In vitro and in vivo antipseudomonal activity, acute toxicity, and mode of action of a newly synthesized fluoroquinolonyl ampicillin derivative

Compounds N-(6,7-difluoroquinolonyl)-ampicillin (AU-1) and N-(6-fluoroquinolonyl)-ampicillin (FQ-1), synthesized by coupling of the carboxyl group of 6,7-difluoroquinolone (FP-3) and 6-fluoroquinolone (FP4), respectively, with the alpha-amino-group of ampicillin side chain, exhibit antipseudomonal activity similar to and lower acute toxicity than that of norfloxacin, whereas neither ampicillin nor the fluoroquinolone moieties, compound FP-3 or FP4, alone have such activity. Also, AU-1 and FQ-1 are active against tested clinical isolates of Pseudomonas aeruginosa that are highly resistant to norfloxacin, gentamicin, or both. The therapeutic efficacies of FQ-1 and norfloxacin were assessed and compared in neutropenic mice infected with a 90% lethal dose of P aeruginosa. Mice intraperitoneally administered FQ-1 (10 mg/kg) 4, 8, 24, and 48 hours after infection had survival rates as high as 80%, comparable to those of mice treated with norfloxacin at the same dosage and dosing schedule. The study of protoplast formation revealed that FQ-1 did not inhibit cell-wall biosynthesis but did induce cell filamentation of Bacillus subtilis at a level close to its minimal inhibition concentration. Both AU-1 and FQ-1 were able to intercalate into the double-stranded DNA. However, that FQ-1 lost such activity after it was treated with penicillinase suggests that the lactam-ring structure in ampicillin moiety of FQ-1 was hydrolyzed by penicillinase and that the hydrolyzed structure of FQ-1 does not own DNA-intercalation activity.     

Bronchoscopic evaluation of pulmonary infiltrates following bone marrow transplantation

Mutants of human prothymosin alpha with impaired ability to inhibit yeast Saccharomyces cerevisiae. cerevisiae cell growth were characterized. Two types of prothymosin alpha-inactivating mutations were observed. Mutations that belong to the first type compromised the nuclear entry of prothymosin alpha by affecting its nuclear localization signal. Analysis of subcellular distribution of GFP-prothymosin alpha fusions revealed a bipartite nuclear localization signal that is both necessary and sufficient for nuclear import of the protein in human cells. Mutations of the second type abrogated the inhibitory action of prothymosin alpha through an unknown mechanism, without influencing the nuclear import of the protein.     

Celiac disease

Celiac disease, or gluten-sensitive enteropathy, classically presents as diarrhea and weight loss in childhood, but it may also have protean manifestations and appear well into adult life. The increasing availability of noninvasive blood tests that are highly sensitive and specific for celiac disease enables primary care physicians to recognize the disorder in a wide variety of clinical situations. The authors believe that the disease is more common than supposed and thus offer this diagnostic review to increase awareness.     

Cystoscopic staging of carcinoma uterine cervix, revisited

Of the 378 cases of stage 3 carcinoma uterine cervix, only 10 showed vesical invasion, while 19 of 24 cases of stage 4 disease had vesical invasion. Results of this procedure did not alter the management of the disease in any of these cases. From the whole series it was concluded that cysto-urethroscopy is an unnecessary, cost ineffective, invasive procedure which has no role in either diagnosis or in planning the definitive treatment of carcinoma uterine cervix.     

Characteristics of perceptual grouping in rats

Parametric analysis was made of the characteristics by which proximity and alignment serve as cues for perceptual grouping in rats. Rats were initially conditioned to discriminate a series of horizontal lines from vertical lines. Following training, rats were presented with test stimuli that consisted of bistable arrays of disjunct dots. A grouping cue (greater proximity, greater alignment, or both) was randomly assigned to either the horizontal or vertical orientation. The effectiveness of the cues was based on behavioral responses to the cued orientation. Results indicated that proximity served as a cue for perceptual grouping. The effectiveness of the proximity cue was less for rats than found previously in humans and, unlike humans, diminished with increased stimulus scale. Rats did not respond to alignment cues when used in isolation, although alignment facilitated grouping when used in conjunction with proximity cues. Diminished effectiveness of grouping cues likely reduces object recognition abilities, particularly for complex visual stimuli.     

Cervical meningoceles and myelocystoceles: a unifying hypothesis

We initiated a pilot study of adjuvant hepatic arterial infusion chemotherapy (AHAIC) using 5-fluorouracil (5-FU) and leucovorin. Hepatic arterial infusion ports were placed in 15 consecutive patients undergoing curative resection of colorectal liver metastases. The chemotherapy regimen consisted of a weekly infusion of 5-FU (12 mg m 2 per day) and leucovorin (200 mg m 2 per day) for 12 months. The mean follow-up was 22 months (range 3-62 months, SD 21-37 months). There were no clinical or biological complications related to chemotherapy, except for sharp epigastric burns in four patients immediately after 5-FU infusions. Catheter irreversible occlusions led to early cessation of the treatment in three patients. Four of the 15 evaluable patients developed recurrent disease. The site of relapse was the liver in two patients and extra-hepatic sites in the two remaining patients. Three of these four patients died of their recurrent disease. These results suggest that 5-FU and leucovorin can be combined for AHAIC in a long duration regimen with a very low rate of side-effects. This protocol could be safely employed in a prospective randomized study in combination with 5-FU systemic infusions.