Prevention of oral mucositis due to 5-fluorouracil treatment with oral cryotherapy

INTRODUCTION: One of the most common and important side effects of 5-fluorouracil (5-FU) is mucositis with ulcerations in the oral cavity. We investigated the effects of local cryotherapy on mucositis incidence administrated durng 5-FU treatment. METHODS: In a total of 99 courses, 5-FU and folinic acid combination chemotherapy was given to 40 patients. In our study, we considered every course as a single case, and cryotherapy was given to the same patient in one course but not given in the next. RESULTS: While mucositis developed in 6.7% of the courses given with cryotherapy, this ratio was 38.9% in courses given without cryotherapy. In the logistic regression analysis, development of mucositis had been found to correlate only with cryotherapy. Odds ratio (OR) = 11.5; in the 95% confidence interval (CI) = 3.2 - 41.9; (p = 0.001). DISCUSSION: Results of initial studies evaluating the effects of cryotherapy in preventing mucositis due to 5-FU based chemotherapy regimens were promising. We concluded that oral cooling prevents 5-FU induced mucositis. This effective prophylactic treatment should be used in patients who are at increased risk for developing 5-FU induced mucositis.     

Inherited C8 beta subunit deficiency in a patient with recurrent meningococcal infections: in vivo functional kinetic analysis of C8

A 16 year old with recurrent meningococcal infections is reported. Absence of haemolytic activity in both the classical and alternative pathways resulted from an absence of functional C8. Addition of functional C8 restored hemolytic activity. Antigenically deficient C8 was present in the serum and isoelectric focusing of serum confirmed the absence of the C8 beta chain. Following the infusion of fresh frozen plasma, we followed the decay in C8 functional activity as well as total haemolytic activity. C8 activity peaked at about 3 h with a half-life survival estimated to be 28 h. The kinetics of total haemolytic activity showed a slower decay with an exponential decline over 72 h and a half-life of 55 h. Fresh frozen plasma may be of value in the treatment of patients with C8 deficiency and acute Neisserial infections.     

Rabbit C3: isolation and characterization of reactions in vitro and during in vivo antigen antibody interaction

Rabbit C3 has been identified in serum by agarose gel electrophoresis and by immunoelectrophoresis, and it was shown that calcium ions slow its mobility. It was purified by methods previously used for human C3. Characteristic conversion products similar to those in other species were produced after various in vitro treatments. Reproducible changes occurred during sub-anaphylactic antigenic challenges in the rabbit which were reflected in total serum complement activity. Anaphylactic death was associated with profound changes in haemolytic complement and C3. These findings provide a basis for further study in the rabbit during experimental immunological disease.     

The effects of vitamin A, pentoxyfylline and methylprednisolone on experimentally induced amyloid arthropathy in brown layer chicks.

The effects of vitamin A, pentoxyfylline and methylprednisolone on experimentally induced amyloid arthropathy were investigated. In this study, 175 1-day-old brown layer chicks were used. Throughout the study Group II (vitamin A) received high doses of vitamin A (75,000 IU/kg), whereas Group I (negative control), Group III (positive control), Group IV (pentoxyfylline) and Group V (methylprednisolone) received normal levels of vitamin A in the diet. At the fifth week, the experimental Groups II, III, IV and V were injected with Freund's adjuvant intra-articularly to induce amyloid arthropathy. Group IV received pentoxyfylline and Group V received methylprednisolone (10 mg/kg, intramuscularly) once. Joint and blood samples were examined 13 weeks after the injections. The values in Groups I, II, III, IV and V, respectively, were as follows: amyloid arthropathy formation (%), 0, 100, 87, 76, 66; serum amyloid A (ng/ml), 166+/-17, 607+/-40, 423+/-39, 342+/-27, 293+/-22; serum retinol (microg/dl): 59.75+/-3.8, 42.72+/-3, 59.24+/-3.6, 102+/-9.1, 101.3+/-12.3; heterophil/lymphocyte ratio: 0.504, 0.75, 0.75, 0.087, 0.44. In conclusion, it was observed that vitamin A enhanced the development of amyloid arthropathy and there were positive associations between amyloidosis, increased levels of serum amyloid A and increased numbers of tissue infiltrating macrophages. Methylprednisolone had a more successful inhibitory effect on amyloid arthropathy than pentoxyfylline.     

Acceleration of rat brain beta-adrenoceptor subsensitivity following the coadministration of histamine receptor antagonists with imipramine

Systemic administration of isoprenaline to rats produced a dose-dependent increase in water drinking which was effectively blocked by propranolol. This dipsogenic effect was significantly inhibited by the subacute (4 days) administration of imipramine (18.1. mg/kg/day) together with either the H₁-histamine receptor antagonist, chlorpheniramine (0.1 or 1.32 mg/kg/day), or the H₂-histamine antagonist, cimetidine (1.91 mg/kg/day) or ranitidine (0.60 or 1.51 mg/kg/day). The oral subacute administration of imipramine alone had no significant effect on this behavior. However, chronic ingestion of imipramine alone (21 days) caused a significant reduction in the isoprenaline-induced behavior.It is concluded that the desensitization of central beta-adrenoceptors, as evidenced by inhibition of isoprenaline-induced drinking, can be accelerated following the oral subacute co-administration of imipramine with either H₁- or H₂-histamine receptor antagonists. It also seems that central histamine receptors may partially contribute towards the mechanism of antidepressant effect of imipramine.     

Inhibition of experimental autoimmune encephalomyelitis in Lewis rats by nasal administration of encephalitogenic MBP peptides: synergistic effects of MBP 68-86 and 87-99

Induction of mucosal tolerance by inhalation of soluble peptides with defined T cell epitopes is receiving much attention as a means of specifically down-regulating pathogenic T cell reactivities in autoimmune and allergic disorders. Experimental autoimmune encephalomyelitis (EAE) induced in the Lewis rat by immunization with myelin basic protein (MBP) and Freund's adjuvant (CFA) is mediated by CD4+ T cells specific for the MBP amino acid sequences 68-86 and 87-99. To further define the principles of nasal tolerance induction, we generated three different MBP peptides (MBP 68-86, 87-99 and the non- encephalitogenic peptide 110-128), and evaluated whether their nasal administration on day -11, -10, -9, -8 and -7 prior to immunization with guinea pig MBP (gp-MBP) + CFA confers protection to Lewis rat EAE. Protection was achieved with the encephalitogenic peptides MBP 68-86 and 87-99, MBP 68-86 being more potent, but not with MBP 110-128. Neither MBP 68-86 nor 87-99 at doses used conferred complete protection to gp-MBP-induced EAE. In contrast, nasal administration of a mixture of MBP 68-86 and 87-99 completely blocked gp-MBP-induced EAE even at lower dosage compared to that being used for individual peptides. Rats tolerized with MBP 68-86 + 87-99 nasally showed decreased T cell responses to MBP reflected by lymphocyte proliferation and IFN-gamma ELISPOT assays. Rats tolerized with MBP 68-86 + 87-99 also had abrogated MBP-reactive IFN-gamma and tumor necrosis factor-alpha mRNA expression in lymph node cells compared to rats receiving MBP 110-128 nasally, while similar low levels of MBP-reactive transforming growth factor-beta and IL-4 mRNA expressing cells were observed in the two groups. Nasal administration of MBP 68-86 + 87-99 only slightly inhibited guinea pig spinal cord homogenate-induced EAE, and passive transfer of spleen mononuclear cells from MBP 68-86 + 87-99-tolerized rats did not protect naive rats from EAE. Finally, we show that nasal administration of MBP 68-86 + 87-99 can reverse ongoing EAE induced with gp-MBP, although higher doses are required compared to the dosage needed for prevention. In conclusion, nasal administration of encephalitogenic MBP peptides can induce antigen-specific T cell tolerance and confer incomplete protection to gp-MBP-induced EAE, and MBP 68-86 and 87-99 have synergistic effects. Non-regulatory mechanisms are proposed to be responsible for tolerance development after nasal peptide administration.      

ACE Genotype May Have an Effect on Single versus Multiple Set Preferences in Strength Training

A polymorphic variant of the human angiotensin converting enzyme (ACE) gene was identified. The 'D' (rather than 'I') variant was associated with improvements in strength related to physical training. We set out to determine whether the response to different patterns of strength training might also differ. Ninty-nine Caucasian male non-elite athletes were randomly allocated into one of three groups: 31 non-training/control (CG: 31), single-set (SSG: 35) and multiple-set (MSG: 33). SSG and MSG trained three times a week for 6 weeks. Both training groups were underwent a strength-training program with two mesocycles (12-15 repetition maximum (RM) and 8-12 RM mesocycles). One RM loads in half squat and bench press were assessed before training and after the first and second mesocycles. ACE polymorphisms analysed by polymerase chain reaction (PCR) methods. Subjects with ACE II genotype in the MST group had improved strength development in 12-15 RM, while SST and MST groups had similar gains in 8-12 RM. Subjects with ACE DD genotype in both the SSG and the MSG had similar benefits from both 12-15 RM and 8-12 RM. Strength gains for subjects with ACE ID genotype in the SSG were similar to MSG gains in response to 8-12 RM loads but not with 12-15 RM loads. Additionally, subjects with DD genotype had superior strength gains in both strength training groups. Tailoring strength training programmes (single-set vs. multiple set) according to the athlete's ACE genotype may be advantageous.     

Effect of melatonin in the prevention of post-operative adhesion formation in a rat uterine horn adhesion model

BACKGROUND: Our main aim was to investigate the effects of melatonin (ME), possibly the most powerful free-radical scavenger, on the prevention of i.p. adhesion formation in rat uterine horn. Our secondary aim was to determine whether different methods of administration of ME were beneficial. METHODS: Animals were randomly assigned into seven groups, each consisting of 13 rats. Measured serosal injury was created using a standard technique. While control and two sham groups were not given ME, two of the remaining four groups were given a single dose of 10 mg/kg (2 mg) of ME i.p. immediately after injury and 30 min prior to injury respectively. In the two other groups, ME treatment was continued daily for 5 days. All animals were killed 2 weeks after surgery and adhesions were determined and scored by a examiner blinded to the test. RESULTS: The extent, severity and total scores of adhesion were found to be significantly reduced in all of the ME treatment groups when compared with control and sham groups. There were no statistically significant differences between the treatment groups. CONCLUSIONS: This study showed that even single dose ME therapy was effective in the prevention of post- operative i.p. adhesion formation.     

Neuronal nuclear antigen (NeuN): a new tool in the diagnosis of central neurocytoma

The use of neuronal nuclear antigen (NeuN) as a reliable neuronal marker in the differential diagnosis of clear cell neoplasms of the central nervous system was determined in a biopsy series of 23 cases. Immunohistochemical analyses were carried out by antisera against neuronal nuclear antigen, synaptophysin, neuron-specific enolase, microtubule-associated protein 2, and glial fibrillary acidic protein. All eight central neurocytomas were characteristically immunolabeled by NeuN. NeuN immunoreactivity was uniformly strong and basically located in the nuclei of neurocytes. Despite this uniform staining pattern of central neurocytomas, 12 cases of oligodendrogliomas and three cases of ependymoma were negative for NeuN. As the diagnostic criteria for central neurocytoma include immunohistochemical and/or ultrastructural evidence for neuronal differentiation, NeuN as a sensitive and specific neuronal marker in formalin-fixed, paraffin-embedded tissues may greatly facilitate the differential diagnosis of central neurocytomas.     

Bone marrow transplantation for diamond-blackfan anemia.

Patients with Diamond-Blackfan anemia (DBA) who are unresponsive to or intolerant of corticosteroids, experience treatment failure with other treatments, develop additional cytopenias or clonal disease, or opt for curative therapy are often treated with allogeneic bone marrow transplantation. We studied the transplantation outcomes of 61 DBA patients whose data were reported to the International Bone Marrow Transplant Registry between 1984 and 2000. The median age was 7 years (range, 1-32 years). Among 55 patients with available transfusion information, 35 (64%) had received > or =20 units of blood before transplantation. Most patients (67%) received their bone marrow grafts from an HLA-matched related donor. The median time to neutrophil recovery was 17 days (range, 10-119 days) and to platelet recovery was 23 days (range, 9-119 days). Five patients did not achieve neutrophil engraftment. The 100-day mortality was 18% (95% confidence interval, 10%-29%). Grade II to IV acute graft-versus-host disease occurred in 28% (range, 17%-39%) and chronic graft-versus-host disease in 26% (range, 15%-39%). The 3-year probability of overall survival was 64% (range, 50%-74%). In univariate analysis, a Karnofsky score > or =90 and transplantation from an HLA-identical sibling donor were associated with better survival. These data suggest that allogeneic bone marrow transplantation is effective for the treatment of DBA. Transplantation before deterioration of the performance status and from an HLA-identical sibling donor may improve survival.