 7-day-old piglets. In piglets born of immune sows and also weaned at 7 days, passive protection can extend beyond the age of 2 months if the sow is vaccinated several months prior to gestation. The immune level of the piglets would seem to depend on the interval between vaccination of the sow and farrowing and can be attributed to the quality of the antibodies transmitted by the colostrum. Piglets born of sows vaccinated 10 months prior to farrowing can be vaccinated as early as 5 weeks; the protection percentage observed at the age of about 6 months is over 80%. A booster injection at this age then confers immunity to future breeders throughout their economic life, i.e. 4 years in the reported experiment.

[Hog cholera: active immunity conferred by the Chinese strain vaccine to young pigs born to immune sows]. / Peste porcine classique. immunisation active conferee par la souche chinoise CL aux porcelets issus de truies immunes.

This paper deals with the comparative development of active immunity in young pigs which were born from unvaccinated sows and from recently vaccinated sows. The development of immunity is expressed by the neutralizing serum antibody titer and protection against a pathogenic virus. The results show that: --the post-vaccinal increase in antibodies is inversely proportional to the titer of passive antibodies at the time of vaccination, --protection at the end of economic life depends on the antibody titer at the time of the challenge, --young pigs born from a mother which is not immune can be vaccinated starting at the age of 7 days, --the percentage of protection at the end of economic life of vaccinated baby pigs with colostral antibodies ranges from 50% when the vaccination was carried out at the age of 7 days to 100% when the vaccination occurs at the age of 2 months.