Functional testosterone: biochemical assessment of hypogonadism in men--report from a multidisciplinary workshop hosted by the Ontario Society of Clinical Chemists.

OBJECTIVES: In 2004, the Ontario Society of Clinical Chemists (OSCC) held an invitational multidisciplinary workshop to establish the most reliable, cost-effective approach to the biochemical assessment of hypogonadism in men. METHODS: Specialists across Canada in clinical biochemistry, endocrinology, family medicine and urology were invited to participate in this workshop which included individual presentations and a consensus component addressing two challenge statements: 1) 'Determinations for total testosterone (TT) are equivalent to those for bioavailable testosterone (BAT) or calculated BAT (cBAT) or free testosterone (FT) (by analogue radioimmunoassay or equilibrium dialysis) or calculated FT (cFT)'; 2) 'There is no good evidence that borderline low testosterone concentrations in men should be treated'. The main outcomes were to identify what agreement exists in Canada, what issues were still controversial, and what research remains to be addressed. RESULTS: Six recommendations based on expert opinion addressed these main themes: investigate with morning total testosterone (TT) followed by repetition and reflexive testing of sex hormone binding globulin (SHBG) if testosterone is 8-15 nmol/L with automatic calculation of cBAT; discontinue the use of analogue free testosterone assays; and definitive methods and standards must be available to ensure standardized results. CONCLUSIONS: Total testosterone is a reliable marker for the initial investigation of men presenting with symptoms of hypogonadism; cBAT is a reasonable follow-up test in patients with equivocal biochemical or consistent symptomatic findings.

Amplitude response of single-wall carbon nanotube probes during tapping mode atomic force microscopy: Modeling and experiment.

Imaging of surfaces with carbon nanotube probes in tapping mode results frequently in complex behavior in the amplitude-distance curves monitored. Using molecular mechanics simulations, we calculate the force exerted on a nanotube pressed against a smooth surface as it undergoes deformation and buckling. This nonlinear force is then used in a macroscopic equation, describing the response of a damped harmonic oscillator, to predict the amplitude response of a nanotube AFM probe. Similarities between the prediction and experiment suggest that the complex amplitude response seen in the experiment may be explained by the nonlinearity in the force exerted on the nanotube and thus must not necessarily be related to the structure of the surface.

Electrowetting in carbon nanotubes.

We demonstrate reversible wetting and filling of open single-wall carbon nanotubes with mercury by means of electrocapillary pressure originating from the application of a potential across an individual nanotube in contact with a mercury drop. Wetting improves the conductance in both metallic and semiconducting nanotube probes by decreasing contact resistance and forming a mercury nanowire inside the nanotube. Molecular dynamics simulations corroborate the electrocapillarity-driven filling process and provide estimates for the imbibition speed and electrocapillary pressure.

Molecular-based electronically switchable tunnel junction devices.

Solid-state tunnel junction devices were fabricated from Langmuir Blodgett molecular monolayers of a bistable [2]catenane, a bistable [2]pseudorotaxane, and a single-station [2]rotaxane. All devices exhibited a (noncapacitive) hysteretic current-voltage response that switched the device between high- and low-conductivity states, although control devices exhibited no such response. Correlations between the structure and solution-phase dynamics of the molecular and supramolecular systems, the crystallographic domain structure of the monolayer film, and the room-temperature device performance characteristics are reported.

Switching devices based on interlocked molecules.

An architectural rationale and an experimental program aimed at the development of molecular electronics switching devices for memory and computing applications are discussed. Two-terminal molecular switch tunnel junctions are identified as the critical device components of molecular electronics-based circuitry. They can be tiled in two dimensions and are tolerant of manufacturing defects. Singly and multiply configurable solid-state switching devices that are based upon electrochemically switchable molecular and supramolecular systems are discussed in terms of both the synthesis of the molecular components and the fabrication and performance of the devices.

Problems identified by tutors in a hybrid problem-based learning curriculum.

Problem-based learning (PBL) tutors (n = 27) were interviewed to identify problems they encountered in facilitating a hybrid PBL-lecture curriculum. Analysis of responses yielded six problems for students: "mini-lecturing," dysfunctional group dynamics, completing cases too quickly, superficial research, frustration with tutors who lack content expertise, and lack of support for PBL. These may arise because students lack problem-solving and interpersonal skills needed to benefit from PBL.

Cardiac troponin I in patients receiving renal replacement therapy.

Current markers of myocardial injury lack specificity in patients with end-stage renal disease (ESRD). In particular, a false positive creatine kinase-MB (CKMB) elevation occurs in 5-10% of patients with ESRD. The aim of this study was to ascertain the relationship between CKMB and cardiac troponin I (cTnI), a new, highly sensitive and specific marker for myocardial injury, in the authors' dialysis population and compare their specificities. Blood samples were obtained from 112 dialysis patients (35 in peritoneal dialysis; 77 in hemodialysis). Patients were asymptomatic for cardiac ischemia and skeletal muscle injury. Mean +/- SD CKMB mass was 3.16 +/- 2.26 microg/L (range, 0.34-13.62), and cTnI was 0.025 +/- 0.061 ng/ml (range, 0.001-0.496). CKMB and cTnI levels did not correlate (r2 = 0.002; p = 0.61). CKMB mass concentration was significantly higher in men and in diabetics. No patient had a cTnI level greater than 1.5 microg/L, and eight asymptomatic patients had a CKMB mass greater than 6.7 microg/L. These data suggest a specificity of 100% for cTnI vs 94.6% for CKMB at these cutoff values. It is suggested that cTnI replace CKMB as a marker of myocardial injury in patients with ESRD.

A survey to identify potential outcome indicators for a hospital blood glucose monitoring program.

OBJECTIVE: A survey of operators of a bedside blood glucose monitoring (BGM) program at a tertiary health care institution was performed to identify potential outcome indicators for our quality assurance program. DESIGN AND METHODS: 170 surveys were randomly distributed to each nursing unit. The survey consisted of 20 questions on 4 pages. At the time of the survey, the BGM program consisted of 514 operators and 33 blood glucose meters on 17 inpatient nursing units servicing a total of 445 hospital beds. RESULTS: Seventy-eight percent of surveys were returned. Seventy-one percent of operators used the glucose meter at least once a week, 17% used it less than once a week, and 12% used it less than once a month. When asked how often they thought operators should perform BGM to ensure reliability, 65% stated "at least monthly," 8% said "bimonthly," and 27% said "3 to 4 times a year." In the previous 3 months, 59% of operators recalled "never having to repeat a BGM measurement with the glucose meter." 56% recalled "never having to confirm a BGM result by sending a venous sample to the central laboratory," 38% recalled "sending a venous sample once or twice;" 4% recalled "three or four times;" and 2% recalled "more than four times." Fifty-two percent recalled having to perform a stat analysis "less than once per month," 37% recalled "once or twice per month," and 11% recalled "once or twice per week." CONCLUSIONS: Through this survey we obtained information from our operators about the current functioning of our BGM program. Based on this information, we were able to develop a list of potential outcome indicators that we encourage health care institutions with BGM programs to consider incorporating in their quality assurance (QA) program.

How to develop an effective decentralized laboratory testing program.

In this article, we offer practical guidelines for developing an effective decentralized laboratory testing (DLT) program. Based on more than 10 years of experience with a DLT program for bedside blood glucose monitoring, we have identified eight essential steps in this process, including: developing an effective multidisciplinary DLT committee that oversees the various DLT programs; performing a needs analysis and a cost analysis as part of the application for approval of a program from the DLT committee; instrument selection and method evaluation; and, finally, implementing a DLT program including initiating a quality assurance program. A collaborative effort by everyone from the beginning is an important key to success.

Nanocrystal superlattices.

Ordered arrays, or superlattices, of metallic, insulating, or semiconducting quantum dots, represent an exciting new class of materials. These superlattices are often referred to as artificial solids, in which the nanocrystals take the place of atoms in traditional solids, and the packing arrangement of the nanocrystals determines the unit cell parameters of the superstructure. In this review, we discuss various approaches toward assembling nanocrystal superlattices and we discuss their physical properties.

Cavity ringdown laser absorption spectroscopy and time-of-flight mass spectroscopy of jet cooled platinum silicides.

The cavity ringdown technique (CRLAS) has been employed to measure the gas phase absorption spectrum of the platinum silicide molecule in the 350 nm region. All nine of the measured rovibronic bands are assigned to a single 1 sigma-1 sigma electronic transition, with a ground state vibrational frequency of omega "e = 549.0(3) cm-1, and a bond length of r"0 = 2.069(1) angstroms. The results of this study are compared with experimental data for the coinage metal silicides. Additionally, time-of-flight mass spectrometric results indicate that a variety of polyatomic metal silicides are formed in our molecular jet expansion.

Pemoline pharmacokinetics and long term therapy in children with attention deficit disorder and hyperactivity.

The pharmacokinetic behaviour of pemoline was studied in 28 children, aged 5 to 12 years, diagnosed as having the attention deficit disorder with hyperactivity. The mean elimination half-life of pemoline in these children was approximately 7 hours, which is considerably shorter than the half-life of 11 to 13 hours previously reported in adults. The tendency of the half-life to increase with age may be explained by the statistically significant decrease in total body clearance with age. The increasing half-life of pemoline with age should be considered during long term drug therapy. In this study no tolerance to the beneficial effects of pemoline was observed over 6 months. The apparent therapeutic serum concentration range for these children was attained after doses of 37.5 to 131.25 mg pemoline daily. Since the optimum serum concentration shows wide variation, the dosing regimen must be determined individually. Routine monitoring of the pemoline serum concentrations is not useful because of this apparent variation in optimum serum concentration and because of the linear relationship between dose and concentration.

Analysis of methotrexate and 7-hydroxymethotrexate by high-performance liquid chromatography and preliminary clinical studies.

The simultaneous analysis of methotrexate (MTX) and its putatively nephrotoxic metabolite, 7-hydroxymethotrexate (7OH-MTX), by high-performance liquid chromatography (HPLC) and ultraviolet spectrophotometric detection is described. Serum extraction employs SEP-PAK C-18 cartridges. Recovery ranges from 78.3 to 84.9% for MTX and 67.6 to 76.1% for 7OH-MTX. Between-day precision studies of serum (controls), containing 2.76 microM MTX and 4.40 microM 7OH-MTX, yielded coefficients of variation of 8.6 and 8.9%, respectively. Reconstitution of the dried residue in 5 mM HCl increases the retention times of 7OH-MTX and MTX, thereby enhancing their separation from extraneous serum peaks. A comparison of MTX levels determined by HPLC and a competitive protein binding assay yielded consistently lower results by HPLC. However, in comparing HPLC to EMIT, two relationships were observed: below 100 microM MTX the methods were in agreement, whereas above 100 microM MTX HPLC again provided lower values. Preliminary pharmacokinetic studies on two patients with osteogenic sarcoma are reported. After receiving 218.2 mg/kg and 148.5 mg/kg MTX in a 6-h infusion, their beta half-lives for MTX were 2.6 and 2.0 h, while their gamma half-lives were 26.2 and 42.9 h, respectively. The 7OH-MTX beta half-lives were 5.8 and 4.0 h, and the gamma half-lives were 10.2 and 15.8 h. Plasma concentration ratios of 7OH-MTX to MTX were 28.5 and 18.1 at 24 h after MTX infusion. 7OH-MTX was detected in the 15-min sample after the beginning of the MTX infusion.