Folate synthesized by bacteria in the human upper small intestine is assimilated by the host

BACKGROUND & AIMS: Some intestinal flora are known to synthesize folate. The aim of this study was to determine whether folate synthesized by small intestinal flora is assimilated by the human host. METHODS: Subjects with atrophic gastritis and healthy volunteers were studied before and after omeprazole administration. A double-lumen perfusion tube was placed in the duodenum. 3H-labeled P-aminobenzoic acid, a precursor substrate for bacterial folate synthesis, was perfused. Downstream intestinal aspirates and a 48-hour urine collection were obtained. RESULTS: Atrophic gastritis and omeprazole administration were associated with increases in duodenal pH and in small intestinal flora. Bacterially synthesized folates were isolated from the intestinal aspirates. Tritiated 5-methyltetrahydrofolate, a major metabolite of folate, was isolated from the urine of omeprazole-treated subjects in greater quantities than from drug-free subjects (P<0.01); the quantity of tritiated 5-methyltetrahydrofolate in the urine of the subjects with atrophic gastritis was similarly elevated. CONCLUSIONS: (1) Mild bacterial overgrowth caused by atrophic gastritis and administration of omeprazole are associated with de novo folate synthesis in the lumen of the small intestine; (2) the human host absorbs and uses some of these folates; and (3) the contribution to folate nutriture from this source remains unclear.     

Variation in radiosensitivity due to cell age and split-dose recovery in polykaryons induced by cytochalasin

We have investigated the properties of an in vitro cell survival assay that uses as its endpoint the ability to form polyploid cells (polykaryons) in the presence of cytochalasin B (CB). The criterion for survival is that a polykaryon-forming unit (PFU) must reach the arbitrary DNA content of at least 16C. The age-dependence of PFU sensitivity to 137Cs irradiation was determined using V79-379A cells synchronized at mitosis. Cells assayed as PFUs demonstrated much less variation in radiosensitivity with age than did clonogens, but the changes in curve shape were qualitatively similar. In both assays mitotic cells yielded an exponential survival curve while that obtained at 5 h (mid-late S) had a marked quadratic component. Owing to the small overall variation in PFU survival with age, at doses greater than about 25 Gy the surviving fraction at 5 h was lower than in mitosis. In both V79-379A and HeLa S3 cells, PFUs demonstrated a capacity for split-dose recovery and yielded recovery ratios at 2.6 at 50 Gy in V79 and 1.5 at 20 Gy in HeLa. Since these ratios were much lower than in clonogens at the same dose, we suggest that this is consistent with an association that we have previously demonstrated between PFU response and the clonogenic initial slope. In an attempt to clarify the DNA lesions to which PFUs may be sensitive, we determined PFU response following exposure to 254-nm UV irradiation. In contrast with ionizing radiation, PFU response to UV was very similar to that of clonogens. This suggests that following UV exposure the absence of cytokinesis in polykaryons may confer less protection than in the case of ionizing radiation, possibly due to fundamental differences in the spectrum of DNA lesions produced.     

Rural student clubs and the social responsibility of medical schools

The life expectancy of patients with invasive bladder cancer is limited by the age of incidence and by the natural history of the cancer. Careful selection of patients, independent of age but linked to a neoadjuvant chemotherapy, should be useful for a bladder-sparing policy. Between January 1991 and December 1994, we selected 36 patients with invasive, transitional bladder cancer, but showing good performance status, after a transurethral resection biopsy performed with cytoreductive intention, and after a complete staging. Patients (median age, 65 years) were treated with neoadjuvant M-VAC/M-VEC and then selected for conservative surgery if the downstaging, topography, absence of in situ carcinoma, and residual bladder capacity allowed. At restaging, nine patients (27%) were in complete pathological response; 13 (39%) were in partial pathological response, with a total rate of 67%; and 11 patients (33%) were non-responders, i.e. non-downstaged. Thirty nine percent were treated with radical cystectomy and 60% with limited surgery. Thirteen patients relapsed and seven died of disease during a median follow-up period of 23.5 months. At the end of the study, 68% of patients were alive, with a progression-free survival of 49.8% and a median survival of 32.9 months. Twenty one patients were alive at 31 December 1995, 14 with their bladder. No statistical differences were observed for overall survival and progression-free survival between the two surgery groups. Results were independent of age. A statistically significant difference was found (p = 0.0001) only between non-responders and all the downstaged patients, independent of surgery. These results confirm the feasibility of conservative treatment after a careful selection of patients, even in patients over 65 years, compared with standard available treatments.     

Evaluation of the retinal nerve fiber layer

In normal eyes, the retinal nerve fiber layer (RNFL) is usually best visible in the inferior temporal part of the fundus, followed by the superior temporal region, the nasal superior region and the nasal inferior region. This distribution correlates with the configuration of the neuroretinal rim, the diameter of the retinal arterioles, the location of the foveola, and the lamina cribrosa morphology. With increasing age, the RNFL visibility decreases diffusely without preferring special fundus regions and without the development of localized defects. With all optic nerve diseases, the visibility of the RNFL is decreased in addition to the age-related loss, in a diffuse and/or a localized manner. The localized defects are wedge-shaped and not spindle-like defects, running toward or touching the optic disk border. Typically occurring in about 20% of all glaucoma eyes, they can be found also in other ocular diseases, such as optic disk drusen, toxoplasmotic retinochoroidal scars, longstanding papilledema or optic neuritis due to multiple sclerosis. Since they are not present in normal eyes, they almost always signify an abnormality. RNFL evaluation is especially helpful for early glaucoma diagnosis and in glaucoma eyes with small optic disks. In advanced optic nerve atrophy, other examination techniques, such as perimetry, may be more helpful for following optic nerve damage. Considering its great importance in the assessment of optic nerve anomalies and diseases and taking into account the feasibility of its ophthalmoscopic evaluation using green light, the retinal nerve fiber layer should be examined during any routine ophthalmoscopy.     

Interhemispheric disconnection, Balint''s syndrome and persistent anarthria: Marchifava-Bignami disease with white matter hemorrhage

Percutaneous laser diskectomy has recently been promoted as a viable alternative in treatment of the symptomatic lumbar disk herniation. Careful scrutiny of the literature, including the natural history of low back disorders and results of various surgical techniques in controlled studies, makes it clear that percutaneous laser diskectomy adds little to our surgical armamentarium. As surgeons, we should be encouraged to make treatment decisions in the best interests of our patients, based on unbiased, prospective scientific studies.