Superior mesenteric artery syndrome with vascular calcification in a maintenance hemodialysis patient.

INTRODUCTION: Superior mesenteric artery (SMA) syndrome is defined as trapping of the third portion of the duodenum between the SMA and the aorta. In this case, vascular calcification associated with dialysis might have contributed to the onset of SMA syndrome. CASE: The patient was a 74-year-old woman who had been receiving maintenance hemodialysis. She developed sudden onset of severe recurrent vomiting during admission for pseudo-gout. CT of the abdomen revealed duodenal obstruction with an abrupt cutoff in the third portion of the duodenum, and dilatation of the first and second portions of the duodenum. The aortomesenteric angle was significantly sharp. In addition, severe vascular calcification was revealed in the SMA and aorta. The initial treatment was decompression of the obstruction by a nasogastric tube and parenteral nutrition for the management of fluid and electrolyte imbalance. She recovered with only conservative treatment. CONCLUSION: Vascular calcification of the SMA and aorta might have contributed to compression of the third portion of the duodenum. Vascular calcification associated with dialysis could be a factor in SMA syndrome.

Synthesis and antibacterial activity of 2,2'-dithiobis(benzamide) derivatives against Mycobacterium species.

A series of compounds, which are analogues of 2,2'-dithiobis(benzamide), were synthesized and tested for in vitro antibacterial activity against Mycobacterium tuberculosis H37Rv including resistant strains against streptomycin, kanamycin, or isonicotinic acid hydrazide. MICs of these compounds against atypical mycobacteria, Mycobacterium kansasii and Mycobacterium intracellulare were also examined. Structure-activity relationships were found in a series of (acyloxy)alkyl ester derivatives depending upon the length of alkyl carbon chain. The MIC of the most potent compound, 2,2'-dithiobis[N-[3-(decanoyloxy)propyl]benzamide] [56] was superior or at least equivalent to streptomycin, kanamycin, and ethanbutol. All the compounds showed no cross-resistance between the current antitubercular agents.

Synergistic effects of phenobarbital and thiourea on proliferative lesions in the rat liver.

To evaluate the effects of phenobarbital (PB) and thiourea (TU), alone or in combination, on proliferative lesions of the liver, thyroid and lung, male F344 rats initiated with 2000 mg/kg body weight N-bis(2-hydroxypropyl) nitrosamine (DHPN) were given diet and/or drinking water containing 0% PB/TU (group 1), 1000 ppm PB (group 2), 0.1% TU (group 3) and 500 ppm PB and 0.05% TU (group 4), from weeks 2 to 20 for 19 weeks. Group 4 showed remarkable increases in the number of hepatocellular altered foci per animal, the values being superior to the averages of groups 2 and 3. The number of thyroid proliferative lesions per animal was highest in group 3 and lowest in group 2. Lung proliferative lesions were induced in all groups, but no modifying influence on their development was evident in the combined group. The present results indicate that combined administration of PB and TU exerts synergistic enhancing effects on hepatocarcinogenesis.

Effect of thyroid stimulating hormone on the development and progression of rat thyroid follicular cell tumors.

Time course changes in cell proliferative activity of thyroid focal hyperplastic and tumorous lesions as well as blood thyroid-related hormones in male F344 rats initiated with N-bis(2-hydroxypropyl)nitrosamine (DHPN: 2800 mg/kg body weight, single s.c. injection) were examined following chronic administration of 0.1% sulfadimethoxine (SM) in the drinking water for 1, 4, 8, 12 and 16 weeks and at the end of a subsequent 4-week recovery period. Serum thyroid stimulating hormone (TSH) levels increased rapidly from week 1 of SM treatment, reaching a peak at week 8, and then decreased gradually with prolongation of treatment period, although remaining significantly elevated as compared with the corresponding controls at all time points up to week 16. Follicular cell hyperplasias and adenomas of the thyroid occurred from week 4 and carcinomas from week 8. All of these lesions showed high cell proliferative activities corresponding to high serum TSH levels during the early stage, but the levels in hyperplasias and adenomas decreased rapidly with prolongation of SM treatment. After the recovery period, serum TSH levels had returned to below the normal range and cell proliferation in follicular hyperplasias and adenomas had stopped or was very low. Some carcinomas demonstrating invasive growth also showed remarkable decreases in the cell proliferative activity. The results of our study strongly suggest that a high serum TSH level plays an important role in the early stage of thyroid tumorigenesis and that some tumors exhibiting invasive growth are still dependent on TSH stimulation.

Effect of CABG on coronary flow reserve in atresia of the left coronary ostium.

We evaluated the change of coronary flow reserve using a Doppler guidewire before and after coronary artery bypass grafting to assess the coronary hemodynamic effect of surgical revascularization in a 13-year-old boy with congenital atresia of the left coronary ostium, which is one of the rarest of the congenital coronary anomalies. Coronary flow reserve in the right coronary artery and left anterior descending artery increased significantly after coronary revascularization, and a microvascular bed developed in the left anterior descending artery.

Studies on the carcinogenicity of potassium iodide in F344 rats.

A chronic toxicity and carcinogenicity study, in which male and female F344/DuCrj rats were given potassium iodide (KI) in the drinking water at concentrations of 0, 10, 100 or 1000 ppm for 104 weeks, and a two-stage carcinogenicity study of application at 0 or 1000 ppm for 83 weeks following a single injection of N-bis(2-hydroxypropyl)nitrosamine (DHPN), were conducted. In the former, squamous cell carcinomas were induced in the salivary glands of the 1000 ppm group, but no tumors were observed in the thyroid. In the two-stage carcinogenicity study, thyroidal weights and the incidence of thyroid tumors derived from the follicular epithelium were significantly increased in the DHPN+KI as compared with the DHPN alone group. The results of our studies suggest that excess KI has a thyroid tumor-promoting effect, but KI per se does not induce thyroid tumors in rats. In the salivary gland, KI was suggested to have carcinogenic potential via an epigenetic mechanism, only active at a high dose.

Study on the carcinogenicity of tannic acid in F344 rats.

The carcinogenicity of tannic acid, a compound that is used as a food additive, a clarifying agent and a refining agent, was examined in F344 rats of both sexes. Tannic acid was dissolved in distilled water at concentrations of 0.25 and 0.5%. The doses were selected on the basis of results from a 13-wk subchronic study. Groups of 50 male and 50 female rats were given one of these solutions ad lib. as their drinking water for up to 2 yr. The mean body weights of the treated males were essentially comparable with those of the controls, whereas treated females had lower mean body weights than the control group. A variety of tumours developed in all groups, including the control group, but all the neoplasms were histologically similar to those known to occur spontaneously in this strain of rats, and no statistically significant increase in the incidence of any tumour was found in the treated groups of either sex. Thus, it is concluded that, under the conditions of the experiment, tannic acid has neither carcinogenic potential in F344 rats nor modifying effects on spontaneous tumour development.

Lack of carcinogenicity of cyanoguanidine in F344 rats.

The carcinogenicity of cyanoguanidine, a compound used in the production of melamine, guanidine salts and guanamine derivatives, was examined in male and female Fischer 344 rats fed CRF-1 pulverized diets containing 0, 2.5 and 5% cyanoguanidine for up to 2 yr. The rats were randomly allocated to three groups, each consisting of 50 males and 50 females. The mean body weight gains in both sexes of the 5% group and in females of the 2.5% group were significantly lower than the control values after wk 1 of treatment. No other signs of toxicity were seen in any of the rats throughout the treatment period. Histopathologically, various tumours developed in all groups, including the control group, but these were all similar to those known to occur spontaneously in this strain of rats, and no toxicologically significant increase was found for any lesion type in the treated groups. On the basis of these results, it is concluded that cyanoguanidine exerts no carcinogenic potential in F344 rats when administered for up to 2 yr under the conditions of the present study.

The mode of action of nanaomycin A in Gram-positive bacteria.

The mode of action of nanaomycin A on Gram-positive such as Staphylococcus aureaus, Bacillus cereus and Streptococcus faecalis was investigated. Nanaomycin A inhibited the biosyntheses of protein, DNA, RNA and cell-well peptidoglycan to a similar extent. It increased the oxygenous respiration of S. aureus cells at the minimal inhibitory concentration. The cells preincubated with nanaomycin A showed stimulation of proton influx after addition of N,N'-dicyclo-hexylcazrbodiimide, an inhibitor of Ca++, Mg++-ATPase. Nanaomycin A seems to interfere with the cytoplasmic or to inhibit coupling of oxidative phosphorylation, followed by secondary inhibitory effect on protein, nucleic acids and cell-wall peptidoglycan biosyntheses.

Synergistic activity of astromicin and beta-lactam antibiotics against Pseudomonas aeruginosa in vitro and in vivo.

Synergistic activity of astromicin and an antipseudomonal beta-lactam antibiotic such as piperacillin, cefsulodin or carbenicillin against Pseudomonas aeruginosa was demonstrated in vitro and in vivo. Synergy in vitro was observed more often when astromicin was combined with piperacillin or cefsulodin than when it was combined with carbenicillin. The combination of astromicin with piperacillin showed a bactericidal activity against Pseudomonas aeruginosa at a bacteriostatic concentration of each antibiotic alone. The synergy observed in vitro was reproduced against experimental mouse infections, and the astromicin-piperacillin or cefsulodin combination produced significantly greater protective effects than the single use of individual antibiotics.

Chemical modification of fortimicins. III. preparation of N-substituted fortimicin A derivatives.

The 1, 2' or 6'-amino group of fortimicin A was alkylated or acylated and the antimicrobial activities of the derivatives were compared with each other. 2'-N-Substituted fortimicins A were active against the fortimicin A resistant strain which produced AAC(3)-I. AAC(3)-I is the only enzyme which can inactivate fortimicin A. Among the derivatives prepared in the present study, 2'-N-[(S)-4-amino-2-hydroxybutyl]fortimicin A showed stronger activity than fortimicin A.

Collaborative work to evaluate toxicity on male reproductive organs by repeated dose studies in rats 13). Effects of a single oral dose of cyclophosphamide.

As part of a collaborative effort to evaluate whether effects on male reproductive organs of chemicals can be detected within two-week in toxicity studies, eight-week-old male Sprague-Dawley rats were given a single oral administration of 100 mg/kg of Cyclophosphamide (Cp), and sacrificed at 1, 3, 7 and 14 days thereafter. The numbers of seminiferous epithelial cells were counted in the seminiferous tubules of stages II-III, V, VII and XII of the spermatogenic cycle. Animals showed decreased spermatogonia at Day 3, decreased spermatogonia and preleptotene spermatocytes at Day 7, and decreased spermatogonia and zygotene spermatocytes at Day 14. We also detected decrease of zygotene spermatocytes on careful routine/traditional histopathological examination at Day 14. These results suggest that the testicular toxicity of Cp can be detected within two weeks after treatment with a sufficient dose in rats.

Thyroid proliferative lesions induced by anti-thyroid drugs in rats are not always accompanied by sustained increases in serum TSH.

To examine changes in serum TSH and determine whether the sustained excess is necessary for the development and/or progression of thyroid tumors, male F344 rats were administered drinking water containing thiourea (TU), at 0.1 or 0.05%, or sulfadimethoxine (SM), at 0.025 or 0.0125%, for one week in Experiment I. All of the treated animals showed decreased serum levels of T3 and T4 and an increased TSH. In Experiment II, male rats were given a s.c. injection of N-bis(2-hydroxypropyl) nitrosamine (DHPN:1500 mg/kg BW) and, starting one week later, received drinking water containing the same doses of TU or SM as in Experiment I for the following 20 weeks. Thyroid follicular proliferative lesions were induced in most rats treated with TU and SM. However, these treated animals did not demonstrate any consistent alterations in serum T3, T4 and TSH levels, except for the high dose TU group. The present studies thus suggest that thyroid tumors can grow even under conditions of fluctuating serum TSH levels during the progression phase, although TSH stimulation might be an absolute requirement in the early phase of tumor development.

[Agar tube method for the bioassay of antibiotics (author's transl)].

A simplified bioassay system for antibiotics has been presented. Glass tubes with open ends and pits are filled with agar medium containing test microbes by immersing vertically into the agar medium while it is warm. These agar tubes are inserted in test solutions and incubated. The growth-inhibitory zones appear in respective tubes due to upward diffusion of the antibiotic. The heights of such zones from the bottom of agar tubes are measured.

[The therapeutic effect of nanaomycin A against experimental Trichophyton mentagrophytes infection in guinea pigs (author's transl)].

Acute toxicity of nanaomycin A was tested in mice and rats. It was found that the antibiotic was well absorbed topically so that topical LD50 was approximately the same as intravenous LD50 in mice. The therapeutic effect of nanaomycin A and siccanin against experimental cutaneous Trichophyton mentagrophytes infection in guinea pigs was investigated. Topically applied formulation of nanaomycin A was very effective in improving the condition of lesions and in preventing fungal growth in the infected tissues. Nanaomycin A and siccanin were comparable in activity in experiments.

[Bactericidal effects and combined action of micronomicin with beta-lactam antibiotics against Pseudomonas aeruginosa and Escherichia coli].

Micronomicin (MCR, sagamicin) exhibited bactericidal effects at the lowest concentration among the tested aminoglycoside antibiotics, those were all bactericidal at lower concentrations than that of cefoperazone. When MCR was combined with cefoperazone (CPZ) or piperacillin (PIPC), they showed synergistic activity on checker-board method against Pseudomonas aeruginosa, and they were also synergistic against Escherichia coli when MCR was combined with cefmetazole (CMZ) and cefoxitin (CFX). MCR was synergistic against 40.7% and 44.4% of clinically isolated P. aeruginosa at the fractionary inhibitory concentration (FIC) index 0.5 or less in combination with PIPC and CPZ, respectively. All of the remaining strains of P. aeruginosa were included in the partially synergistic range of FIC index 0.5 to 1. Between MCR and CFX or CMZ, synergy was observed against 63.0% and 88.9% of clinical isolates of E. coli at the FIC index less than 1. Combined effects of MCR and PIPC or CPZ were observed investigating the growing curve of P. aeruginosa, too.

[Effects of prophylactic antibiotic agent on interleukin-6 level in open chest surgery--comparison between imipenem and flomoxef].

Cytokines are known to increase in the patients subjected to open chest surgery. Those patients are usually administered with antibiotic agents for prophylaxis, while some of antibiotic agents might yield significantly higher level of cytokines than other agents especially in patients suffering from severe infections. It is believed that imipenem may yield lower interleukin-6 (IL6) level than cephem antibiotics. To study whether such difference could be observed in the patients who show no sign of severe infections, a total of 13 patients underwent scheduled open chest surgery were allocated at random into two groups, the imipenem-group and the flomoxef-group. The cytokine levels of the patients in the two groups were compared, while the prophylactic administration of imipenem or flomoxef. In both groups, IL6 increased immediately after the operation while endotoxin remained unchanged. Thereafter IL6 decreased gradually in both groups, however, the decrease of IL6 in the imipenem-group was faster and greater than the flomoxef-group resulting in the significantly lower level of IL6 on the 4th day after operation. One week after the operation, there existed no difference in the IL6 levels between these two groups. In conclusion, it was suggested that, depending on the choice of a prophylactic antibiotic agent, some invasive burden could be added to those patients underwent open chest surgery, a certain number of whom would develop severe infection.

[Use of urinary hydroxyproline excretion as a marker of bone metastases in prostatic cancer (1)].

Twenty-four hour urinary hydroxyproline and urinary hydroxyproline creatinine ratio was measured without prior dietary restriction in 24 patients with prostatic cancer and 16 patients with benign prostatic hypertrophy. Both were elevated in patients with prostatic cancer with active bone metastases compared to the values of prostatic cancer without bone metastasis and benign prostatic hypertrophy. In these cases, the values of urinary hydroxyproline creatinine ratio were more reliable. The results show that urinary hydroxyproline creatinine ratio is a very sensitive indicator of active bone metastases of prostatic cancer without dietary restriction.

[Symptoms and signs of benign prostate hypertrophy (BPH)].

Clinical characteristics of BPH were investigated in the relationship among prostate volume estimated by transrectal sonography, symptoms by questionnaire, residual urine volume, and voiding force evaluated by uroflowmetry. There was no apparent relationship among them, which might be caused by the poor reproducibility of residual urine volume, the difficult enumeration of the symptoms, contamination of other diseases of which voiding disorder is correlated with aging and other unknown factors. Under such a situation, this disease should be treated as a BPH syndrome. Moreover we propose that BPH syndrome should be classified into three types; type 1: symptomatic BPH without enlarged prostate, type 2: asymptomatic BPH with enlarged prostate and type 3: symptomatic BPH with enlarged prostate.

[Concentrations of new quinolone agents in serum and prostate tissue].

Twenty five patients with benign prostate hypertrophy were administered ofloxacin (OFLX) simultaneously with norfloxacin (NFLX) in 6 patients, ciprofloxacin (CPFX) in 10, tosfloxacin (TFLX) in 5 and enoxacin (ENX) in 4 patients. The dose of these new quinolones was 100 mg (except 150 mg of TFLX). Their concentrations in the serum and the prostate tissue were measured by high performance liquid chromatography (HPLC). The serum concentration of OFLX was significantly higher than that of NFLX, CPFX, TFLX or ENX. The prostate tissue concentration of OFLX was significantly higher than that of CPFX or TFLX. The ratio of tissue versus serum concentration of each new quinolone agent was not significantly different. The high OFLX tissue concentration appeared to be caused by the high serum concentration.