Effects of a Cereal Bar with a Combination of Phytoestrogens on the Climacteric Symptoms: A Placebo-Controlled, Randomized Trial.

OBJECTIVE: This study evaluated whether the consumption of a cereal bar combining different phytoestrogens could contribute to the reduction of climacteric symptoms in women. METHODS: This is a clinical, prospective, randomized, simple-blind trial. Forty-eight women, aged 40-65 years, with climacteric symptoms, from a city in southwestern Paraná, Brazil. Participants were randomly assigned into two groups; Phytoestrogens group (PHY = 24), which received for 90-day period a cereal bar containing 80.73 milligrams of soybean and flaxseed phytoestrogens, and the placebo group (PLA = 24), which consumed rice flakes biscuit. Clinical, sociodemographic and anthropometric data were collected and climacteric symptoms were assessed using the Kupperman Index (KI). RESULTS: Forty-three women were analyzed (PHY = 21 and PLA = 22). There were significant reductions in the overall KI score in both groups at the end of the intervention period (p < 0.05). However, the comparison between the groups using linear regression models presented expressively better symptom improvement in the PHY group -6.43 over time (95% CI: -11.6; -1.26; p < 0.05) KI points, with perimenopausal -15.15 (95% CI: -28.95; -1.35) and postmenopausal women -19.34 (95% CI: -33.68; -4.99) showed considerably greater reductions in symptoms at the end of the intervention period compared to premenopausal women. There was also significant reduction in symptoms of hot flushes, paresthesia, sexual complaints, insomnia and melancholy. CONCLUSION: The consumption of a cereal bar containing phytoestrogens was able to improve the symptoms of climacteric syndrome.

Clodronate exerts an anabolic effect on articular chondrocytes mediated through the purinergic receptor pathway.

OBJECTIVE: Bisphosphonates are commonly used anti-osteoporotic drugs which have controversial effects on joint diseases including osteoarthritis. Certain bisphosphonates have been shown to have anabolic effects on cartilage which could have important ramifications for their proposed effects in vivo; however, the underlying mechanisms are poorly understood. Thus, the purpose of this study was to characterize the effects of clodronate on primary articular chondrocyte metabolism and to determine the underlying signaling pathways responsible. DESIGN: The effects of clodronate and pamidronate on extracellular matrix (ECM) biosynthesis, accumulation and MMP-13 activity were observed in high density, 3D cultures of bovine articular chondrocytes for up to 4 weeks were evaluated. Mechanisms were delineated by measuring intracellular Ca(2+) signaling and the effects of pharmacologic inhibition of the purinergic receptor pathway. RESULTS: Clodronate (100 µM) induced an anabolic effect (increased biosynthesis by 13-14%) which resulted in an 89-90% increase in ECM accumulation after 4 weeks of culture and without an associated effect on matrix turn-over. Stimulation by clodronate resulted in a 3.3-fold increase in Ca(2+) signaling and pharmacological inhibitor experiments suggested that the anabolic effects exerted by clodronate are transduced through the purinergic receptor pathway. CONCLUSIONS: These findings support the previous notion that certain bisphosphonates may be useful as adjunctive therapies to potentially ameliorate progression of cartilage degeneration and improve arthritis management.

Network topology for the formation of solvated electrons in binary CaO-Al2O3 composition glasses.

Glass formation in the CaO-Al2O3 system represents an important phenomenon because it does not contain typical network-forming cations. We have produced structural models of CaO-Al2O3 glasses using combined density functional theory-reverse Monte Carlo simulations and obtained structures that reproduce experiments (X-ray and neutron diffraction, extended X-ray absorption fine structure) and result in cohesive energies close to the crystalline ground states. The O-Ca and O-Al coordination numbers are similar in the eutectic 64 mol % CaO (64CaO) glass [comparable to 12CaO·7Al2O3 (C12A7)], and the glass structure comprises a topologically disordered cage network with large-sized rings. This topologically disordered network is the signature of the high glass-forming ability of 64CaO glass and high viscosity in the melt. Analysis of the electronic structure reveals that the atomic charges for Al are comparable to those for Ca, and the bond strength of Al-O is stronger than that of Ca-O, indicating that oxygen is more weakly bound by cations in CaO-rich glass. The analysis shows that the lowest unoccupied molecular orbitals occurs in cavity sites, suggesting that the C12A7 electride glass [Kim SW, Shimoyama T, Hosono H (2011) Science 333(6038):71-74] synthesized from a strongly reduced high-temperature melt can host solvated electrons and bipolarons. Calculations of 64CaO glass structures with few subtracted oxygen atoms (additional electrons) confirm this observation. The comparable atomic charges and coordination of the cations promote more efficient elemental mixing, and this is the origin of the extended cage structure and hosted solvated (trapped) electrons in the C12A7 glass.

Variation in floral longevity in the genus Leptosiphon: mating system consequences.

Pollination or fertilisation trigger floral senescence in a wide range of flowering plants, and yet little attention has been given to the implications of this phenomenon to mating system evolution. We examined the effects of pollination on floral senescence in the genus Leptosiphon. Species in the genus exhibit a wide range of breeding systems. In all cases, compatible pollination induced senescence; emasculated flowers lived longer than hand-outcrossed flowers. In the self-compatible species, Leptosiphon acicularis and L. bicolor, and in one highly selfing population of L. jepsonii, unmanipulated flowers had reduced longevity compared to emasculated flowers, suggesting that autonomous self-pollination limits floral longevity in these species. Limited floral longevity in these highly selfing taxa may reduce opportunities for male outcross success, representing a possible source of selection on the mating system. In turn, the mating system might influence how selection acts on floral longevity; obligately outcrossing taxa are expected to benefit from longer floral longevities to maximise opportunities for pollination, while selfing taxa might benefit from earlier floral senescence to reduce resource expenditure. Overall, the longevity of unpollinated flowers increased with the level of outcrossing in the genus Leptosiphon. Our results taken together with those of a previous study and similar results in other species suggest that floral longevity may represent a largely unexamined role in mating system evolution.

Assessment of the systemic effects of low-level laser therapy (LLLT) on thyroid hormone function in a rabbit model.

The aim of this study was to assess the effects of low-level laser therapy (LLLT) applied to a dental extraction socket on thyroid gland function in a rabbit model, based on serum triiodothyronine and thyroxine levels. Sixteen male New Zealand rabbits were randomly distributed into two groups: a control group (non-irradiated animals) and an experimental group (irradiated animals: one irradiation point in the extraction socket of the lower incisor). Animals in the experimental group were irradiated with an aluminium gallium arsenide diode laser (AlGaAs; wavelength 830 nm, 40 mW, CW laser), for 13 days, every 48 h, at a dose of 6 J/cm(2) per session, resulting in a total dose of 42 J/cm(2). Serum triiodothyronine and thyroxine levels were measured in both groups before extraction and on the last day of observation (day 15). There were no statistically significant differences between the groups in pre- and post-irradiation triiodothyronine and thyroxine values. With the irradiation protocol used in this study, LLLT did not affect thyroid function in rabbits as assessed by circulating serum triiodothyronine and thyroxine levels.

The utility of PEG3350 without electrolytes for 2-day colonoscopy preparation in children.

OBJECTIVES: Successful colonoscopy preparation requires a method which is easy to administer. Simplifying this technique would be useful for adult and pediatric gastroenterologists. Most cleanout agents are not well tolerated by children. Polyethylene glycol without electrolytes (PEG3350 without electrolytes) has been used for constipation and bowel cleanout, but has not been studied as 2-day preparation for colonoscopy in children. This study evaluates the dosing, effectiveness and satisfaction with PEG3350 without electrolytes as a 2-day cleanout for colonoscopy preparation in children. METHODS: Parents of patients aged 5 years or older undergoing colonoscopies were approached for participation. All caretakers received standard instructions with a suggested food handout and a diary to track the doses of PEG3350 administered and to document other adjunct measures (suppository, enema). On the procedure day, parents and children completed appropriate satisfaction questionnaires. Post procedure, the physician rated the visualization of the mucosa. A pediatric gastroenterologist investigator and a second blinded pediatric gastroenterologist assessed the effectiveness using standard procedure photos. RESULTS: 30 patients aged 5-16 years were recruited (15 males, 15 females). The majority of parents and children reported being "very satisfied" or "satisfied" with the preparation. The preparation was rated by the principal investigator and independent pediatric gastroenterologist as effective in all cases. The mean number of doses was 4.7 on Day 1 and 4.9 on Day 2. The average dose given was 1.90 g/kg/day. CONCLUSION: PEG3350 without electrolytes appears to be safe, effective, and well tolerated as a 2-day clean out for colonoscopy preparation in children with an average dose of 1.90 g/kg/day.

Etanercept plus narrowband ultraviolet B phototherapy of psoriasis is more effective than etanercept monotherapy at 6 weeks.

BACKGROUND: A substantial portion of patients with psoriasis does not achieve a satisfactory response under antitumour necrosis factor (TNF)-α biological therapies. OBJECTIVES: We aimed to evaluate whether etanercept plus narrowband ultraviolet B (NB-UVB) phototherapy is superior to etanercept monotherapy in the management of psoriasis. METHODS: In this prospective study, patients with psoriasis were treated with etanercept 25 mg twice weekly. Two marker lesions were selected for determination of the modified Psoriasis Area and Severity Index (M-PASI). NB-UVB was administered thrice weekly whereby one marker lesion was covered as nonirradiated control. Skin biopsies for histology and immunohistochemistry were performed in both marker lesions after a 6-week treatment course. RESULTS: After 6 weeks of therapy, the relative M-PASI reduction (mean ± SD) in etanercept-treated sites (53·7 ± 36·9%) was significantly lower than the reduction in etanercept plus NB-UVB-treated lesions (64 ± 27·8%; P = 0·011). At the end of treatment, histology scores of etanercept-treated psoriatic plaques were significantly higher than scores of etanercept plus NB-UVB-treated sites (4·6 ± 2·7 vs. 3·7 ± 2·4; P =0·045). Epidermal immunoreactivity for CD1a, CD4 and CD8 was significantly lower in etanercept plus NB-UVB-treated lesions when compared with etanercept monotherapy. CONCLUSIONS: Etanercept combined with NB-UVB is more effective than etanercept monotherapy at 6 weeks as demonstrated at a clinical, histological and immunohistological level. However, as there is an increased risk for malignancy by treatment with TNF-α blockers alone or in combination with phototherapy, we recommend to restrict this highly effective combination to short periods of time, for instance to obtain a quicker response, and to avoid long-term treatment.

Hyoscyamine biosynthesis in Datura stramonium hairy root in vitro systems with different ploidy levels.

Hyoscyamine biosynthesis in Datura stramonium hairy roots with different ploidy levels was investigated. For the first time, we report that hairy roots undergo endoreduplication and therefore consist mainly of cells with doupled sets of chromosomes of primary plant tissues, used for Agrobacterium transformation. The alkaloid profiles of hairy roots obtained from diploid and tetraploid plants were similar in terms of the major compounds, but they differed significantly with respect to the minor compounds (here defined as those that accounted for <1% of the total ion current of the alkaloid mixture in gas chromatography-mass spectrometric analyses). Significant differences in the effects of the main nutrients on the growth of the hairy roots obtained from diploid and tetraploid plants and their hyoscyamine contents were observed. The maximal yield of hyoscyamine (177 mg/L) was obtained when hairy roots from tetraploid plants were cultivated in Murashige-Skoog nutrient medium supplemented with 6% sucrose. Time courses of utilization of the main nutrients in the medium during cultivation of D. stramonium hairy root cultures are also presented.

Balancing the risks and the benefits of local fish consumption in Bermuda.

Fish consumption today is widely recognized as highly beneficial since it constitutes a good source of several essential nutrients, such as selenium and polyunsaturated fatty acids (n-3 PUFA). However, fish can also contain contaminants such as mercury, which make the consumer, especially pregnant women, confused about the risk-benefit balance associated with fish consumption. This is particularly true for tropical fish species for which little information is available. We have previously reported that some Bermudian neonates had elevated mercury in their umbilical blood compared with international guidelines. The objective of this study was to give precise and balanced information on the content of mercury, selenium and PUFA in the most consumed fish species in Bermuda. In 2003 and 2006, a total of 307 fish were collected from 43 fish species and 351 samples were analysed (305 flesh samples, 44 liver samples, one roe and one fat sample) by inductively coupled plasma-mass spectrometry (ICP-MS) (metals) and high-resolution gas chromatography (HRGC) (fatty acids). Results show that mercury varies among species from 0.03 to 3.3 microg g(-1) and that it is possible for at-risk groups such as pregnant women to make informed choices concerning fish consumption, e.g. maximizing fish species rich in nutrients and low in mercury.

The effect of landfill leachate composition on organics and nitrogen removal in an activated sludge system with bentonite additive.

A pre-denitrification activated sludge system (AS) without internal recycle was used in lab-scale studies of landfill leachate treatment. A bentonite supplement at a ratio of 1:4 (mineral : biomass) was used to ensure high sludge settling levels and to serve as a micro-organisms carrier. The system was operated within different parameters such as hydraulic retention time (HRT), ammonia loading rate (ALR) or external recycle ratio, which was adapted to treat varying leachate concentrations of COD and ammonia, ranging from 1020 to 2680 mgO(2)l(-1) and 400-890 mgNH(4)-Nl(-1) respectively. The nitrification was complete and ammonia oxidation reached 99%; this was obtained while the ALR did not exceed 0.09 g NH(4)(+)-Ng(-1)MLVSS d(-1) and HRT was not lower than 1 day (in the aeration reactor). The performance of denitrification was successfully improved by controlling the external recycle rate, when the BOD(5)/N ratio in the raw leachate was 4.1. Consequently, N-removal of up to 80% was achieved. A 10-fold decrease in the denitrification rate was obtained at a BOD(5)/N ratio of 0.5. The efficiency of COD removal varied significantly from 36% to 84%. The positive effect of bentonite addition was determined and is discussed based on preliminary studies. The experiments were carried out in fill-and-draw activated sludge with bentonite; the biomass ratio was 1:2. The activated sludge with bentonite was fed with a synthetic high ammonia and organic-free medium.

[Postural biofeedback and locomotion reeducation in stroke patients]. / Barobiofeedback et rééducation de la marche de l'hémiplégique.

AIMS: To compare, in post-acute hemiparetic patients, gait improvement after conventional physical therapy alone or with a specialised balance retraining program. PATIENTS: Twenty-six patients within 3 months of onset of stroke were randomised to receive physical therapy (control group) or therapy and retraining (experimental group), most of the patients in both groups with left hemiplegia. The experimental group was significantly older than the control group. METHOD: Thirteen patients received early conventional therapy, and 13 received therapy combined with standing balance training by biofeedback (BPM Monitor). Clinical measures were collected at entry (J0), once when subjects began to walk (JM) and 30 days later (JM + 30). Gait spatiotemporal parameters were collected by use of the Vicon system at JM and JM + 30. RESULTS: Whatever the method of rehabilitation, the clinical scores improved significantly between J0 and JM + 30, except for spasticity. The time between stroke and the beginning of walking was not significantly different between both groups. Gait velocity increased significantly between JM and JM + 30 in both groups, with no difference between groups. The walking pattern was improved for both groups, with a significant increase of the duration of the paretic limb single stance. The experimental group significantly improved the duration of the reception double stance on the paretic limb between JM and JM + 30 compared with the control group (P = 0.03). CONCLUSION: Both groups demonstrated improvement in the rehabilitation unit. The benefits of visual biofeedback by forceplate system training suggest particular improvement of anticipation equilibrium with conventional therapy.

Role of nitric oxide in the ethylcholine aziridinium model of delayed apoptotic neurodegeneration in vivo and in vitro.

The involvement of nitric oxide in neurodegenerative processes still remains incompletely characterized. Although nitric oxide has been reported to be an important mediator in neuronal degeneration in different models of cell death involving NMDA-receptor activation, increasing evidence for protective mechanisms has been obtained. In this study the role of nitric oxide was investigated in a model of NMDA-independent, delayed apoptotic cell death, induced by the neurotoxin ethylcholine aziridinium ethylcholine aziridinium both in vivo and in vitro. For the in vivo evaluation rats received bilateral intracerebroventricular injections of ethylcholine aziridinium (2nmol/ventricle) or vehicle. In the hippocampus a transient decrease in nitric oxide synthase activity occurred, reaching its lowest levels three days after ethylcholine aziridinium treatment (51.7+/-9.8% of controls). The decrease coincided with the maximal reduction in choline acetyltransferase activity as marker for the extent of cholinergic lesion. The effect of pharmacological inhibition of nitric oxide synthase was tested by application of various nitric oxide synthase inhibitors with different selectivity for the nitric oxide synthase-isoforms. Unspecific nitric oxide synthase inhibition resulted in a significant potentiation of the loss of choline acetyltransferase activity in the hippocampus measured seven days after ethylcholine aziridinium application, whereas the specific inhibition of neuronal or inducible nitric oxide synthase was ineffective. These pharmacological data are suggestive for a neuroprotective role of nitric oxide generated by endothelial nitric oxide synthase. In vitro experiments were performed using serum-free primary neuronal cell cultures from hippocampus, cortex and septum of E15-17 Wistar rat embryos. Ethylcholine aziridinium-application in a range of 5-80microM resulted in delayed apoptotic neurodegeneration with a maximum after three days as confirmed by morphological criteria, life-death assays and DNA laddering. Nitric oxide synthase activity in harvested cells decreased in a dose- and time-dependent manner. Nitric oxide production as determined by measurement of the accumulated metabolite nitrite in the medium was equally low in controls and in ethylcholine aziridinium treated cells (range 0.77-1.86microM nitrite). An expression of inducible nitric oxide synthase messenger RNA could not be detected by semiquantitative RT-PCR 13h after ethylcholine aziridinium application. The present data indicate that in a model of delayed apoptotic neurodegeneration as induced by ethylcholine aziridinium neuronal cell death in vitro and in vivo is independent of the cytotoxic potential of nitric oxide. This is confirmed by a decrease in nitric oxide synthase activity, absence of nitric oxide production and absence of inducible nitric oxide synthase expression. In contrast, evidence for a neuroprotective role of nitric oxide was obtained in vivo as indicated by the exaggeration of the cholinergic lesion after unspecific nitric oxide synthase inhibition by N-nitro-L-arginine methylester.

Correlating the molecular electrostatic potentials of some organic peroxides with their antimalarial activities.

The molecular electrostatic potentials (MEPs) of artemisinin (also known as qinghaosu), yingzhaosu A, and some synthetic analogues have been calculated and studied as a means of distinguishing between high and low antimalarial activity. To facilitate comparison, the dimensionality of the MEP was reduced by Kohonen Neural Network transforms. The reduction revealed that peroxides exhibiting high antimalarial activity are characterized by a continuous strip of negative electric potential surrounding the molecule, whereas peroxides of lesser activity show a broken strip.

Relationship between the response to influenza vaccination and the nutritional status in institutionalized elderly subjects.

BACKGROUND: Influenza is a major health problem among elderly people in industrialized countries. Nursing homes may be a particularly good setting for outbreaks of influenza. Thus, the aim of the present study was to evaluate some aspects of the nutritional status of institutionalized elderly subjects in relation to their response to influenza vaccination. Certain aspects of the cellular immune response were also investigated. METHODS: Twenty-three patients participated in this cross-sectional study. All patients were vaccinated on day 0 with FluviralR, 1994-95 preparation: A/Shangdong/09/93, A/Texas/36/91, B/Panama/45/90. At the same time the prevaccination antibody titer, the nutritional status by the Mini Nutritional Assessment, biochemical parameters, and lymphocyte proliferation were assessed. On day 28, the postvaccination antibody titer was determined. The determination of pre- and postvaccination antibody titers against the various influenza antigens was carried out by the hemagglutination inhibition test. An increase of 4x for any of the virus antigens was considered as a seroconversion. A titer higher than 40 at the prevaccination period was considered as protective. RESULTS: Eleven elderly subjects were responsive and 12 were not. We have shown that the nutritional parameters such as hemoglobin, hematocrit, total protein, iron and vitamin E levels, as well as the DHEA level and the cellular immune response were significantly lower in the nonresponsive group as compared to the responsive group. Thus, they might be associated with the influenza vaccine responsiveness of institutionalized elderly subjects. CONCLUSIONS: These results will help design intervention studies for improving the immune response by achieving an optimal nutritional status, mainly in the frail elderly population, that could have a great public health impact.

Prophylactic intravenous administration of caffeine and recovery after ambulatory surgical procedures.

OBJECTIVE: To determine whether prophylactic intravenous administration of caffeine, to daily caffeine users, decreases the frequency of postoperative headache and shortens recovery time. DESIGN: The study was a prospective, randomized, double-blind investigation with predetermined sample size and statistical power. MATERIAL AND METHODS: After Mayo Institutional Review Board approval and informed consent were obtained, 300 adult ambulatory surgical patients were enrolled in this study, which included randomization to receive either placebo or caffeine (200 mg intravenously) in the postanesthesia care unit. While recuperating, patients were allowed their choice of postoperative beverages. Before dismissal, patients completed a questionnaire providing details about intake of caffeine and tobacco, history of headache, and demographic data. Patients were considered "at risk" for symptoms of caffeine withdrawal if they did not drink a caffeinated beverage after the surgical procedure. RESULTS: Completed questionnaires were obtained from 234 patients. Patients at risk for symptoms of caffeine withdrawal were less likely to have a postoperative headache if they received caffeine intravenously rather than placebo-10% versus 23% (P < 0.05). Time until recovery was not significantly different between caffeine and placebo study groups. CONCLUSION: We conclude that prophylactic intravenous administration of caffeine was beneficial for those patients at risk for symptoms of caffeine withdrawal. For patients who consume caffeinated beverages on a daily basis, we recommend prophylactic administration of caffeine on the day of an ambulatory surgical procedure and anesthesia.

The effects of prolonged treatment with citicoline in temporary experimental focal ischemia.

Potential therapeutic effects of cytidine 5-diphosphocholine (citicoline), a key intermediary in the biosynthesis of the membrane phospholipid, phosphatidylcholine, are presumably related to enhanced phospholipid synthesis in the ischemic brain. We evaluated prolonged citicoline treatment in a temporary focal ischemia model. Using the suture occlusion model, we induced 2 hours of temporary ischemia in 30 Sprague-Dawley rats. The rats were randomly and blindly assigned to receive intraperitoneally 500 mg/kg citicoline (HD), 100 mg/kg citicoline (LD) or physiologic saline as the control group once daily for 7 days (n = 10 per group) beginning at the time of reperfusion. Neurological scoring (0-5 scale) was performed daily. After elective sacrifice on day 7, or earlier if death occurred prematurely, the brains underwent 2,3,5-triphenyltetrazolium chloride (TTC) staining for calculation of corrected infarct and edema volume. The mean corrected infarct volume in the HD group was 125 +/- 45.2 mm3 (mean +/- SD), significantly smaller than controls, 243.5 +/- 88.6 mm3 (p < 0.01, Scheffe's-test). The LD group infarct volume was 200.2 +/- 62.8 mm3 (N.S.). The mean amount of brain edema in the HD group was 46.4 +/- 45.6 mm3 was smaller than the controls, 92.3 +/- 54.4 mm3 and the LD group, 84.9 +/- 71.7 mm3 (N.S.). Mortality before day 7 in the HD was 30% while it was 50% in the two other groups. The neurologic score on day 7 was 2.5 +/- 1.8 in the HD group, 3.3 +/- 1.8 in the LD group and 3.4 +/- 1.7 in controls (N.S.). These results demonstrate that extended high dose citicoline treatment significantly reduced infarct volume in this temporary focal ischemia model and that there was a trend toward reducing brain edema and mortality. These effects may be related to membrane stabilization and inhibition of free fatty acid release.

Faecal incontinence with transitory absence of anal contraction in two sexually or physically abused women.

OBJECTIVE: To report two cases of faecal incontinence caused by transitory absence of anal voluntary contraction without anal anomalies. PATIENTS: Two women referred to our gastroenterology department with faecal incontinence. One patient had been sexually abused by her father; the other had been physically abused by her husband. RESULTS: Clinical and manometric anal contraction was absent despite normal anal endosonography and normal electrophysiological perineal study. Anal contraction was completely normalized after biofeedback, and the patients recovered from the faecal incontinence. CONCLUSION: Transitory absence of anal contraction is very uncommon as the origin of faecal incontinence. It was observed in two abused women.

Hypersensitivity reactions to chemotherapy agents in patients receiving chemoimmunotherapy with high-dose interleukin 2.

BACKGROUND: Treatment with the immune system modulator interleukin 2 (IL-2) can result in a number of immunologic abnormalities ranging from suppression of delayed-type hypersensitivity responses and neutrophil activity to autoimmune thyroiditis and hypersensitivity reactions against iodine-containing radiographic contrast media. There are a number of published reports of chemoimmunotherapy using IL-2 in combination with various chemotherapeutic agents to treat patients with certain cancers, but none have described hypersensitivity responses to the chemotherapeutic agents given. PURPOSE: In the early stages of an ongoing clinical trial of the efficacy of combination chemoimmunotherapy for the treatment of patients with metastatic melanoma, we discovered that a number of the patients experienced unexpected hypersensitivity reactions after receiving chemotherapy. We therefore decided to examine these hypersensitivity reactions in detail. METHODS: During the period of March 1993 through February 1994, 31 patients with metastatic melanoma were treated either by chemotherapy (dacarbazine, cisplatin, and tamoxifen) or by chemoimmunotherapy (the same drug regimen plus interferon alfa and high-dose IL-2). Twelve patients were treated in a non-randomized pilot study, with six receiving chemotherapy and six receiving chemoimmunotherapy. The six patients who received chemotherapy also received carmustine (BCNU). Nineteen subsequent patients were treated in a prospective, randomized study to compare the two therapeutic approaches. In total, 15 of the 31 patients were treated by chemotherapy alone, and 16 were treated by combination chemoimmunotherapy. Overall, the patients in the two groups were balanced in terms of age, sex, and stage of disease. RESULTS: Ten of 16 chemoimmunotherapy patients exhibited type I hypersensitivity reactions during chemotherapy administration, ranging from pruritus, erythema, and edema to hypotension with hemodynamic instability that required pressor therapy. None of the 15 patients on the chemotherapy regimen exhibited hypersensitivity reactions. All patients in the chemoimmunotherapy group gained weight and had elevated white blood cell and eosinophil counts during chemotherapy; these effects were more prominent in those with hypersensitivity reactions. CONCLUSIONS: Hypersensitivity reactions occurred within several hours after chemotherapy administration in patients who had previously received one to two cycles of high-dose IL-2, suggesting that prior IL-2 therapy sensitized patients to cisplatin or dacarbazine. This is the first report of IL-2-induced hypersensitivity to chemotherapy agents.

Nutrients, body composition and exercise are related to change in bone mineral density in premenopausal women.

This study determined relationships among total energy intake, nutrient intake, body composition, exercise group status, and annual rates of change (slopes) in bone mineral density in 66 Caucasian premenopausal women (mean age, 34.4 +/- 2.7) taking calcium supplements. Body composition components measured by dual-energy X-ray absorptiometry included fat mass, soft tissue lean mass, and bone mineral density (g/cm2) of total body, spine (lumbar vertebrae 2-4), and three femur sites measured at baseline, 5, 12, and 18 mo. Nutrients were not significant variables in regression models predicting bone mineral density slopes (rates of change) at any femur site. The only significant variable in models predicting Ward's triangle bone mineral density slope was the initial fat mass and, for trochanter, exercise. Significant variables (P < 0.05) in models predicting total body bone mineral density slope included the initial fat mass and fat mass slope plus either vitamin A, carotene, fiber, magnesium, or phosphorus (R2 from 0.31 to 0.25) and fat mass slope plus sodium (R2 = 0.24). The significant variable in the model predicting L2-4 slope was energy intake (R2 = 0.17, P < 0.05). We conclude that nutrient intake, exercise, and body composition are related to bone mineral density rate of change and that relations among these variables vary by bone site.