A single nocturnal dose of famotidine for the treatment of duodenal ulcer: evaluation of efficacy and safety

The efficacy and safety of a single nocturnal dose of famotidine (40 mg) was evaluated in 30 consecutive patients of duodenal ulcer (DU). Three patients were lost for follow-up and therefore were excluded. The mean age of remaining 27 patients was 34.3 (+/- 9.9) years and male to female ratio was 8:1. The mean size of the DU was 1.21 (+/- 0.79) cm. After a 4-week therapy all patients showed significant improvement and repeat endoscopy in 24 out of 27 patients (89%, 95% confidence interval; 78% to 100%) showed healed ulcer. Clinical assessment of pain relief at 4-week showed significant drop in the mean score of baseline daytime (from 1.85 to 0.13) and baseline nocturnal pain (from 1.70 to 0.10) (p less than 0.0001 and less than 0.0001, respectively). Also shown was the significant decrease in the mean gastrointestinal symptoms score from 5.89 at baseline to only 0.89 at 4-week (p less than 0.0001). Despite that all those who failed to show ulcer healing at 4-week were smokers, logistic regression analysis could not identify smoking or any other risk factors as adverse predictors of ulcer healing. None of the patients experienced significant side effects or adverse reactions. We conclude, that a single nocturnal dose of famotidine is a practical, highly effective and safe approach for the management of DU.     

Replacement of cholesterol gallstones by murideoxycholyl taurine gallstones in prairie dogs fed murideoxycholic acid

The effect of two hydrophilic bile acids, murideoxycholic acid (3 alpha,6 beta-dihydroxy-5 beta-cholanoic acid) and ursodeoxycholic acid, on cholesterol and bile acid metabolism and hepatic pathology and gallstone composition was studied in the prairie dog. Cholesterol gallstones were induced by feeding a diet containing 1.2% cholesterol for 75 days. The animals were divided into six groups, and gallstone regression was studied as follows: groups 2 and 5, chow plus 0.2% cholesterol; groups 3 and 6, chow plus 0.2% cholesterol plus 0.15% ursodeoxycholic acid; groups 4 and 7, chow plus 0.2% cholesterol plus 0.15% murideoxycholic acid. Animals in groups 2 to 4 were killed after an additional 6 wk; animals in groups 5 to 7 were killed after an additional 12 wk. Gallstone dissolution did not occur in any group. The gallstones in groups 2, 3, 5 and 6 were typical cholesterol aggregates, as determined by polarized light microscopy and Fourier transform infrared spectrometry. The gallstones of the murideoxycholic acid group were large, solitary, dark stones that appeared radiopaque under 22 kVp x-ray examination. Scanning electron microscopy showed that in these stones the cholesterol crystals had been replaced by an amorphous material, both within the stone and on the stone surface. Chemical analysis indicated that at the end of 12 wk the calcium/sodium salt of the taurine conjugate of murideoxycholic acid (murideoxycholyl taurine) comprised 70% of the stones; protein, cholesterol and small amounts of other bile salts were also present. In vitro studies confirmed the insolubility of the sodium and calcium salts of murideoxycholyl taurine. These studies indicate that the hydrophilic bile acids, murideoxycholic acid and ursodeoxycholic acid, did not achieve gallstone dissolution under the conditions used. In the animals fed murideoxycholic acid, an insoluble calcium salt of murideoxycholyl taurine replaced cholesterol as the major constituent of gallbladder stones. This is the first example of an insoluble dihydroxy taurine-conjugated bile acid; administration of the unconjugated bile acid induced precipitation of a kind of gallstone not previously reported. The final result was transformation of cholesterol stones to bile salt stones.     

Microvascular corrosion casting of normal tissue, transitional mucosa and adenocarcinoma in the human colon.

The microcirculatory architecture of normal tissue, transitional mucosa and adenocarcinoma of the human colon was investigated with microvascular corrosion casting (MVCC) combined with scanning electron microscopy (SEM). The study showed that the capillaries within the normal mucosa were arranged in a regular hexagonal pattern around the mucosal glands and that the microvessels of transitional mucosa mostly had lost the typical hexagonal pattern and become slightly wider in diameter. The microvessels in the tumor periphery were increased in number and disorganized, and presented large variation in morphology with claw-like formations, widened sinuses, diverticula and appendixoid patterns. Microvessels were lacking in the central areas of tumors. These morphological alterations may serve as additional indicators of tumor development.     

Inhibition by a novel azole antifungal agent with a geranyl group on lanosterol 14 alpha-demethylase of yeast.

AFK-108 (1-[2-(2,4-dichlorophenyl)-2-((2E)-3,7-dimethylocta-2,6- dienyloxy)ethyl]-1H-imidazole) is a new imidazole derivative characterized by a geranyl substituent showing strong antifungal activity. Azole antifungal agents are known to be potent inhibitors of lanosterol 14 alpha-demethylase (P450(14)DM) of fungi. The role of the geranyl group of AFK-108 on interaction of AFK-108 with the target was studied by using Saccharomyces cerevisiae P450(14)DM as the model enzyme. AFK-108 and some of its derivatives bound to oxidized P450(14)DM with one-to-one stoichiometry and inhibited the demethylase activity. AFK-108 derivatives having the longer farnesyl or the shorter prenyl group showed lower affinity than AFK-108 for the enzyme. AFK-108 caused 100% inhibition at the equivalent concentration to P450(14)DM in the reaction mixture (0.07 microM), while the farnesyl derivative inhibited the activity by 60% at the same concentration. AFK-108 interfered with the binding of CO to the ferrous P450(14)DM. However, the interfering effect of the prenyl derivative was lower than that of AFK-108. Another AFK-108 derivative having the saturated 3,7-dimethyloctyl group was also a weaker inhibitor than AFK-108. These experiments suggest that the geranyl group of AFK-108 interacts with the substrate binding site of P450(14)DM that recognises the side chain of the substrate. AFK-108 is the first example of an azole derivative interacting with the side chain recognising region of the substrate binding site of P450(14)DM.     

Anorexia nervosa with neutropenia--response of neutrophils to G-CSF]

A 50-year-old woman with anorexia nervosa was admitted for evaluation of neutropenia (WBC 1,600/microliters). Her bone marrow was gelatinous, and myeloid cells had decreased. Homogeneous substance deposited in the marrow, stained by alcian blue (pH 2.5), indicative of acid mucopolysaccharides. CFU-G and CFU-GM were decreased in number and myeloid pool in the bone marrow also decreased. Anti-neutrophilic antibody was negative. Neutropenia may be related to myeloid hypoplasia, due to increase of acid mucopolysaccharides replacing adipose cells in the bone marrow under long-term mal-nutritional state. Neutrophils markedly increased by administration of rhG-CSF 5.0 micrograms/kg/day for 14 days without the first peak. Serum G-CSF level did not increase (less than 60 pg/ml). It is effective to administer G-CSF to anorexia nervosa with neutropenia.     

Visual integration of data and basic motor skills under laparoscopy

Background: The qualities of visual perception and of motor reaction to the visual stimulus have never been studied in reference to the type of video-camera system (2-D vs 3-D) used during laparoscopy. Methods: The study was designed in two parts. The first evaluated the ability of the eye to discriminate how objects are spaced relative to one another. The second investigated the motor reaction to the visual stimulus in an environment where depth was the preponderent cue. The tests were performed in a pelvi-trainer in which were inserted different modules built either for visual observation (Part 1) or for evaluation of motor ability (Part 2). Variables studied during Part 1 were the time required to do the test and the number of errors committed during its performance. The variable evaluated during Part 2 was the time needed to terminate the test. Each of these two parts of the study were completed alternating the 2-D and 3-D systems. A total of 304 observations were recorded. Statistics used were the paired t-test, the independent group t-test, and the Newman-Keuls multiple comparisons test. Results: Results of Part 1 of the study confirm that visual perception varies significantly among individuals (n = 10) (p < 0.05) and that a true 3-D video-camera system facilitates visual perception when compared to a 2-D system (p < 0.001). Results of Part 2 of the study also show significant differences among participants (n= 9) (p < 0.05). The true 3-D system allowed significantly faster motor performances than the 2-D system (p < 0.001). Conclusion: Our experiment shows that the 3-D system allowed significant improvements in the execution of the evaluated parameters. Also noted were significant differences among participants in term of visual and motor skills.