Fluconazole sensitivities of Candida species isolated from the mouths of terminally ill cancer patients

BACKGROUND: It has been suggested that tumors respond differently after irradiation with 10 or more fractions than with less fractionated regimens and that extrapolation from experiments with only a few fractions to "curative" regimens may be invalid. To test this hypothesis, we compared hypofractionated-accelerated treatments with "curative" fractionation schedules in human squamous cell carcinoma in nude mice. MATERIAL AND METHODS: FaDu tumors were transplanted subcutaneously into the hindleg of NMRI nu/nu mice. TCD50 values, i.e., the dose necessary to control 50% of the tumors locally, were determined after irradiation under ambient blood flow conditions with 5 and 10 fractions in 5 days, 10 fractions in 10 days, and 30 fractions in 15 days, 6 weeks or 10 weeks. RESULTS: TCD50 values of the hypofractionated regimens were not significantly different and varied from 41 to 46 Gy. The number of fractions given in the same overall time had no measurable effect on local tumor control. The TCD50 after 30 fractions in 6 weeks was 30 Gy higher than after the hypofractionated regimens. This effect was caused by a substantial increase of TCD50 with overall treatment time, the dose recovered per day was 0.82 Gy (95% CI 0.66; 0.96). alpha/beta eff determined from all data was 58 Gy (13; infinite). CONCLUSIONS: The results of the present study compare well with our previous findings after different "curative" fractionation schedules in the same tumor. Thus, our study does not support that tumors respond differently after application of 10 or more fractions compared to less fractionated regimens. The biological mechanisms that govern the radiation response of FaDu tumors appear to be the same for hypofractionated-accelerated and "curative" regimens. Since only one tumor was investigated, these results cannot be generalized at the present time.     

Lumbosacral movement in the sit-and-reach and in Cailliet's protective-hamstring stretch

STUDY DESIGN: This study analyzed movement characteristics of subjects as they performed two different hamstring stretching activities. OBJECTIVES: The study determined if there were differences in lumbosacral movement as the subjects performed the two stretches. SUMMARY OF BACKGROUND DATA: Cailliet contends that his protective hamstring stretch is less apt to be stressful to the structures of the spine than is a more commonly done sit-and-reach stretching activity. No previous biomechanical investigation has tested his contention. METHODS: Lumbosacral movement was measured with an Ady-Hall lumbar monitor as 40 university students (20 males, 20 females) performed a popular sit-and-reach test and a sit-and-reach test that subscribed to Cailliet's protective hamstring stretch protocol. RESULTS: Lumbosacral movement was almost identical in the two stretching activities. CONCLUSIONS: If lumbosacral movement is the only criterion to consider in evaluating the safety of these two stretching activities, it makes little difference which activity is chosen. If moment of inertia were the dependent variable rather than lumbosacral movement, possibly one activity may be less stressful to the structures of the spine than the other.     

Intrachromosomal triplication of 15q11-q13

A 7 year old girl with intrachromosomal triplication 46,XX,-15,+der(15)(pter-->q13::q13-->q11::q11-->qter) resulting in tetrasomy of 15q11-q13 is reported. Fluorescence in situ hybridisation confirmed that the tetrasomic region included the entire segment normally deleted in Prader-Willi and Angelman syndrome patients, and breakpoints were similar to those reported in two tandem duplications of 15q11-q13. The middle repeat was inverted, suggesting a possible origin through an inverted duplication intermediate. Microsatellite analysis showed that the rearrangement was of maternal origin and involved both maternal homologues. Clinical findings included multiple minor anomalies (a fistula over the glabella, epicanthic folds, downward slanting palpebral fissures, ptosis of the upper lids, strabismus, a broad and bulbous tip of the nose, and small hands and feet), motor and mental retardation, a seizure disorder, and limited verbal abilities. In addition, immunological examination disclosed a selective immunodeficiency. The overall phenotype did not clearly resemble that of cases with tetrasomy 15pter-q13 associated with an extra inv dup(15)(pter-->q13:q13-->pter) chromosome. The latter aberration causes more severe mental deficit and intractable seizures, but less marked phenotypic alterations, although some overlap in mild facial dysmorphic features is present. A number of features common to Angelman syndrome were also observed in the patient.     

Efficacy of various therapeutic regimens in eliminating Pasteurella pneumotropica from the mouse

Pasteurella pneumotropica, a gram-negative opportunistic pathogen, can be isolated from the oropharynx, intestinal tract, and reproductive tract of clinically normal mice and has been associated with various clinical syndromes, including conjunctivitis, infections of the reproductive tract, otitis, and subcutaneous abscess formation. Enrofloxacin, a fluoroquinolone bactericidal antimicrobial, has been shown to be effective in eliminating P. multocida from rabbits. We sought to determine whether enrofloxacin would eliminate P. pneumotropica from mice known to be asymptomatically infected with the agent. Pasteurella pneumotropica-positive (culture and immunofluorescence assay) male (n = 55) and female (n = 55) C57BL/6N mice were randomly assigned to one of seven treatment groups or to a control group. These groups were designed to evaluate the efficacy of enrofloxacin administered orally via the drinking water or parenterally at three dosages (8.5, 25.5, and 85.0 mg/kg of body weight per day) over a 14-day treatment period. A tetracycline-treated group (60 mg/kg per day) and an untreated control group were included for comparisons. Repeated oropharyngeal swab and fecal specimens were obtained for culture through posttreatment day 30, and specimens from numerous enteric and reproductive organs collected during necropsy were used to evaluate group differences. Enrofloxacin eliminated evidence of P. pneumotropica from all sites when administered at 25.5 or 85 mg/kg but not at 8.5 mg/kg by either route for at least 30 days after treatment. Tetracycline-treated and control groups remained consistently culture-positive throughout the study. We concluded that the oral route may be a more practical method for treating large numbers of mice. Enrofloxacin may be a practical and inexpensive alternative to cesarian rederivation or embryo transfer for the elimination of P. pneumotropica in mice.     

Adoptively transferred CD4+ lymphocytes from CD8 -/- mice are sufficient to mediate the rejection of MHC class II or class I disparate skin grafts

Recent studies revealed that CD4+ cells initiate allograft rejection through direct recognition of allogeneic MHC class II Ags and indirect recognition of MHC peptides processed by self APCs. Both pathways were shown to help CD8+ cells that eventually lysed allogeneic MHC class I-presenting targets. There was little evidence, however, that CD4+ cells are sufficient for graft rejection. We studied skin graft rejection by CD8-deficient (CD8 -/-) mice. We showed that BALB/cJ(H-2d) CD8 -/- mice could reject allogeneic skin from C57BL/6J(H-2b) mice deficient in MHC class I or in MHC class II Ags. To understand the role of CD4+ cells in this process, we isolated them from CD8 -/- mice and transferred them to BALB/cJ nude mice that had been grafted with allogeneic skin (H-2b) from animals deficient in MHC class I or MHC class II. Nude mice injected with CD4+ cells rejected MHC class II and, albeit more slowly, MHC class I disparate skins. We showed in vitro evidence that CD4+ cells were not cytotoxic toward MHC class I or MHC class II disparate targets and that they recognized MHC class I allogeneic targets through indirect recognition. CD4+ cells produced Th1 cytokines, but not IL-4, following stimulation with allogeneic cells. Furthermore, intragraft TNF-alpha was elevated in skin grafted onto nude mice reconstituted with CD4+ cells compared with nonreconstituted mice. This suggests that MHC class II- or MHC class I-guided CD4+ cells alone are sufficient to induce rejection by the generation of cytokine-induced lesions.     

Functional treatment of patellar dislocation in an athletic population

OBJECTIVE: To determine the clinical applicability of ultrasound-guided detrusor biopsy from the anterior bladder wall and to assess whether it is as representative and as sufficient for determining detrusor ultrastructure as the traditional transurethral biopsy from the lateral bladder wall. MATERIALS AND METHODS: The detrusor structure in 22 biopsies. 11 obtained transabdominally and 11 transurethrally from 11 patients, was evaluated without knowledge of the biopsy method by light and electron microscopy, including morphometric analysis. In addition, several specimens from each of three bladders were evaluated, also 'blindly', for ultrastructural diagnosis of the detrusor in an independent current study of voiding dysfunction in geriatric patients. RESULTS: There were no differences in intercellular distances and cell: nucleus ratios between transabdominal and transurethral biopsies in eight of the 11 patients. Furthermore, ultrasound-guided transabdominal biopsies were as representative of the detrusor as were transurethral biopsies. CONCLUSION: The transabdominal approach is recommended as an easy, relatively inexpensive and efficient method of obtaining biopsies of the detrusor for study of its structure in voiding dysfunction. On the other hand, the observations and diagnoses made by 'blind' qualitative study of several specimens from the same bladder were identical. This, together with the similarity of detrusor structure in the transabdominal and transurethral biopsies, strongly supports the idea that such structure is relatively uniform throughout the entire bladder wall.