Detailed insights into the formation pathway of CdS and ZnS in solution: a multi-modal in situ characterisation approach.

The high stability, high availability, and wide size-dependent bandgap energy of sulphidic semiconductor nanoparticles (NPs) render them promising for applications in optoelectronic devices and solar cells. However, the tunability of their optical properties depends on the strict control of their crystal structure and crystallisation process. Herein, we studied the structural evolution during the formation of CdS and ZnS in solution by combining in situ luminescence spectroscopy, synchrotron-based X-ray diffraction (XRD) and pair distribution function (PDF) analyses for the first time. The influence of precursor type, concentration, temperature and heating program on the product formation and on the bandgap or trap emission were investigated in detail. In summary, for CdS, single-source precursor (SSP) polyol strategies using the dichlorobis(thiourea)cadmium(II) complex and double-source precursor approaches combining Cd(CH3COO)2·2H2O and thiourea led to the straightforward product at 100 °C, while the catena((m2-acetato-O,O')-(acetate-O,O')-(m2-thiourea)-cadmium) complex was formed at 25 and 80 °C. For ZnS, the reaction between Zn(CH3COO)2·2H2O and thiourea at 100 °C led to the product formation after the crystallisation and dissolution of an unknown intermediate. At 180 °C, besides an unknown phase, the acetato-bis(thiourea)-zinc(II) complex was also detected as a reaction intermediate. The formation of such reaction intermediates, which generally remain undetected applying only ex situ characterisation approaches, reinforce the importance of in situ analysis for promoting the advance on the production of tailored semiconductor materials.

How do layered double hydroxides evolve? First in situ insights into their synthesis processes.

Despite the importance of layered double hydroxides (LDHs) in catalysis, medicine and water treatment, the crystallisation process of these materials is seldom investigated. In this study, in situ characterisation techniques granted unprecedented experimental access to the formation dynamics of carbonate-intercalated Mg2+/Al3+ LDHs as model system when applying the most relevant co-precipitation approaches by exploring the effects of temperature and concentration of reactants. For this purpose, a combinatorial multi-modal characterisation approach was applied involving in situ measurements of pH, ion conductivity and light scattering, as well as synchrotron-based in situ X-ray diffraction (XRD). Shortly after beginning the addition of basic solutions (i.e., sodium carbonate and sodium hydroxide) to the solutions of magnesium nitrate hexahydrate and aluminium nitrate nonahydrate, a stable pH was reached due to the uptake of hydroxyl ions for nuclei formation. Shortly after, crystal growth phase was detected by an increase in the light scattering signal and confirmed via in situ XRD. Increasing the concentration of reactants accelerated the onset of crystal growth by 70% without significantly changing the crystallite size. On the other hand, increasing the temperature up to 65 °C showed a smaller influence on the reaction kinetics but resulted in a two-fold increase in crystallite size. Adding the solution of metal precursors to the basic solution, saturation was rapidly reached, without an induction period, favouring the formation of very small crystallites of approximately 10 nm.

Association between pre hemodialysis serum sodium concentration and blood pressure: results from a retrospective analysis from the international monitoring dialysis outcomes (MONDO) initiative.

A recent study from the United Kingdom indicates an association between pre hemodialysis (HD) serum sodium (SNa(+)) and systolic and diastolic blood pressure (SBP and DBP) in chronic HD patients. We extend this analysis to an international cohort of incident HD patients. The Monitoring Dialysis Outcomes initiative encompasses patients from 41 countries. Over 2 years monthly pre-HD SNa(+) levels were used as predictors of pre-HD SBP and DBP in a linear mixed model (LMM) adjusted for age, gender, interdialytic weight gain, diabetes, serum albumin and calcium. Similar models were constructed with DBP as outcome. Analyses were carried out stratified by continent (North and South America; Europe and Asia). LMMs were also constructed for the entire observation period of 2 years, and separately the first and the second year after HD initiation. We studied 17 050 incident patients and found SNa(+) to have a significant slope estimate in the LMM predicting pre-HD SBP and DBP (ranging from 0.22 to 0.29 and 0.10 to 0.21 mm Hg per mEq l(-1), respectively, between the continents). The findings were similar in subsets of SBP and SNa(+) tertiles, and separately analyzed for the first and second year. Our analysis shows an independent association between SNa, SBP and DBP in a large intercontinental database, indicating that this relation is a profound biological phenomenon in incident and prevalent HD patients, generalizable to an international level and independent of SBP and DBP magnitude.

LC-MS/MS progress in newborn screening.

Newborn screening programs detect treatable disorders in infants before they become symptomatic. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has greatly increased the screening possibilities by monitoring levels of amino acids and acylcarnitines. After the initial screening step, LC-MS/MS can also be used in screening positive samples as a second tier test to differentiate between true and false positive samples. As the list of disorders screened for by LC-tandem MS increases, questions arise about screening for untreatable disorders, such as some lysosomal storage diseases (LSDs). For LSDs screening methods are being developed and tested more quickly than treatments are becoming available. This goes against one of the main tenets of newborn screening which requires that a treatment be available. LC-MS/MS can detect several disorders with a single injection, which is important in high throughput laboratories. Measuring different amino acids and acylcarnitines can be used to detect up to 45 different inherited disorders depending on how diseases are counted. The LSD assays are designed in a similar way to detect multiple disorders with common sample preparation and a single injection. The clinical implications of applying this technology to NBS on a large scale in many jurisdictions across the world are discussed.

Simple method for the quantitative analysis of endogenous folate catabolites p-aminobenzoylglutamate (pABG) and its acetamido (apABG) derivative in human serum and urine by liquid chromatography-tandem mass spectrometry.

OBJECTIVE: To develop a routine method for quantitative measurement of the folate catabolites p-aminobenzoylglutamate (pABG) and acetamidobenzoylglutamate (apABG) in serum and urine using liquid chromatography-tandem mass spectrometry (LC-MS/MS). DESIGN AND METHODS: Urine, serum and aqueous standards were thawed. Two microliters of d3-glutamic acid (d3-Glu; 1 mmol/L) was added to 200 uL of specimen as internal standard. The samples were acidified with 4 uL 6N HCL, and aliquots were precipitated with 2 volumes (412 uL) of acetonitrile. For urine specimens 30 volumes (6.18 mL) of acetonitrile was used. Samples were centrifuged at 1900 x g for 10 min and the supernatant (10 microL) injected into a Biorad CAT/MET analytical column fitted to the LC-MS/MS. Detection of the catabolites was by selective multiple ion monitoring (multiple SRM) of the respective transitions. Urine and serum samples were analysed in a group of healthy volunteers and in anonymous samples from patients being tested for PTH and urinary catecholamines. RESULTS: pABG and apABG eluted at 5.2 and 4.74 min, respectively while the d3-glutamic acid eluted at around 7 min. Limit of quantitation (LOQ) for both catabolites was 10 nmol/L (which is equivalent to 33.3 fmol for a 10 microL injection). Limit of detection (LOD) was 1 nmol/L based on a signal to noise ratio of 5:1. A linear calibration curve was obtained from 10 to 100 nmol/L for serum specimens and from 10 to 200 micromol/L for urines. Imprecision for spiked serum samples (n=10) was between 2.5 and 20% for apABG and 4.5 and 21% for pABG (at 10 and 100 nmol/L, respectively). Imprecision for spiked urine samples (n=10) was between 2.9 and 4.0% for apABG and 6.0-12.7% for pABG. Recoveries were between 80 and 122% for serum samples and between 92 and 102% for urine specimens. Total folate catabolites in random urine samples from volunteers (n=5) are 2.9+/-2.3 umol/L (mean+/-S.D.). This group also had total serum catabolites of 11.9+/-7.6 nmol/L and serum folate of 35.3+/-5.8 nmol/L. Serum from patients being tested for PTH (n=11) had serum folate levels of 27.0+/-10.4 nmol/L with total serum catabolites of 20.4+/-23.8 nmol/L. Levels of serum folate and total catabolites in pregnant women (n=18) were 33.9+/-22.7 and 11.4+/-8.7 nmol/L, respectively. Mean urinary folate catabolites in patients being tested for urinary catecholamines (n=19) was 581.8+/-368.4 nmol/L. CONCLUSION: A simple, reliable and highly specific method by LC-MS/MS for detecting and quantifying the folate catabolites pABG and apABG was developed. This enables, for the first time, the routine clinical analysis of folate utilization in patients.

Free and bound enantiomers of methadone and its metabolite, EDDP in methadone maintenance treatment: relationship to dosage?

OBJECTIVES: To determine the effects of metabolism and protein binding on the relationship between administered dose, blood levels of R methadone and biological response by measuring the free and protein-bound forms of the R and S enantiomers of methadone and EDDP, its metabolite. DESIGN AND METHODS: To measure free and total drug, trough levels were collected from 45 methadone clients. To measure free methadone, samples were filtered using ultrafiltration with a MW weight cut-off of 10,000 and extracted using liquid-liquid extraction. The solvent was evaporated and samples reconstituted in mobile phase for analysis by LC/MS/MS. Total analyte was determined by extracting unfiltered samples. Enantiomeric separation of methadone and EDDP was by chiral chromatography. RESULTS: The presence of unmetabolized methadone suggested that none of the patients were very fast metabolizers. R and S forms were metabolized at the same rate at all administered doses. Free R methadone levels correlated both with methadone dose and with the total amount of R methadone. The free fraction of R methadone (%free R) was higher at lower doses than at high doses, varied from 5 to 25% and was inversely proportional to the total dose of administered drug in a relationship that was logarithmic and non-linear. CONCLUSIONS: By measuring the free, biologically active form of the drug, we were unable to account for the large variations in dose required between different patients to prevent the onset of withdrawal symptoms. The reason for the large range in dosage may be multifactorial.

Determination of free and protein-bound methadone and its major metabolite EDDP: enantiomeric separation and quantitation by LC/MS/MS.

OBJECTIVE: To measure free and protein-bound R- and S-enantiomers of methadone and its major metabolite, 2-ethylidine-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) in serum. METHODS: To determine free fraction, samples were filtered using ultrafiltration membranes with a molecular weight cut-off of 10,000 Da and extracted using liquid-liquid extraction. The solvent extract was evaporated and reconstituted in mobile phase for analysis by LC/MS/MS. Total analyte was determined by extracting unfiltered samples. Enantiomeric separation was by chiral chromatography. RESULTS: LC conditions resulted in baseline separation of R- and S-EDDP, and 85% resolution of methadone enantiomers. Precision of spiked specimens for both R- and S-methadone and R- and S-EDDP was less than 10% at 100 nM, and did not exceed 20% at 10 nM. CONCLUSIONS: Using minimal sample clean-up and a total instrument run-time of 10 min, a rapid, sensitive and highly specific method was developed for quantitation of free and total R- and S-enantiomers of methadone and EDDP.

[Psychiatry]. / Psychiatrie.

The main innovation of the year 2004 was the introduction of a new, second-generation antipsychotic drug with a new mechanism of action (partial dopamine agonist), encouraging first clinical results, and an advantageous clinical tolerance profile. Additionally, three new galenic forms are presented: an oral, extended-release form of methylphenidate that could be useful in the treatment of attention-deficit/hyperactivity disorders; an intramuscular depot form of a second-generation antipsychotic drug (risperidone) with the advantage of improving adherence; and an intramuscular form of a second generation antipsychotic (olanzapine) that is valuable in emergency situations. Finally, we will briefly give an update on the advantages of lamotrigine in bipolar depression.

Urinary screening for methylphenidate (Ritalin) abuse: a comparison of liquid chromatography-tandem mass spectrometry, gas chromatography-mass spectrometry, and immunoassay methods.

OBJECTIVE: To develop a routine method for detecting methylphenidate (Ritalin) use among drug abusers using liquid chromatography-tandem mass spectrometry (LC/MS/MS). The new methodology was designed to replace less reliable and/or more expensive and time-consuming techniques (GC/MS and ELISA) currently employed in our laboratory, and to provide a combined one-step screening and confirmation LC/MS/MS method. DESIGN AND METHODS: Because methylphenidate abuse is very prevalent in Saskatchewan, there is a demand to provide high volume urine screening both to detect abuse, and to monitor compliance. Random urine samples sent for drugs of abuse testing, standards, and controls were diluted 1:100 in methanol. Diluted specimens were injected directly into an Agilent 1100 liquid chromatograph coupled to a Sciex API 2000 mass spectrometer. The method utilized selected reaction monitoring (SRM) as well as an electrospray ionization source (EIS) to detect both urinary methylphenidate and the more prevalent metabolite, ritalinic acid (RA). RESULTS: There appeared to be little or no sacrifice in sensitivity because the higher dilutions exhibited much less matrix effect. Limit of quantitation (LOQ) for methylphenidate was 100 nM and 500 nM for RA. Linear calibration curves from 100 to 1000 nM for Ritalin and 500 to 5000 nM for RA were acquired. Imprecision of spiked and true specimens did not exceed 10% and at the LOQ, it was less than 20%. CONCLUSIONS: A rapid, sensitive, reliable, and highly specific method by LC/MS/MS for detecting methylphenidate and its metabolite, RA, were developed. Both the cost and performance of the LC/MS/MS method were superior to GC/MS or ELISA, and it allows use of a single rapid procedure for both screening and confirmation.

[Extent of resection in surgery of stomach carcinoma]. / Resektionsausmass in der Chirurgie des Magenkarzinoms.

The extraluminal extent of resection in cases of advanced gastric cancer is controversial. If, however, following meticulous staging--including the detection of free abdominal tumor cells--complete resection seems possible, then multivisceral resection is justified. If complete resection is achieved, the prognosis of these patients can be improved. Left pancreatic resection should be performed only if the tumor invades the pancreas directly. Splenectomy is indicated if the tumor invades the organ directly or if there are locally advanced tumors of the proximal third of the stomach and tumors of the esophageal-gastric junction. However, it has to be kept in mind that splenectomy is an independent negative prognostic factor. The extent of lymphadenectomy (LA) in gastric cancer is still under discussion. According to the 10-year results of the Dutch Gastric Cancer Study, there might be subgroups which have a survival benefit after extended (D2) LA. These include, as the German Gastric Cancer Study corroborated, patients with very early stage II and stage IIIa lymph node metastases. As neither of these stages can at present be diagnosed before or during surgery, D2 lymphadenectomy should be the standard procedure for all patients with gastric cancer. Recent studies have shown that it might be possible with the help of the Sentinel Node Technique to individualize lymphadenectomy in locally gastric cancer as well. The beneficial effects of adjuvant chemoradiation in gastric cancer do not mean, however, that the extent of resection may be reduced. Adjuvant chemoradiation following complete resection and D2 lymphadenectomy should still not be regarded as standard therapy.

[Second opinion in tumor surgery. Valuable--but needing improvement]. / Die zweite Meinung in der Tumorchirurgie. Sinnvoll--aber verbesserungswürdig.

In complicated oncological cases, a second opinion is desirable, also in the view of the care-providing surgeon. It serves interdisciplinary therapeutic planning, and helps improve the quality of treatment. In the case of highly consequential interventions, the patient has a legal right to a second opinion. On a practical level, however, the implementation of this possibility encounters problems: organizational shortcomings, incomplete patient documentation, the stresses of patient transportation, loss of valuable time, in particular in the case of postal consultation, following consultation in a center the carrying out of treatment there, whether at the urging of the doctors there or the patient himself, lack of remuneration for the efforts of the consultants. Today, however, all the necessary technical facilities are in place to enable various experts to be consulted, virtually simultaneously, on any case, via video-conferencing.

Prognostic factors in gastric stump carcinoma.

OBJECTIVE: To compare prognostic results in patients with gastric stump cancer (GSC) versus those with primary gastric cancer (PGC). SUMMARY BACKGROUND DATA: Gastric stump carcinomas have often been described as having low resectability rates and a poor prognosis. METHODS: Results of surgical treatment of 50 patients with GSC were compared with that of 516 patients with PGC. RESULTS: The resectability rate was 94% for GSC patients and 96.5% for PGC patients, without significant differences in terms of postoperative complications, death rate, and median survival time (31.6 vs. 32.9 months). The multivariate analysis showed an independent prognostic effect for R0 resection, pT1 and pT2 category, and age older than 65 years. CONCLUSION: The prognosis after resection and adequate lymphadenectomy does not differ between patients with GSC and PGC.

Analysis of factors that correlate with mucositis in recipients of autologous and allogeneic stem-cell transplants.

PURPOSE: To identify predictors of oral mucositis and gastrointestinal toxicity after high-dose therapy. PATIENTS AND METHODS: Mucositis and gastrointestinal toxicity were prospectively evaluated in 202 recipients of high-dose therapy and autologous or allogeneic stem-cell rescue. Of 10 outcome variables, three were selected as end points: the peak value for the University of Nebraska Oral Assessment Score (MUCPEAK), the duration of parenteral nutritional support, and the peak daily output of diarrhea. Potential covariates included patient age, sex, diagnosis, treatment protocol, transplantation type, stem-cell source, and rate of neutrophil recovery. The three selected end points were also examined for correlation with blood infections and transplant-related mortality. RESULTS: A diagnosis of leukemia, use of total body irradiation, allogeneic transplantation, and delayed neutrophil recovery were associated with increased oral mucositis and longer parenteral nutritional support. No factors were associated with diarrhea. Also, moderate to severe oral mucositis (MUCPEAK > or = 18 on a scale of 8 to 24) was correlated with blood infections and transplant-related mortality: 60% of patients with MUCPEAK > or = 18 had positive blood cultures versus 30% of patients with MUCPEAK less than 18 (P =.001); 24% of patients with MUCPEAK > or = 8 died during the transplantation procedure versus 4% of patients with MUCPEAK less than 18 (P =.001). CONCLUSION: Gastrointestinal toxicity is a major cause of transplant-related morbidity and mortality, emphasizing the need for corrective strategies. The peak oral mucositis score and the duration of parenteral nutritional support are useful indices of gastrointestinal toxicity because these end points are correlated with clinically significant events, including blood infections and treatment-related mortality.

[Teleconsultation]. / Telekonsultation.

Teleconsultation is a consultation between two or more physicians about the diagnostic work-up and therapeutic strategy in the treatment of an individual case by means of modern telematics. Due to more complex therapeutic strategies and legally defined formal requirements, the need for teleconsultation will increase significantly in the future. Rapid technical improvements in telematics will progressively facilitate the practical performance of teleconsultation (based upon an ISDN network in the beginning, later on by the use of a national health network). The medicolegal aspects of teleconsultation have already been defined sufficiently for use in surgery. However, the question of adequate financial compensation for this type of medical service is still unclear.

[Possibilities of telecommunications in surgery]. / Möglichkeiten der Telekommunikation in der Chirurgie.

In contrast to telesurgery, telepresence involves only the audiovisual dialogue between the local surgeon and a remote expert; the latter, however, is able to actively monitor the operation by giving his judgement and recommendations. Under clinical conditions, telepresence may have the potential to facilitate intraoperative consultation of remote experts or even tele-assistance. Technical requirements consist of a suitable telemanipulation device (remotely controlled camera and indicator) and a high-duty communication system for real-time transmission of the operating site and the control signal. A minimum of 2 Mbyte/s of transmission capacity is recommended.

Structure of a 1:1 complex between L-Asp-L-Phe and L-His-Gly.

Both molecules occur in slightly folded conformations, characterized by phi 2 = -93.7 degrees in L-His-Gly and an unusual phi 2 = 60.2 degrees in L-Asp-L-Phe. The peptide linkage of L-His-Gly displays a substantial deviation from planarity with omega 1 = -163.5 degrees. The crystal packing is arranged in thick hydrophilic layers separated by hydrophobic sheets composed of L-Phe aromatic side chains. There are numerous hydrogen bonds, including an extremely short contact [O...N = 2.532 (6) A] between the ionized L-Asp and L-His side chains.

Type II pneumocyte hypertrophy without activation of surfactant biosynthesis after partial pneumonectomy.

Hypertrophic and normotrophic type II pneumocytes were isolated from pneumonectomized adult rats by unit gravity (1 g) sedimentation or by fluorescence-activated cell sorting (FACS). In vivo or in vitro, hypertrophic cells incorporated significantly more 5-bromo-2'-deoxyuridine or tritiated thymidine into acid-insoluble material than did normotrophic cells. By FACS analysis of cell subpopulations isolated by 1 g, > 97% of normotrophic cells had G0-phase DNA content. In contrast, the cell cycle distribution of hypertrophic cells was 75% G1, 5% S, and 20% G2/M phases. Rates of incorporation of tritiated choline into total cellular phosphatidylcholine (PC) were identical in type II cells isolated from normal or pneumonectomized rats. The intracellular contents of disaturated phosphatidylcholine (DSPC) and total PC, as well as the ratio of these two lipids, were the same in hypertrophic and normotrophic cells from pneumonectomized rats and in cells isolated from normal rats. No significant difference was observed in the rate at which hypertrophic or normotrophic cells incorporated choline into DSPC. These results demonstrate that type II pneumocyte hypertrophy after pneumonectomy reflects balanced cell growth secondary to cell cycle progression in vivo. The data also indicate that epithelial cell hypertrophy after pneumonectomy, in contrast to that which develops after more acute lung injury, occurs without activation of surfactant biosynthesis or storage.

Structure of L-phenylalanine L-phenylalaninium formate.

C9H11NO2.C9H12NO2+.CHO2-, M(r) = 376.41, monoclinic, P2(1), a = 11.507 (6), b = 5.638 (3), c = 14.610 (5) A, beta = 100.65 (4) degrees, V = 932 (1) A3, Z = 2, Dx = 1.342 g cm-3, lambda(Mo K alpha) = 0.7107 A, mu = 0.94 cm-1, F(000) = 400, T = 295 K, final R = 0.047 for 2693 observed reflections. The phenylalanine zwitterion and the phenylalanine cation form a Speakman-salt-type hydrogen bond [O ... O = 2.496 (3) A]. Aromatic side chains constitute a thick hydrophobic layer with edge-to-face interactions between the phenyl rings.