An oral health optimized diet can reduce gingival and periodontal inflammation in humans - a randomized controlled pilot study.

BACKGROUND: The aim of this pilot study was to investigate the effects of four weeks of an oral health optimized diet on periodontal clinical parameters in a randomized controlled trial. METHODS: The experimental group (n = 10) had to change to a diet low in carbohydrates, rich in Omega-3 fatty acids, and rich in vitamins C and D, antioxidants and fiber for four weeks. Participants of the control group (n = 5) did not change their dietary behavior. Plaque index, gingival bleeding, probing depths, and bleeding upon probing were assessed by a dentist with a pressure-sensitive periodontal probe. Measurements were performed after one and two weeks without a dietary change (baseline), followed by a two week transitional period, and finally performed weekly for four weeks. RESULTS: Despite constant plaque values in both groups, all inflammatory parameters decreased in the experimental group to approximately half that of the baseline values (GI: 1.10 ± 0.51 to 0.54 ± 0.30; BOP: 53.57 to 24.17 %; PISA: 638 mm(2) to 284 mm(2)). This reduction was significantly different compared to that of the control group. CONCLUSION: A diet low in carbohydrates, rich in Omega-3 fatty acids, rich in vitamins C and D, and rich in fibers can significantly reduce gingival and periodontal inflammation. TRIAL REGISTRATION: German Clinical Trials Register; https://www.germanctr.de (DRKS00006301). Registered on 2015-02-21.

Sensitive detection of CO2 implementing tunable thulium-doped all-fiber laser.

In this paper a compact, yet sensitive gas detection system based on a modulated, tunable thulium-doped fiber laser in the 2 µm wavelength region is reported. The laser operating wavelength range centered at a wavelength of 1.995 µm has been selected to access the R(50) transition (ν1+2ν2+ν3) of CO2 based on its line strength and to achieve isolation from interfering high-temperature water absorption features. The laser linewidth and tuning range are optimized accordingly. The modulation of the fiber laser, achieved through pump source modulation and a locking detection mechanism, has been utilized to stabilize the laser system and therefore to create a compact gas sensor with high sensitivity. The absorption spectrum, as well as the line strength and the concentration level of CO2, have been monitored through absorption spectroscopy techniques. The measured minimum detectable concentration of CO2 obtained using the system shows that it is quite capable of detecting trace gas at the ppm (parts in 10(6)) level. The stable laser performance achieved in the sensor system illustrates its potential for the development of practical, compact, yet sensitive fiber-laser-based gas sensor systems.

[Intra-operative drop in sevoflurane and oxygen concentrations. Leakage of the ventilation system]. / Intraoperativer Abfall der Sevofluran- und O2-Konzentration. Leckage des Beatmungssystems.

After problem-free induction of narcosis in an 84-year-old female patient an intra-operative drop in sevoflurane and oxygen concentrations occurred during low-flow anesthesia. Although the concentrations of sevoflurane and oxygen in the fresh gas flow were increased no adequate elevation of the inspiratory concentrations could be achieved. Disconnection of the Dräger Primus IE manual bag-valve-mask could be identified as the cause of the drop in concentrations. Interestingly no error alarm function was initiated. This case demonstrates how important knowledge of the function, set-up and alarm conditions of respiratory machines is. This should be an important component of training in anesthesiology as well as securely established algorithms for difficult ventilation to ensure safe anesthesia despite technical failures.

Bendamustine, vincristine and prednisone (BOP) versus cyclophosphamide, vincristine and prednisone (COP) in advanced indolent non-Hodgkin's lymphoma and mantle cell lymphoma: results of a randomised phase III trial (OSHO# 19).

PURPOSE: The purpose of this study was to compare the efficacy and toxicity of bendamustine, vincristine + prednisone (BOP) with a standard regimen of cyclophosphamide, vincristine + prednisone (COP) in patients with previously untreated advanced indolent non-Hodgkin's lymphoma (NHL) and mantle cell lymphoma. METHODS: A total of 164 patients with follicular lymphoma (grade 1/2), mantle cell lymphoma or lymphoplasmacytic lymphoma (immunocytoma) was randomised to treatment with vincristine 2 mg (day 1) and prednisone 100 mg/m2 (days 1-5) + bendamustine 60 mg/m2 (days 1-5) or + cyclophosphamide 400 mg/m2 (days 1-5) for a total of eight 21-day cycles. RESULTS: The rate of complete remission was 22% with BOP and 20% with COP. The projected 5-year survival rate was 61% with BOP and 46% with COP. The BOP-associated 5-year survival advantage almost reached significance in the subgroup of patients who responded to therapy (74% vs. 56%; P = 0.05), and did reach significance in responders who did not receive interferon maintenance therapy (70% vs. 47%; P = 0.03). Toxicity was acceptable in both treatment groups, although alopecia and leucopenia were more severe with COP. CONCLUSIONS: Bendamustine can efficaciously and safely replace cyclophosphamide, as used in standard COP therapy, for the treatment of patients with indolent NHL and mantle cell lymphoma. Long-term survival data suggest a clinically significant benefit for patients treated with BOP.

Sensing and responding to energetic stress: The role of the AMPK-PGC1α-NRF1 axis in control of mitochondrial biogenesis in fish.

Remodeling the muscle metabolic machinery in mammals in response to energetic challenges depends on the energy sensor AMP-activated protein kinase (AMPK) and its ability to phosphorylate PPAR γ coactivator 1 α (PGC1α), which in turn coactivates metabolic genes through direct and indirect association with DNA-binding proteins such as the nuclear respiratory factor 1 (NRF1) (Wu et al., 1999). The integrity of this axis in fish is uncertain because PGC1α i) lacks the critical Thr177 targeted by AMPK and ii) has mutations that may preclude binding NRF1. In this study we found no evidence that AMPK regulates mitochondrial gene expression through PGC1α in zebrafish and goldfish. AICAR treatment of zebrafish blastula cells increased phosphorylation of AMPK and led to changes in transcript levels of the AMPK targets mTOR and hexokinase 2. However, we saw no increases in mRNA levels for genes associated with mitochondrial biogenesis, including PGC1α, NRF1, and COX7C, a cytochrome c oxidase subunit. Further, AMPK phosphorylated mammalian peptides of PGC1α but not the corresponding region of zebrafish or goldfish in vitro. In vivo cold acclimation of goldfish caused an increase in mitochondrial enzymes, AMP and ADP levels, however AMPK phosphorylation decreased. In fish, the NRF1-PGC1α axis may be disrupted due to insertions in fish PGC1α orthologs within the region that serves as NRF1 binding domain in mammals. Immunocopurification showed that recombinant NRF1 protein binds mammalian but not fish PGC1α. Collectively, our studies suggest that fish have a disruption in the AMPK-PGC1α-NRF1 pathway due to structural differences between fish and mammalian PGC1α.

Efficacy of ifosfamide in refractory malignant diseases and uroprotection by mesna: results of a clinical phase II-study with 151 patients.

In a clinical phase II study 151 patients with refractory malignant diseases were treated with ifosfamide (60 mg/kg/day i.v. days 1-5, q 21-28 days). Altogether, 490 courses of treatment were given, 92 with conventional prophylactic measures (continuous infusion of 3-4 litre physiological saline plus alkalinization of the urine) and 398 with mesna prophylaxis (12 mg/kg i.v., 0, 4 and 8 h after administration of ifosfamide). The overall response rate (min. 25% tumor reduction) was 67/151 (44%) including four complete remissions in a fairly unfavourable patient group with testicular teratoma (39/87), soft tissue sarcoma (10/16), malignant melanoma (2/7), osteogenic sarcoma (3/6), Ewing's sarcoma (2/6), lymphoma and acute leukemia (5/7) or other histologies (6/22). The response rate in patients pretreated by cyclophosphamide containing regimen was 7/19 (36%) including one complete remission and one partial remission. Mesna was highly effective in reducing the frequency of hemorrhagic cystitis from 25/92 (27%) to 16/398 (4%) ifosfamide courses. The antitumor activity of ifosfamide in testicular cancer was not reduced by mesna. In conclusion, ifosfamide with the potent uroprotector mesna appears to compare favourably with the most active agents in the treatment of malignant diseases.

Treatment of refractory malignant lymphomas with ifosfamide/etoposide combination chemotherapy.

Twenty patients with malignant lymphomas refractory to prior combination chemotherapy were treated with ifosfamide (40 mg/kg/day i.v. days 1-5) and etoposide (120 mg/m2/day i.v., days 1, 3, 5). Altogether, 56 courses of treatment were given with prophylaxis of urinary side effects by mesna (8 mg/kg i.v. 0, 4, 8 hours after ifosfamide). The overall response rate (min. 25% tumor reduction) was 14/20 (70%) including 5/8 partial remissions in patients with non-Hodgkin's lymphoma and 2/12 partial remissions in patients with Hodgkin's disease. The lower total response rate of 7/12 in patients with Hodgkin's disease in comparison to 7/8 in patients with non-Hodgkin's lymphoma may be related to the different sensitivity of both diseases or to differences in the extent and duration of prior chemotherapy. As combination chemotherapy with ifosfamide/etoposide proved to be effective in refractory malignant lymphomas this combination may be included in combination chemotherapy programs for the salvage therapy or the initial treatment of malignant lymphomas with the alternation of non-cross-resistant chemotherapy combinations.

A new dhfrVIII trimethoprim-resistance gene, flanked by IS26, whose product is remote from other dihydrofolate reductases in parsimony analysis.

A new plasmid-borne gene, dhfrVIII, encoding high-level trimethoprim resistance (TpR) was found in an intestinal Escherichia coli. It seems to be a widely occurring mediator of TpR. Among 973 examined TpR E. coli, the new resistance gene was found in 13 (1.3%) isolates from Sweden, Finland and Nigeria. The new gene was sequenced and found to code for a dihydrofolate reductase (DHFR) of 169 amino acids (M(r) 19005). The dhfrVIII gene on the studied plasmid pLMO226 was observed to be flanked by IS26 elements. The dhfrVIII gene and a 3' unidentified open reading frame (ORF) seem to be borne on a compound transposon with IS26 at its ends, since the configuration of two IS26 flanking dhfrVIII and the unidentified ORF was conserved among the isolates that were probe-positive for the gene. Phylogeny parsimony analysis showed the dhfrVIII-encoded enzyme to be only remotely related to other known plasmid-mediated, drug-resistant DHFR. Only a few of the latter form well-supported monophyletic groups.

A single-blind study of the efficacy and safety of intravenous granisetron compared with alizapride plus dexamethasone in the prophylaxis and control of emesis in patients receiving 5-day cytostatic therapy. The Granisetron Study Group.

200 cancer patients who were due to receive fractionated chemotherapy (cisplatin greater than or equal to 15, ifosfamide greater than or equal to 1.2 or etoposide greater than or equal to 120, all mg/m2 per day) for 5 days, entered a multicentre study. Patients were randomised single-blind to receive either prophylactic intravenous granisetron (40 micrograms/kg) or alizapride (4 mg/kg followed by 4 mg/kg at 4 and 8 h post-treatment) plus dexamethasone 8 mg. Granistron was superior to the combination in preventing nausea and vomiting (54% vs. 43% complete responders). The differences were in the cisplatin-treated group. The time to first episode of moderate to severe nausea was significantly longer in the granisetron group (P = 0.03). Dosing with granisetron was more simple, with over 85% of patients requiring only a single prophylactic dose. Fewer patients receiving granisetron experienced adverse events (48% vs. 62%, P = 0.047). The frequency of constipation was, as expected, significantly higher in the granisetron group. Extrapyramidal effects, which were not noted by any granisetron patient, occurred in 5.3% of comparator patients.

A double-blind, randomised, crossover comparison of granisetron and ondansetron in 5-day fractionated chemotherapy: assessment of efficacy, safety and patient preference. The Granisetron Study Group.

We report the first double-blind, randomised, crossover study comparing granisetron and ondansetron as antiemetics in cancer chemotherapy. Patients receiving two cycles of identical chemotherapy fractionated over 5 days were given either granisetron (3 mg/day) or ondansetron (24 mg/day) on each day of chemotherapy, using a double-dummy technique to preserve study blindness. Patients then crossed over to the other therapy. 309 patients (237 male) completed the crossover: 260 received cisplatin (mean dose 19.2 mg/m2/day) and 49 received ifosfamide (mean dose 1415 mg/m2/day). Primary efficacy variables were prospectively defined as complete response (no vomiting and mild or absent nausea) over 5 days, and patient preference. Both agents achieved good control of emetic symptoms with 5-day complete response rates of 44.0% on granisetron and 39.8% on ondansetron [95% confidence interval (CI) for odds ratio 0.8, 1.9]. Complete response rates were very similar in patients receiving either cisplatin (40.8% granisetron, 37.6% ondansetron) or ifosfamide (61.2% granisetron, 51.0% ondansetron). There was a statistically significant difference in patient preference in favour of granisetron, 105 patients preferred granisetron, 79 preferred ondansetron, 121 had no preference (P = 0.048: 95% CI for odds ratio 1.00, 1.84). Single daily doses of granisetron (3 mg/day) appeared similarly effective and well tolerated to three daily doses of ondansetron (8 mg three times daily) in prevention of emesis induced by 5-day fractionated chemotherapy, however, significantly more patients preferred granisetron.

Cellular renewal kinetics of malignant non-Hodgkin's lymphomas.

Although the DNA synthesis times of the dividing NHL cell types were found to be within the normal range (7--12 h), the generation times of these neoplastic lymphocytes seem to be prolonged. However, even with a normal percentage of proliferating lymphoma cells (=growth fraction), the total number of mitotically active neoplastic lymphocytes is considerably increased in each NHL due to extensive enlargement of the total cellularity of each patient's lymphatic system. Therefore, in each NHL patient, the total cellularity of each patients' lymphatic system. Therefore, in each NHL patient, the total number of newly produced lymphoma cells is significantly increased. According to the Kiel classification of the NHL, the NHL of low-grade malignancy are considered to be characterized by the proliferative constellation of an enhanced cell production associated with reduced or normal cell death rates, whereas in the NHL of high-grade malignancy, increased cell death rates seem to be overcompensated by even higher cell renewal rates. These differences in the cellular proliferation kinetics of the NHL are supposed to be of higher prognostic and clinical significance than their B- or T-cell properties.

Kidney-derived urinary antigens assayed with monoclonal antibodies for the detection of renal damage.

For the quantitation of kidney-derived Urinary Antigens (UA) monoclonal antibodies specific for antigens localized in cells of defined subunits of the nephron were applied in sandwich ELISA. Antigen excretion was measured in the urine of healthy individuals, patients suffering from various diseases, kidney transplant recipients, and healthy volunteers receiving therapeutic doses of antibiotic drugs. In healthy individuals, in patients with diseases primarily affecting the glomerulus, and in inactive phases of chronic diseases antigen excretion was low. Toxic drug effects enhanced antigenuria. Excretion of some or all of the antigens always indicated tubular alterations. The tests thus provide information on location and extent of acute primary tubular damage.

Notable relationship between the level of tumor marker TPS in serum and survival in breast cancer.

Tissue Polypeptide Specific antigen (TPS) in serum was measured once during the follow-up of 200 breast cancer patients and compared with survival. Within 12 months, patients with normal TPS (< 80 U/L) exhibited a 3% death rate (3/96), which was undistinguishable from the mortality of normal females of corresponding age. Patients with moderate TPS (80-400 U/L) suffered 19% death (14/72), and patients with high TPS (> 400 U/L) 72% death (23/32). The relative risk (RR) of death within 6 months was 1 with normal TPS, 8 with moderate TPS, and 48 with high TPS. RR for 12 months was 1, 6, and 23, respectively. Serum TPS at admission had a significant predictive value with regard to survival up to 12 months.

Ambulatory blood pressure monitoring during pregnancy with a new, small, easily concealed monitor.

Before establishing the utility of ambulatory blood pressure monitoring during pregnancy, we evaluated the accuracy of a small, easily concealed monitor. The 59 normotensive pregnant patients were between 13 and 26 gestational weeks. For each monitor reading, two trained observers independently and simultaneously recorded blood pressures using a mercury manometer connected to the monitor cuff. Seven readings in three positions (sitting upright, semirecumbent, standing) were performed on each patient. Averaged differences between the observers' and monitor readings varied from -2.2 to -0.9 mm Hg (systolic) and from -2.8 to -0.6 (fifth-phase diastolic), indicating slight but clinically unimportant overestimation by the monitor. Correlations between averaged observers' readings and the monitor ranged from 0.79 to 0.92 (systolic) and from 0.85 to 0.92 (fifth-phase diastolic). Overall, the observers agreed with the monitor within 5 mm Hg on 94% of systolic readings and 99% of fifth-phase diastolic readings. There was no statistically significant difference in accuracy with changes in body position. We conclude that this small, quiet, noninvasive device accurately determined blood pressures during pregnancy.

Hybridization in sunfish influences the muscle metabolic phenotype.

Hybridization has the potential to exert pleiotropic effects on metabolism. Effects on mitochondrial enzymes may arise through incompatibilities in nuclear- and mitochondrial-encoded subunits of the enzyme complexes of oxidative phosphorylation. We explored the metabolic phenotype of bluegill (Lepomis macrochirus), pumpkinseed (Lepomis gibbosus), and their unidirectional F(1) hybrids (male bluegill × female pumpkinseed). In hybrids, glycolytic enzyme activities were indistinguishable from (aldolase, pyruvate kinase) or intermediate to (lactate dehydrogenase, phosphoglucoisomerase) parentals, but complex IV activities aligned with pumpkinseed, both 30% lower than bluegill. In isolated mitochondria, the specific activities of complexes I, II, and V were indistinguishable between groups. However, both complex III and IV showed indications of depressed activities in hybrid mitochondria, though no effects on mitochondrial state 3 or state 4 respiration were apparent. The patterns in complex IV activities were due to differences in enzyme content rather than enzyme V(max); immunoblots comparing complex IV content with catalytic activity were indistinguishable between groups. The sequence differences in complex IV catalytic subunits (CO1, CO2, CO3) were minor in nature; however, the mtDNA-encoded subunit of complex III (cytochrome b) showed eight differences between bluegill and pumpkinseed, several of which could have structural consequences to the multimeric enzyme, contributing to the depressed complex III catalytic activity in hybrids.

Eocene Patagonia fossils of the daisy family.

Fossil capitula and pollen grains of Asteraceae from the Eocene of Patagonia, southern Argentina, exhibit morphological features recognized today in taxa, such as Mutisioideae and Carduoideae, that are phylogenetically close to the root of the asteracean tree. This fossil supports the hypothesis of a South American origin of Asteraceae and an Eocene age of divergence and suggests that an ancestral stock of Asteraceae may have formed part of a geoflora developed in southern Gondwana before the establishment of effective dispersal barriers within this landmass.