A Clostridium perfringens hem gene cluster contains a cysG(B) homologue that is involved in cobalamin biosynthesis.

The hem gene cluster, which consists of hemA, cysG(B), hemC, hemD, hemB, and hemL genes, and encodes enzymes involved in the biosynthetic pathway from glutamyl-tRNA to uroporphyrinogen III, has been identified by the cloning and sequencing of two overlapping DNA fragments from Clostridium perfringens NCTC8237. The deduced amino acid sequence of the N-terminal region of C. perfringens HemD is homologous to those reported for the C-terminal region of Salmonella typhimurium CysG and Clostridium josui HemD. C. perfringens CysG(B) is a predicted 220-residue protein which shows homology to the N-terminal region of S. typhimurium CysG. Disruption of the cysG(B) gene in C. perfringens strain 13 by homologous recombination reduced cobalamin (vitamin B12) levels by a factor of 200. When grown in vitamin B12-deficient medium, the mutant strain showed a four-fold increase in its doubling time compared with that of the wild-type strain, and this effect was counteracted by supplementing the medium with vitamin B12. These results suggest that C. perfringens CysG(B) is involved in the chelation of cobalt to precorrin II as suggested for the CysG(B) domain of S. typhimurium CysG, enabling the synthesis of cobalamin.

Studies to determine the usefulness of the zinc clearance test to diagnose marginal zinc deficiency and the effects of oral zinc supplementation for short children.

OBJECTIVE: To evaluate the usefulness of the body zinc clearance test in the diagnosis of marginal zinc deficiency and to estimate the efficacy of oral zinc supplementation on growth in short children. METHODS: Zinc status was evaluated in 30 (19 boys and 11 girls) Japanese children with short stature using the body zinc clearance test. Changes in growth after oral zinc supplementation (ZnSO4,7H2O; 5 mg/kg/day in two divided doses) were studied. RESULTS: Basal serum zinc concentrations were 75.0 +/- 12.7 micrograms/dl and zinc clearance values were 19.1 +/- 5.8 ml/kg/hour in the 30 subjects. The correlation coefficient between serum zinc concentrations and zinc clearance values was as small as -0.36. There were nine cases whose body zinc clearance values were high and serum zinc concentrations were low, indicating definite zinc deficiency. There were nine cases whose body zinc clearance values were high, despite normal serum zinc concentrations, indicating marginal zinc deficiency. The mean height velocity for males was 5.3 cm/year before zinc supplementation and 7.8 cm/year after the therapy; and the mean SD score for height for age improved from -1.85 to -1.53. The mean height velocity for females was 5.1 cm/year before zinc supplementation and 5.9 cm/year after the therapy, and the mean SD score for height for age changed from -2.02 to -2.03. CONCLUSION: The body zinc clearance test was much more useful than serum zinc concentrations in diagnosing marginal zinc deficiency. Oral zinc supplementation improved the height velocity in short males, but not in short females.

Intrathoracic hyperthermochemotherapeutic perfusion for the intrathoracic malignancies in gastric cancer.

BACKGROUND/AIMS: We introduced intrathoracic hyperthermochemotherapeutic perfusion to two patients with intrathoracic lesions in gastric cancer, one patient with pleural dissemination and the other with left lung metastases. MATERIALS AND METHODS: Heated saline containing cisplatin, mitomycin C, and etoposide was circulated through the patient's thorax by a magnetic pump for an hour. RESULTS: The effects of this procedure were estimated complete respose in the former and no change in the latter. There were no complications. While the intrathoracic temperatures were stable between 42.0 and 42.5 degrees C, systemic temperatures measured at esophagus, urinary bladder, pulmonary artery, and tympanic membrane very gradually increased and peaked under 38.6 degrees C. The drug concentration in the perfusate was much lower than the peak plasma concentration, though concentration in the plasma was higher than the peak plasma concentration. CONCLUSIONS: This procedure is one of the preferable methods for treatment of intrathoracic lesions in gastric cancer because of easy temperature control, pharmacological advantage, and lack of side effects.

[Chemohyperthermic peritoneal perfusion and subtotal peritonectomy for peritonitis carcinomatosa in gastroenteric cancer].

A new operative procedure, called subtotal peritonectomy (SP), in combination with chemohyperthermic peritoneal perfusion, was developed for the treatment of peritonitis carcinomatosa in gastrointestinal cancer. SP includes resection of primary lesion, colon, small bowel, spleen, and gall bladder and parietal peritonectomy. Six patients with gastric cancer and two patients with colon cancer underwent these procedures. A great deal of discharge from the peritoneal cavity, an increase in systemic vascular resistance index, and a decrease in central venous pressure represented much decrease in circulatory volume on days 1 to 2 postoperatively. This state improved at 3 to 4 days after operation. Histopathological study revealed multiple peritoneal seedings with negative surgical margins in all patients. There were no related deaths though bleeding, perforation, and abscess occurred in two patients each. One patient died of peritoneal recurrence after one year, but the other have survived.

Prophylaxis with intraoperative chemohyperthermia against peritoneal recurrence of serosal invasion-positive gastric cancer.

Continuous hyperthermic peritoneal perfusion (CHPP) with a solution which contains 30 mg mitomycin C and 300 mg cisplatin has been introduced as a prophylactic treatment for peritoneal recurrence after curative resection of 79 advanced gastric cancers. The control group consisted of 81 patients with advanced gastric cancer who underwent curative surgery during the same period. CHPP was performed for 60 minutes by perfusing MMC- and CDDP-containing saline solutions warmed at 43.5 degrees C by a special CHPP device. In patients with pathologically confirmed serosal invasion-positive tumors, the survival rate of the CHPP group was significantly higher than that of the control group. A survival advantage for stage IV patients was also obtained by CHPP. However, there was no survival advantage between the CHPP group and the control group with serosal invasion-negative tumors. Adverse effects were observed in four patients who underwent CHPP: One developed severe bone marrow suppression, and transient hyperazotemia was observed in the other three. There was no difference in the incidence of mortality and morbidity between the two groups. These results indicate that CHPP is a safe, readily available prophylactic therapy for peritoneal recurrence after gastric cancer surgery.

[Dual arterial infusion chemotherapy, continuous hyperthermic peritoneal perfusion, and total parietal peritonectomy for peritoneal dissemination in gastric cancer--a case report].

A 36-year-old man developed massive ascites, of which cytology proved Class V, and upper gastrointestinal endoscopy disclosed Borrmann type 4 gastric cancer. We performed dual arterial infusion chemotherapy (DAIC) through the celiac axis and superior mesenteric artery, followed by the operation including continuous hyperthermic peritoneal perfusion, total gastrectomy, subtotal colectomy, massive intestinal resection, splenectomy, cholecystectomy, appendectomy, and total parietal peritonectomy (TPP). Ascites disappeared and the CA125 level was normalized by DAIC. This operation was well tolerated. Though the histopathological study revealed multiple peritoneal disseminations on the visceral peritoneum of stomach, small intestine, colon, and parietal peritoneum such as Douglas' pouch, there were denatured cancer cells in the visceral peritoneum to which blood supply under DAIC was distributed. These results suggested the effect of neoadjuvant DAIC and the significance of TPP.

[Treatment with arbekacin of surgical infections by resistant strains of Staphylococcus aureus. Arbekacin Study Group].

The frequency of infection by methicillin-resistant Staphylococcus aureus (MRSA) is high in Japan and control of such strains is urgently needed. Arbekacin (ABK), a semisynthetic aminoglycoside, has potent activity against S. aureus, including resistant strains, and against Gram-negative bacteria as well. For this reason, in surgical infections (which are often caused by more than one bacterium), this drug might be particularly effective. We calculated the MIC and the decrease in the MIC when cultures of 59 resistant strains of S. aureus isolated in our wards at Osaka City University Hospital, contained arbekacin in the medium. We also used the drug to treat 12 infections caused by resistant strains of S. aureus. The MICs of vancomycin had a single peak at 0.5 microgram/ml, and those for ABK had double peaks at 0.5 and 4.0 micrograms/ml. The effect of arbekacin in lowering the MIC of minocycline (MINO) was slight because of the low MIC of MINO. Effects on fosfomycin (FOM), ampicillin, clavulanic acid/ticarcillin, cefotiam, cefuzonam, flomoxef, and imipenem/cilastatin were strong; the peaks were lowered by 1/2(7)-1/2(11). When 1.0 micrograms/ml ABK was present in the medium, the efficacy of FOM was increased enough that, by prediction from the pharmacokinetics of FOM (blood level when given at the usual dose), all but one (2%) of the 47 resistant strains would be eradicated clinically. If 2.0 micrograms/ml ABK were in the medium, all strain would be eradicated, by our calculations. We treated 11 infections and one colonization by resistant strains of S. aureus with ABK and evaluated the response in these cases of infection. Four infections were treated with FOM as well. The clinical efficacy was good in four infections (three patients), fair in four, and poor in three, for an efficacy rate of 36%. All presumed causative bacteria were eradicated in two (18%) of the 11 infections and S. aureus strains were eradicated in three (27%) of the 11 infections. No symptoms of side effects were reported, but blood urea nitrogen and creatinine rose in a 72-year-old woman with duodenal perforation and peritonitis. The MIC levels of ABK were satisfactory, but clinical efficacy for staphylococcal infections caused by resistant strains was unsatisfactory.