A case report: Severe bone marrow suppression caused by 6-mercaptopurin in Crohn's disease patient]

A 23-year-old man was admitted for treatment of acute exacerbation of ileitis and perianal abscess caused by Crohn's disease. After incision and drainage of the abscess, coupled with antibiotic therapy, 6-mercaptopurine (6-MP) was commenced. His white blood cell (WBC) count on day 12 after initiation of 6-MP was not decreased. However, on day 24 he was re-admitted because of severe myelosuppression (WBC: 300/microl), which was complicated by the recurrence of the perianal abscess. Myelosuppression was prolonged and required the administration of granulocyte colony stimulating factor (G-CSF). G-CSF was continued for 17 days to achieve recovery of his WBC count to a normal level.     

The effect of metronidazole on TPN-associated liver dysfunction in neonates

The effect of metronidazole (MNZ) on hepatic dysfunction associated with total parenteral nutrition (TPN) in neonates was investigated. Neonates receiving TPN for more than 2 weeks were divided into three groups. In group 1, TPN was given alone, in group 2, 25 mg/kg/d of MNZ was administered intravenously for the first 2 weeks of TPN, and in group 3, 50 mg/kg/d of MNZ was given for the first 3 weeks of TPN. Several parameters of liver function tests (LFTs) during the first 4 weeks of TPN were compared among these three groups. There was no significant difference of these parameters between group 1 and group 2. Although there was no significant difference of alkaline phosphatase, gamma-glutamyl transpeptidase, direct bilirubin, and total bile acid between groups 1 and 3, transaminase (glutamic oxaloacetic, glutamic pyruvic) of group 3 remained significantly lower than those of group 1. In conclusion, the administration of MNZ 50 mg/kg/d for 3 weeks, at least, prevented the elevation of transaminase during TPN in neonates, suggesting the possible involvement of intestinal anaerobic flora in the pathogenesis of TPN-associated liver dysfunction.     

Babinski-Nageotte syndrome on magnetic resonance imaging

A 70-year-old woman developed left hypoglossal nerve palsy, a right hemiparesis sparing the face, and a typical left Wallenberg's syndrome. These symptoms resulted from a lesion in the left half of the medulla oblongata, suggesting Babinski-Nageotte syndrome, a rare cerebrovascular disease. This is the first case of ischemic infarction in the territory of the left vertebral artery and posterior inferior cerebellar artery demonstrated on magnetic resonance imaging. Severe bilateral lesions of the distal vertebral arteries demonstrated on digital subtraction angiography may have contributed to the development of this syndrome.     

Sequence-dependent Termination of Mammalian DNA Polymerase Reaction by a New Platinum Compound, (–)-(R)-2-Aminomethylpyrrolidine(1,1-cyclobutane-dicarboxylato)-2-platinum(II) Monohydrate

We examined the mechanisms of the inhibition of DNA synthesis by a new platinum compound, (-)-( R )-2-aminomethylpyrrolidine(1,1-cyclobutane-dicarboxylato)-2-platinum(II) monohydrate (DWA-2114R), a derivative of the antitumor drug cis- diamminedichloroplatinum(II) (CDDP), using prokaryotic and eukaryotic DNA polymerases. Preincubating activated DNA with CDDP or DWA-2114R reduced its template activity for prokaryotic and eukaryotic DNA polymerases in a dose-dependent manner. DWA2114R required six times greater drug concentration and two times longer incubation time to show the same decrease of the template activity compared to CDDP. Treatment of primed pUC118 ssDNA templates with the two drugs followed by second-strand synthesis by prokaryotic and eukaryotic DNA polymerases revealed that DWA2114R bound to DNA in a similar manner to CDDP and these adducts blocked DNA elongation by DNA polymerases of eukaryotes as well as of prokaryotes. With these two drugs, the elongations by E. coli DNA polymerase I (Klenow fragment), T7 DNA polymerase and calf thymus DNA polymerase α were strongly arrested at guanine-guanine sequences (GG). Stop bands were also observed at adenine-guanine sequences (AG) guanine-adenine-guanine sequences (GAG) and mono-guanine sequence (G). Calf testis DNA polymerase β was also arrested efficiently at AG, GAG and G, but much more weakly at GG. This pattern was common to DWA2114R and CDDP.     

Clinical evaluation of cefuzonam in pediatrics and a study on the penetration into cerebrospinal fluid

Studies were carried out on the penetration of cefuzonam (L-105, CZON), a new synthetic cephalosporin antibiotic, into cerebrospinal fluid, and on the clinical efficacy against bacterial infections. The results are summarized as follows: Concentrations of CZON in cerebrospinal fluid at 1 hour after intravenous administration of 100 mg/kg in cases of furunculosis of the external canal, encephalitis and mumps meningitis were 0.56 micrograms/ml, 1.44 micrograms/ml and 0.33 micrograms/ml, respectively. Concentrations of CZON in cerebrospinal fluid at 1 hour after intravenous administration of 100 mg/kg in 3 cases of purulent meningitis were 2.80-6.40 micrograms/ml at the acute stage and 0.56-1.45 micrograms/ml even at the recovering stage. Sensitivities of clinically isolated strains to CZON were determined and expressed as MIC. MICs of CZON on Haemophilus influenzae, Escherichia coli, Proteus mirabilis and Klebsiella pneumoniae were similar to MIC's of cefmenoxime (CMX), and lower than those of cefoperazone (CPZ), cefmetazole (CMZ), cefatiam (CTM) and Cefazolin (CEZ). The MIC of CZON on Staphylococcus aureus was similar to those of CEZ, CMZ and CTM, and lower than those of CMX and CPZ. Clinical responses of CZON were good in 2 cases of purulent meningitis, good in 2 cases of pyothorax, excellent in 1 case of septicemia, excellent in 3 cases of urinary tract infections, excellent in 7 cases and good in 3 cases out of 10 cases of pneumonia. Clinical responses of other diseases were excellent in 4 cases of bronchitis, good in 1 case of furunculosis of the external canal, excellent in 1 case of tonsillitis. No side effects nor abnormal laboratory findings were observed except 2 cases of mild diarrhea out of 24 cases.     

Effect of dextran on the stability of isolated, perfused rat heart

Stability of cardiac function and myocardial intracellular ionic composition was examined in the Krebs-perfused isolated rat working heart. Hearts perfused by a conventional Krebs solution showed stable contraction for 2 h, but during this period, intracellular ionic environment (Na, K, Ca) substantially changed. Addition of dextran to the perfusate inhibited, though not completely, this time-dependent deterioration and made the heart less vulnerable to the hypoxia-reoxygenation.     

Stereoselectivity of a potent calcium antagonist, 1-benzyl-3-pyrrolidinyl methyl 2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate

Four enantiomers (3a-d) of the title compound, YM-09730 (3), were synthesized by the reaction of (-)- or (+)-5-(methoxycarbonyl)-2, 6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid (1a or 1b) with (S)- or (R)-1-benzyl-3-pyrrolidinol (2a or 2b). [3H]Nitrendipine binding affinity and coronary vasodilating activity of these compounds were evaluated. The absolute configuration of the most potent enantiomer (3a) with the longest duration was unequivocally determined to be (S)-1,4-dihydropyridine-C4 and (S)-pyrrolidine-C3 (S,S) by X-ray crystallographic study on 3a X HBr as well as 3a X HCl. The configuration of 1a corresponds to R, and the other enantiomers of 3 were respectively determined by chemical correlation. The potency order of the four enantiomers was (S,S)-3a greater than (S,R)-3b greater than (R,R)-3d greater than (R,S)-3c. Latent chiral characters of nifedipine derivatives with the identical ester groups were assigned by comparison of their puckering modes of 1,4-dihydropyridine (DHP) rings with those found in 3a X HCl or 3a X HBr. On the basis of the assignment, it has been revealed that the (S)-DHP nifedipine derivatives possess the synperiplanar carbonyl group at C5. The conformational restriction may be a factor causing stereoselectivity of antagonism.     

Case of severe ulcerative colitis successfully treated with intravenous cyclosporine without high dose corticosteroid]

A 44-year-old women developed marked myopathy one year earlier, when she was treated with intravenous prednisolone for acute severe exacerbation of ulcerative colitis. When she was admitted to our hospital for another severe exacerbation, intravenous cyclosporine A was administered as monotherapy because she could not tolerate corticosteroid. The treatment was successful and she obtained complete remission. Cyclosporine A monotherapy is considered to be a valuable alternative to proctocolectomy for severe ulcerative colitis patients who cannot tolerate corticosteroid.