Proteotyping of laboratory-scale biogas plants reveals multiple steady-states in community composition.

Complex microbial communities are the functional core of anaerobic digestion processes taking place in biogas plants (BGP). So far, however, a comprehensive characterization of the microbiomes involved in methane formation is technically challenging. As an alternative, enriched communities from laboratory-scale experiments can be investigated that have a reduced number of organisms and are easier to characterize by state of the art mass spectrometric-based (MS) metaproteomic workflows. Six parallel laboratory digesters were inoculated with sludge from a full-scale BGP to study the development of enriched microbial communities under defined conditions. During the first three month of cultivation, all reactors (R1-R6) were functionally comparable regarding biogas productions (375-625 NL Lreactor volume-1 d-1), methane yields (50-60%), pH values (7.1-7.3), and volatile fatty acids (VFA, <5 mM). Nevertheless, a clear impact of the temperature (R3, R4) and ammonia (R5, R6) shifts was observed for the respective reactors. In both reactors operated under thermophilic regime, acetic and propionic acid (10-20 mM) began to accumulate. While R4 recovered quickly from acidification, the levels of VFA remained to be high in R3 resulting in low pH values of 6.5-6.9. The digesters R5 and R6 operated under the high ammonia regime (>1 gNH3 L-1) showed an increase to pH 7.5-8.0, accumulation of acetate (>10 mM), and decreasing biogas production (<125 NL Lreactor volume-1 d-1). Tandem MS (MS/MS)-based proteotyping allowed the identification of taxonomic abundances and biological processes. Although all reactors showed similar performances, proteotyping and terminal restriction fragment length polymorphisms (T-RFLP) fingerprinting revealed significant differences in the composition of individual microbial communities, indicating multiple steady-states. Furthermore, cellulolytic enzymes and cellulosomal proteins of Clostridium thermocellum were identified to be specific markers for the thermophilic reactors (R3, R4). Metaproteins found in R3 indicated hydrogenothrophic methanogenesis, whereas metaproteins of acetoclastic methanogenesis were identified in R4. This suggests not only an individual evolution of microbial communities even for the case that BGPs are started at the same initial conditions under well controlled environmental conditions, but also a high compositional variance of microbiomes under extreme conditions.

Sample prefractionation with liquid isoelectric focusing enables in depth microbial metaproteome analysis of mesophilic and thermophilic biogas plants.

Biogas production from energy crops and biodegradable waste is one of the major sources for renewable energies in Germany. Within a biogas plant (BGP) a complex microbial community converts biomass to biogas. Unfortunately, disturbances of the biogas process occur occasionally and cause economic losses of varying extent. Besides technical failures the microbial community itself is commonly assumed as a reason for process instability. To improve the performance and efficiency of BGP, a deeper knowledge of the composition and the metabolic state of the microbial community is required and biomarkers for monitoring of process deviations or even the prediction of process failures have to be identified. Previous work based on 2D-electrophoresis demonstrated that the analysis of the metaproteome is well suited to provide insights into the apparent metabolism of the microbial communities. Using SDS-PAGE with subsequent mass spectrometry, stable protein patterns were evaluated for a number of anaerobic digesters. Furthermore, it was shown that severe changes in process parameters such as acidification resulted in significant modifications of the metaproteome. Monitoring of changing protein patterns derived from anaerobic digesters, however, is still a challenge due to the high complexity of the metaproteome. In this study, different combinations of separation techniques to reduce the complexity of proteomic BGP samples were compared with respect to the subsequent identification of proteins by tandem mass spectrometry (MS/MS): (i) 1D: proteins were tryptically digested and the resulting peptides were separated by reversed phase chromatography prior to MS/MS. (ii) 2D: proteins were separated by GeLC-MS/MS according to proteins molecular weights before tryptic digestion, (iii) 3D: proteins were separated by gel-free fractionation using isoelectric focusing (IEF) conducted before GeLC-MS/MS. For this study, a comparison of two anaerobic digesters operated at mesophilic and at thermophilic conditions was conducted. The addition of further separation dimensions before protein identification increased the number of identified proteins. On the other hand additional fractionation steps increased the experimental work load and the time required for LC-MS/MS measurement. The high resolution of the 3D-approach enabled the detection of approximately 750 to 1650 proteins covering the main pathways of hydrolysis, acidogenesis, acetogenesis and methanogenesis. Methanosarcinales dominated in the mesophilic BGP, whereas Methanomicrobiales were highly abundant in the thermophilic BGP. Pathway analysis confirmed the taxonomic results and revealed that the acetoclastic methanogenesis occurred preferentially at mesophilic conditions, whereas exclusively hydrogenotrophic methanogenesis was detected in thermophilic BGP. However, for the identification of process biomarkers by comprehensive screening of BGP it will be indispensable to find a balance between the experimental efforts and analytical resolution.

Surgical denervation of the thumb CMC joint: anatomy, technique.

Surgical denervation of the thumb carpometacarpal (CMC) joint is a theoretical surgical option for thumb CMC arthritis. Some authors have described the nerve branches of thumb CMC joint. We present the innervation of the thumb CMC joint (thenar - recurrent - branch of median nerve, palmar branch of median nerve, superficial branch of radial nerve, lateral cutaneous nerve of forearm, deep branch of ulnar nerve) and the surgical techniques to achieve optimal denervation of this joint. While the results have been disappointing, this technique may be combined with conservative surgical procedures (synovectomy, ligament reconstruction) and it allows more invasive surgery in the future if necessary.

[Double trypanosomal chancre revealing West African trypanosomiasis in a Frenchman living in Gabon]. / Chancres cutanés révélant une trypanosomose africaine à Trypanosoma brucei gambiense chez un résident français au Gabon.

BACKGROUND: Human African trypanosomiasis (sleeping sickness), an endemic disease, is currently reemerging in Africa with an estimated incidence of 45,000 new cases per year. It is caused by Trypanosoma brucei subspecies and transmitted by day-biting tsetse flies. PATIENTS AND METHODS: We report a case of West African trypanosomiasis due to Trypanosoma brucei gambiense involving a Frenchman living in Libreville, Gabon. The patient presented with fever and polyadenopathies as well as two skin ulcerations highly suggestive of trypanosomiasis. Microscopic examination of cutaneous and peripheral blood smears confirmed the diagnosis of haemolymphatic infection with T. b. gambiense with trypanosomal chancres. Examination of the cerebrospinal fluid was normal. The patient was successfully treated with pentamidine isethionate. CONCLUSIONS: Recognition of cutaneous manifestations may allow a rapid diagnosis of African trypanosomiasis that is essential for timely and efficient treatment and survival.

Bilateral carpal tunnel surgery in one operation: Retrospective study.

Carpal tunnel syndrome is the most common entrapment syndrome. The incidence of a bilateral condition varies between 22% and 87%. The aim of our study was to assess the level of satisfaction and the clinical outcomes in a group of patients operated on through a bilateral neurolysis on the median nerve in the carpal tunnel, in one operating session. This is a retrospective study involving patients with an electromyographic and clinical diagnosis of bilateral carpal tunnel syndrome. Patients were treated on an outpatient basis and the bilateral neurolysis was performed by endoscopy. The postoperative data was collected during consultation by a senior surgeon or during telephone interviews. Patients were asked to respond to a satisfaction questionnaire and the functional outcome was assessed through the Quick-Disabilities of the Arm, Shoulder, and Hand (Quick-DASH) questionnaire. Twenty-nine patients with bilateral carpal tunnel syndrome were operated on in single operating sessions between January 2009 and January 2014. The average follow-up was 46 months. The average age at the time of the intervention was 45 years. Two patients were lost to follow-up, and 27 were able to be assessed. In relation to the clinical and functional outcomes, the average Quick-DASH score was 6.78 (ranges: 0-43.2). Twenty-five patients (92.5%) were satisfied with this simultaneous treatment and 26 patients (96%) would choose the same technique again. One-stage surgery in cases of bilateral carpal tunnel syndrome appears to constitute a benefit for the patient, the surgeon and the anaesthetist, but it is reserved for patients who request it and who are motivated by this type of intervention.

Sialic acid-specific affinity chromatography for the separation of erythropoietin glycoforms using serotonin as a ligand.

Recombinant human erythropoietin (rhEPO) is an important CHO cell-derived glycoprotein and the degree of sialylation of this hormone is crucial for its in vivo bioactivity. In order to improve the purification process serotonin as a potential affinity ligand was tested for preparative chromatographic separation of rhEPO glycoforms into fractions of different degrees of sialylation. Therefore, two chromatographic matrices were prepared by immobilizing serotonin on CNBr- and NHS-Sepharose™. First it was shown both matrices bind rhEPO only in its sialylated form. Results indicate that binding is pH independent between pH 3.5 to 8 suggesting it is not only based on electrostatic interactions. Second, after optimal binding conditions were identified, semi-purified rhEPO was loaded onto both matrices and eluted using a stepwise elution gradient of sodium chloride. For comparison same affinity purification experiments were performed using wheat germ agglutinin-coupled agarose, a lectin known for its affinity towards sialylated glycoproteins. To monitor changes in N-glycan fingerprint, eluate fractions were analyzed by multiplexed capillary gel electrophoresis coupled to laser-induced fluorescence (xCGE-LIF). For the serotonin matrices an increasing degree of sialylation was observed from the first to the third elution fraction while purity of rhEPO could be increased at the same time. The late elution fractions of serotonin-coupled CNBr- and NHS-Sepharose™ also showed an overall sialylation degree exceeding that of the starting material. In contrast, for rhEPO bound to wheat germ agglutinin-coupled agarose, no distinct change in the degree of sialylation could be observed after elution. Overall, these encouraging results highlight the potential of serotonin as a chromatographic ligand for the improvement of pharmaceutical purification processes of rhEPO.

Proteotyping of biogas plant microbiomes separates biogas plants according to process temperature and reactor type.

BACKGROUND: Methane yield and biogas productivity of biogas plants (BGPs) depend on microbial community structure and function, substrate supply, and general biogas process parameters. So far, however, relatively little is known about correlations between microbial community function and process parameters. To close this knowledge gap, microbial communities of 40 samples from 35 different industrial biogas plants were evaluated by a metaproteomics approach in this study. RESULTS: Liquid chromatography coupled to tandem mass spectrometry (Orbitrap Elite™ Hybrid Ion Trap-Orbitrap Mass Spectrometer) of all 40 samples as triplicate enabled the identification of 3138 different metaproteins belonging to 162 biological processes and 75 different taxonomic orders. The respective database searches were performed against UniProtKB/Swiss-Prot and seven metagenome databases. Subsequent clustering and principal component analysis of these data allowed for the identification of four main clusters associated with mesophile and thermophile process conditions, the use of upflow anaerobic sludge blanket reactors and BGP feeding with sewage sludge. Observations confirm a previous phylogenetic study of the same BGP samples that was based on 16S rRNA gene sequencing by De Vrieze et al. (Water Res 75:312-323, 2015). In particular, we identified similar microbial key players of biogas processes, namely Bacillales, Enterobacteriales, Bacteriodales, Clostridiales, Rhizobiales and Thermoanaerobacteriales as well as Methanobacteriales, Methanosarcinales and Methanococcales. For the elucidation of the main biomass degradation pathways, the most abundant 1 % of metaproteins was assigned to the KEGG map 1200 representing the central carbon metabolism. Additionally, the effect of the process parameters (i) temperature, (ii) organic loading rate (OLR), (iii) total ammonia nitrogen (TAN), and (iv) sludge retention time (SRT) on these pathways was investigated. For example, high TAN correlated with hydrogenotrophic methanogens and bacterial one-carbon metabolism, indicating syntrophic acetate oxidation. CONCLUSIONS: This is the first large-scale metaproteome study of BGPs. Proteotyping of BGPs reveals general correlations between the microbial community structure and its function with process parameters. The monitoring of changes on the level of microbial key functions or even of the microbial community represents a well-directed tool for the identification of process problems and disturbances.Graphical abstractCorrelation between the different orders and process parameter, as well as principle component analysis of all investigated biogas plants based on the identified metaproteins.

Drug delivery analysis of the Canadian multicenter trial in non-small-cell lung cancer.

PURPOSE: The Canadian multicenter trial for advanced non-small-cell lung cancer (NSCLC) reported survival benefit for chemotherapy when best supportive care was compared with vindesine-cisplatin (VP) and the combination of cyclophosphamide, doxorubicin, and cisplatin (CAP). We examined received drug delivery to document dose-intensity (DI) and total dose of drugs given to various groups in this patient population. PATIENTS AND METHODS: Plots of cumulatively received chemotherapy against time were used to evaluate drug delivery by regimen, major prognostic factors, and response status. RESULTS: Individual CAP patients show a narrow range of received DI, with the median similar to protocol. Drug delivery analysis exposed a wide range of received DI for both drugs in the more intensive VP regimen, and the median received DI was below protocol. The median received DI for cisplatin was still higher for VP than CAP, but only during the first 8 weeks of protocol treatment (20 v 10 mg/m2/wk); thereafter, the ongoing received cisplatin DI was the same (10 mg/m2/wk). The median received DI for cisplatin in each regimen was not influenced by stage, performance status, prior weight loss, sex, or response status. VP-treated patients received a higher total dose of cisplatin than CAP patients (median, 255 mg/m2 v 112.5 mg/m2; P < .0001). Median cisplatin total dose was similar for patients with a chemotherapy response or stable disease and threefold greater than for patients with progressive disease for both regimens. Although patients with chemotherapy response and stable disease had similar survival outcomes for both CAP and VP, the VP regimen had a higher proportion of patients without progressive disease (P = .004), which resulted in an overall survival advantage (P = .01). CONCLUSION: The major prognostic factors for advanced NSCLC do not exert their influence on outcome by affecting deliverable chemotherapy DI. Regimen and treatment response determined total dose. Because stable disease patients usually outnumber responding patients in advanced NSCLC trials, controlled studies should be performed that allow assessment of the impact of total received dose on outcome according to response status.

Counting the costs of chemotherapy in a National Cancer Institute of Canada randomized trial in nonsmall-cell lung cancer.

An economic evaluation was undertaken of a previously reported National Cancer Institute of Canada (NCIC) trial of chemotherapy in advanced nonsmall-cell lung cancer (NSCLC). That trial had demonstrated a survival benefit associated with the use of either vindesine and cisplatin (VP) or cyclosphosphamide, doxorubicin, and cisplatin (CAP) in relation to best supportive care (BSC). The economic technique used in this evaluation was cost-effectiveness analysis (CEA). All costs were determined from the viewpoint of two provincial health care plans. When compared with BSC, the survival benefit of 8 weeks in favor of patients receiving CAP chemotherapy was associated with an economic saving of $949.49 (in 1984 Canadian dollars). This translated into a savings of $6,171.69 per year of life gained. The mean survival benefit of 12.8 weeks that was obtained with VP chemotherapy compared with BSC was associated with an increased cost of $3,637.60 per patient, or $14,777.75 per year of life gained. The economic evaluation demonstrated that the majority of costs on each of the three treatment arms was related to hospitalization and not to the use of chemotherapy agents. These results compare favorably with estimates of cost-effectiveness (CE) of commonly used treatments for other diseases and demonstrate that a policy of supportive care is associated with costs that may exceed those of active treatment. It is concluded that economic factors should not adversely affect decisions regarding the use of chemotherapy in advanced NSCLC.

Chemotherapy can prolong survival in patients with advanced non-small-cell lung cancer--report of a Canadian multicenter randomized trial.

The survival benefit of combination chemotherapy to patients with advanced non-small-cell carcinoma of the lung (NSCLC) is controversial. To study this question, the National Cancer Institute of Canada (NCIC) Clinical Trials Group conducted a prospective randomized trial comparing best supportive care (BSC) to two chemotherapy regimens, vindesine and cisplatin (VP), and cyclophosphamide, doxorubicin, and cisplatin (CAP). Between February 1983 and January 1986, 23 centers across Canada entered 251 patients on study. Eighteen centers participated in the three-arm schema (150 patients); centers choosing not to participate in a study with a no-chemotherapy arm followed a two-arm schema comparing VP with CAP (101 additional patients). Altogether, 233 patients were eligible. Patients had measurable or evaluable disease, with either distant metastases (82.5%) or bulky limited disease considered inoperable or unsuitable for radical radiotherapy. The treatment groups were comparable in terms of age, sex, performance status, histology, disease extent, and weight loss. The overall response rates (complete response [CR] plus partial response [PR]) on the chemotherapy arms were CAP, 15.3%, and VP, 25.3% (P = .06). Patients on the three-arm portion of the trial had a median survival of 32.6 weeks when treated with VP, 24.7 weeks with CAP, and 17 weeks with BSC. The significance of the differences in survival, adjusted for prognostic factors, is as follows: chemotherapy v BSC, P = .02; VP v BSC, P = .01; and CAP v BSC, P = .05. Toxicity on the chemotherapy arms was significant, with leukopenia of severe or greater degree occurring in 37.8% (CAP) and 40.0% (VP), severe vomiting in 12.2% (CAP) and 23.3% (VP), and severe neurotoxicity in 15.6% (VP).

[Transverse radioulnar branch of the dorsal ulnar nerve: anatomic description and arthroscopic implications from 45 cadaveric dissections]. / Le rameau transverse de la branche dorsale du nerf ulnaire: anatomie et rapports avec les voies arthroscopiques du poignet: quarante-cinq dissections.

PURPOSE OF THE STUDY: We conducted an anatomic study of the transverse branch of the dorsal ulnar nerve to describe its morphology and position in relation to arthroscopic exploration portals. MATERIAL AND METHODS: Forty-five non-side-matched anatomic specimens of unknown age and gender were preserved in formol. The dorsal branch of the ulnar nerve was identified and dissected proximally to distally in order to reveal the different terminal branches. The morphometric analysis included measurement of the length and diameter of the transverse branch and measurement of wrist width. We also measured the smallest distance between the transverse branch and the ulnar styloid process, and between the branch and usual arthroscopic portals (4-5, 6R, 6U) in the axis of the forearm. RESULTS: The transverse branch was inconstant. It was found in 12 of the 45 dissection specimens (27%). In two-thirds of the specimens, the branch ran over less than 50% of the wrist width, tangentially to the radiocarpal joint. Mean nerve diameter was 1 mm. It was found 5-6 mm from the ulnar styloid process and was distal to it in 83% of the specimens. The dissections demonstrated two anatomic variants. Type A corresponded to a branch running distally to the ulnar styloid process, parallel to the joint line (10/12 specimens). Type B exhibited a trajectory proximal to the ulnar styloid process, crossing the ulnar head (2/12 specimens). The relations with the arthroscopic portals (4-5, 6R, 6U) showed that the mean distance from the branch to the portal was 3.75 mm for the 4-5 portal (distally in 11/12 specimens), 3.68 mm for the 6R portal (distally in 10/12 specimens), and 4.83 mm for the 6U portal (distally in 7 specimens and proximally in 5). DISCUSSION: To our knowledge, there has been only one report specifically devoted to this transverse branch. Two other reports simply mention its existence. According to the literature, the transverse branch of the dorsal ulnar nerve occurs in 60-80% of the cases. We found two anatomic variations different than those described in the literature. Based on our findings and data reported previously, we propose a new classification, describing two main types. In Type 1, the transverse branch arises proximally to the ulnar styloid process;type 1A and type IB are described in relation to the direction of the branch. In Type II, the branch arises distally to the ulnar styloid process;type IIA and type IIB again being described in relation to the direction of the branch. On the tangential trajectory over the radiocarpal joint, the morphometric data show a zone of risk described by a rectangle measuring 10 mm wide (6 mm distal and 4 mm proximal to the ulnar styloid process) and covering 50% of the wrist width. The relations with arthroscopic portals describe a zone of risk corresponding to a 5-7 mm radius circle centered on the portals (4-5, 6R, 6U), which includes 83% of the transverse branches.

Electroosmotic and pressure-driven flow in open and packed capillaries: velocity distributions and fluid dispersion

The flow field dynamics in open and packed segments of capillary columns has been studied by a direct motion encoding of the fluid molecules using pulsed magnetic field gradient nuclear magnetic resonance. This noninvasive method operates within a time window that allows a quantitative discrimination of electroosmotic against pressure-driven flow behavior. The inherent axial fluid flow field dispersion and characteristic length scales of either transport mode are addressed, and the results demonstrate a significant performance advantage of an electrokinetically driven mobile phase in both open-tubular and packed-bed geometries. In contrast to the parabolic velocity profile and its impact on axial dispersion characterizing laminar flow through an open cylindrical capillary, a pluglike velocity distribution of the electroosmotic flow field is revealed in capillary electrophoresis. Here, the variance of the radially averaged, axial displacement probability distributions is quantitatively explained by longitudinal molecular diffusion at the actual buffer temperature, while for Poiseuille flow, the preasymptotic regime to Taylor-Aris dispersion can be shown. Compared to creeping laminar flow through a packed bed, the increased efficiency observed in capillary electrochromatography is related to the superior characteristics of the electroosmotic flow profile over any length scale in the interstitial pore space and to the origin, spatial dimension, and hydrodynamics of the stagnant fluid on the support particles' external surface. Using the Knox equation to analyze the axial plate height data, an eddy dispersion term smaller by a factor of almost 2.5 than in capillary high-performance liquid chromatography is revealed for the electroosmotic flow field in the same column.

Concurrent weekly carboplatin and radiotherapy for nasopharyngeal carcinoma: report of a joint phase II study.

We report a phase I/II study of weekly concurrent carboplatin and radiotherapy in patients with nasopharyngeal carcinoma (M0 stage). Of 47 patients registered, 45 completed the treatment course. Twenty-six (55%) (95% CI, 41-69%) patients experienced > or =grade 3 acute toxicity (RTOG). Five (11%) (95% CI, 2-20%) patients experienced > or =grade 3 chronic toxicity. This regimen appears to have acceptable toxicity compared to the experimental arm of Phase III Intergroup Study 0099, but progression-free and overall survival are probably inferior. At present, there is no data to suggest that carboplatin can replace cisplatin for concurrent chemoradiation for NPC.

Immunochemotherapy of lung cancer.

After surgical resection of their primary lung cancer, 33 patients were randomized into one of three groups. The first received high-dose methotrexate once per month with citrovorum rescue, for 3 months. The second group were immunized monthly with a homogenate of Freund's complete adjuvant and carefully characterized soluble antigen derived from allogeneic lung cancer cells of appropriate histology, for 3 months. The third group received a combination of methotrexate and immunization monthly, for 3 months. Each patient was monitored immunologically before, during, and after the treatment period, by use of delayed hypersensitivity reactions to recall and cancer antigens, in vitro lymphocyte response to mitogens, and mixed lymphocyte blocking factor activity. The group that received methotrexate showed little change in skin reactivity, a reduction of blocking factor activity, and significant rebound overshoot in in vitro lymphocyte performance. The immunized group showed a tendency to production of blocking factor activity, striking conversion and enhancement of skin reactivity, and little change in in vitro lymphocyte performance. The immunochemotherapy group showed dramatic increases in specific skin reactivity to cancer antigens, up to 2 years after treatment, in vitro lymphocyte rebound overshoot, and reduction of blocking factor activity production. Classic life table analysis of the probability of freedom from metastases in patients with stage-I cancer indicate that the disease-free interval in patients who received methotrexate is longer than in historic and concomitant controls but not as long as in those who received immunization. The best group appear to be those who received combination immunochemotherapy. We emphasize that the small numbers in this pilot study do not yet allow firm conclusions to be made.

Improved column preparation and performance in capillary electrochromatography.

Problems encountered in capillary electrochromatography, i.e. non-reproducible column manufacture, bubble formation during usage, short column lifetimes and limited choice of packing particles are addressed by the development of fritless or single-frit, internally tapered, segmented and dead-volume free coupled capillary columns. The Van Deemter plots measured demonstrate the performance of these high-quality capillaries which are suitable for capillary electrochromatography as well as for capillary high-performance liquid chromatographic applications.

Dielectric properties of lung tissue as a function of air content.

Dielectric measurements were made on lung samples with different electrode systems in the frequency range 5 kHz-100 kHz. In the case of plate electrodes and spot electrodes, the effects of electrode polarization were partly corrected. An air filling factor F is defined, which is determined from the mass and volume of the sample. The results indicate that the electrical properties of lung tissue are highly dependent on the condition of the tissue. Furthermore they show that the conductivity sigma as well as the relative permittivity epsilon r decreases with increasing F. This is discussed using histological material. Using a simple theoretical model, the decrease of sigma and epsilon r is explained by the thinning of the alveolar walls as well as by the deformation of the epithelial cells and blood vessels through the expansion of the alveoli.

Synthesis and hypoglycemic activity of benzamidophenyl-alkanoic acid derivates: new inhibitors of gluconeogenesis.

A series of omega-[2-(N-alkylbenzamido)-phenyl]-alkanoic acids was synthesized and tested for its effects on blood glucose concentration in fasted rats and on gluconeogenesis from lactate and pyruvate in isolated perfused rat livers. The compounds led to a dose-dependent and reversible inhibition of gluconeogenesis, with 4-[2-(N-methyl-3-trifluoromethylbenzamido)-phenyl]-butanoic acid leading to a 50% inhibition at 0.02 mM. The compounds lowered blood glucose in fasted rats. No correlation between hypoglycemic effect and inhibition of gluconeogenesis could be detected, however.

An analysis of success and failure of apicoectomies.

The radiographs from 715 patient charts were analyzed to study the effect of 11 factors on the success and failure of apicoectomies. Of these, 424 had recall radiographs of 6 months or more and were evaluated for changes in radiolucencies. The data were analyzed by cross-tabulation and chi-square analysis for significant relationships. Complete healing was found in 65% of the recall cases, while incomplete and unsatisfactory healing occurred in 29.4% and 5.6% of the cases, respectively. Complete healing was found to increase with patient age. Those over 60 yr of age had the highest percentage of complete healing. No statistical difference in healing was found between maxillary and mandibular teeth. Also, postsurgical healing associated with those teeth which were inadequately obturated with gutta-percha, silver points, or paste-filling materials did not differ significantly. No significant difference in healing was found between the teeth that were retreated nonsurgically before surgery and those that were not. Healing was independent of the placement of a retrofilling as well as the type of retrofilling period. Significantly better healing was seen with teeth that were permanently restored following surgery.

Relative weights of the human carpal bones: biological and functional interests.

The relative carpal weights (Weight of each of the eight carpal bones/Weight of the complete carpus x 100) were studied in a series of 95 complete human adult carpi (dried bones). The greatest was the capitatum (19.92%; mean rank 1.16) and the smallest the pisiform (4.43%; mean rank 8.00). The scaphoideum and the hamatum presented very near values (17.19 and 15.81%; mean ranks 2.34 and 2.74), as did the lunatum and trapezium (12.56 and 12.52%; mean ranks 4.41 and 4.48), and the triquetrum and trapezoideum (9.21 and 8.36%; mean ranks 6.19 and 6.68). Within the proximal row, a regular radio-ulnar decrease was observed from the scaphoideum (39.58%) to the pisiform (10.20%). Within the distal row, a marked break existed between the trapezoideum (14.77%) and the capitatum (35.19%); the capitato-hamatal element represented 63.11% of the distal row. The distal row (mean 56.61%) was always a little heavier than the proximal row (mean 43.39%), resulting in a mean proximo-distal weight ratio of 0.77. A radio-ulnar decrease in the relative weights was observed from the radial to the ulnar carpal columns. The determination of the relative carpal weights is simple, reproducible, non-invasive, rapid, and inexpensive, and can be considered an interesting and valuable approach to the estimation of the relative carpal volumes. Relative carpal weights reveal the intrinsic proportions of the carpus and are the reflection of biological, functional and evolutionary constraints. Interesting relations appear with carpal growth and ossification, with functional characteristics, and with evolutionary processes.

Microvascularisation of the raphe buccalis in edentulous subjects, fetus, new-born and adult.

The aim of this study is to describe the microvascularisation of the raphe buccalis located at the inner surface of the cheek. The raphe buccalis is the zone where the maxillary and mandibulary prominences fuse in the embryo during the second month of life. This study was conducted using heads from edentulous subjects, fetuses, newborns and adults, injected with Indian ink in agar, then dissected or sectioned in the three basic planes. The vascular networks of the raphe buccalis are as followed: a deep reticular network, a superficial reticular network and a papillary network. The microvascularisation of the raphe buccalis classifies it as a continuation of the commissure of the mouth and of the mucosa of the cheek.