Improved implantation and live delivered pregnancy rates following transfer of embryos derived from donor oocytes by single injection of leuprolide in mid-luteal phase.

PURPOSE: To determine if the use of a single injection of one-mg leuprolide acetate in mid-luteal phase can increase pregnancy rates in donor oocyte recipients. MATERIALS AND METHODS: Prospective study where couples were made aware of a study using the gonadotropin releasing hormone agonist (GnRHa) triptorelin that in the mid-luteal phase found improved pregnancy rates following embryo transfer in donor oocyte recipients. They were given the option of a single one-mg injection of the GnRHa leuprolide acetate. Pregnancy outcome was compared according to whether leuprolide was given or not. Also compared were the average first serum beta-hCG level in those who conceived according to taking leuprolide or not. RESULTS: Chi-square analysis showed a significantly higher clinical and live delivered pregnancy rate (63.9% and 52.8%) in those supplementing with leuprolide than those who did not (39.5% and 32.9%). Similarly implantation rates were significantly higher (44.2% vs. 25.2%). The average first serum beta-hCG level for those conceiving and taking leuprolide was 294 mIU/mL vs. 325 mIU/mL for those who did not. CONCLUSIONS: Similar to triptorelin the mid-luteal injection of leuprolide acetate improves pregnancy outcome in donor oocyte recipients.

Prevalence of opioid dispensings and concurrent gastrointestinal medications in Quebec.

BACKGROUND: Opioids are frequently prescribed for moderate to severe pain. A side effect of opioid usage is the inhibition of gastrointestinal (GI) motility, known as opioid-induced bowel dysfunction (OBD). OBD is typically treated prophylactically with laxatives and/or acid suppressants. AIM: The present study describes the prevalence of outpatient opioid dispensing, opioid patient demographics, and concomitant dispensing of opioids and GI medications in the Quebec Public Prescription Drug Insurance Plan in 2005. METHODS: Using a retrospective cohort design, opioid dispensings were identified using claims and reimbursement data. Laxative and acid suppressant dispensings were also identified. Concurrent use was defined as having at least one 'GI medication-exposed day' overlapping an 'opioid-exposed day'. RESULTS: More than 11% of the drug plan population was dispensed an opioid in 2005, and dispensings increased with age. Approximately two-thirds of patients who received an opioid were given codeine. Approximately one-third of opioid patients were concomitantly dispensed a GI medication, yet only 2% were dispensed a laxative. CONCLUSIONS: Although the GI side effects of opioids are well known, these side effects appear to increase with age and duration of opioid use. Opioid-related side effects, particularly OBD, should be effectively managed so as not to lead to the cessation of opioid therapy.

Frequency and severity of vasomotor symptoms among peri- and postmenopausal women in the United States.

OBJECTIVE: To describe characteristics of vasomotor symptoms, specifically daily frequency and severity, among women 40-65 years old in the United States (US). DESIGN: A survey was completed by a nationally representative sample of 4402 US women aged 40-65 years old. A questionnaire focusing on menopausal symptoms was administered online in April 2005. RESULTS: The prevalence of vasomotor symptoms was 79% in peri- and 65% in postmenopausal women. Women with daily vasomotor symptoms had an average of 2.5 very mild/mild, 2.6 moderate, 2.5 severe, and 1.4 very severe daytime hot flushes in a typical day. Women with night sweats every night had an average of 2.4 moderate, 3.2 severe, and 2.7 very severe night sweats in a typical night. Overall, 9% of peri- and 7% of postmenopausal women reported 7+ moderate to very severe vasomotor symptoms in a typical day. Although some women reported that symptoms were worse in the evening and in the summer, many women reported they were consistent, both throughout the day and throughout the seasons of the year. CONCLUSIONS: The Menopause Epidemiology Study builds upon existing literature by providing data on daily frequency and severity of vasomotor symptoms. There are many women with frequent and severe vasomotor symptoms who may benefit from treatment.

The red blood cell glucose transporter presents multiple, nucleotide-sensitive sugar exit sites.

At any instant, the human erythrocyte sugar transporter presents at least one sugar export site but multiple sugar import sites. The present study asks whether the transporter also presents more than one sugar exit site. We approached this question by analysis of binding of [3H]cytochalasin B (an export conformer ligand) to the human erythrocyte sugar transporter and by analysis of cytochalasin B modulation of human red blood cell sugar uptake. Phloretin-inhibitable cytochalasin B binding to human red blood cells, to human red blood cell integral membrane proteins, and to purified human red blood cell glucose transport protein (GluT1) displays positive cooperativity at very low cytochalasin B levels. Cooperativity between sites and K(d(app)) for cytochalasin B binding are reduced in the presence of intracellular ATP. Red cell sugar uptake at subsaturating sugar levels is inhibited by high concentrations of cytochalasin B but is stimulated by lower (<20 nM) concentrations. Increasing concentrations of the e1 ligand forskolin also first stimulate then inhibit sugar uptake. Cytochalasin D (a cytochalasin B analogue that does not interact with GluT1) is without effect on sugar transport over the same concentration range. Cytochalasin B and ATP binding are synergistic. ATP (but not AMP) enhances [3H]cytochalasin B photoincorporation into GluT1 while cytochalasin B (but not cytochalasin D) enhances [gamma-32P]azidoATP photoincorporation into GluT1. We propose that the red blood cell glucose transporter is a cooperative tetramer of GluT1 proteins in which each protein presents a translocation pathway that alternates between uptake (e2) and export (e1) states but where, at any instant, two subunits must present uptake (e2) and two subunits must present exit (e1) states.

Impact of pharmacy practices on the cost of colony-stimulating factor use in pediatric stem cell transplantation: an institution-based analysis.

PURPOSE: An evaluation of colony-stimulating factor (CSF) use in pediatric stem cell transplantation (SCT) was conducted to identify potential cost-efficiencies while preserving institutional standards of patient care. METHODS: Clinical and pharmacy records of the 55 SCTs performed during fiscal year 1995 were reviewed. Material costs per vial and per microgram, exclusive of preparation or overhead costs, were used. The best costing strategy was defined as the least expensive stocking and dispensing practice to deliver the drug actually used during the study period. RESULTS: CSFs were used in 35 of 55 transplants; 68% of usage was protocol-mandated to enhance engraftment; the remainder was associated with life-threatening complications of SCT. All use was consistent with published evidence-based guidelines. Changes in stocking and dispensing practices would result in an overall annual savings of $48,162 (fiscal year 1995 dollars), a 39% decrease in cost without a change in clinical application. CONCLUSIONS: Our analysis demonstrates that stocking and dispensing practices place significant fiscal burden in the care of pediatric-aged patients and must be carefully considered. This analysis presents a model for evaluating all components of drug cost from a global perspective, highlighting a need for examination of pharmacy and manufacturing as well as clinical practices.

An inductively coupled plasma carbon emission detector for aqueous carbohydrate separations by liquid chromatography.

An inductively coupled plasma atomic emission spectrometer is used to detect carbon-containing compounds following separation by high-performance liquid chromatography. A calcium form ligand exchange column with distilled and deionized water as the mobile phase is used to separate carbohydrates. The eluting species are detected by monitoring the carbon atomic emission line at 193.09 nm. The mass detection limits using a photomultiplier tube for sucrose and glucose are 50 ng, while that for fructose is 60 ng. The carbon emission detector should provide the same detection limit for any compound with a similar mass percent of carbon, whether or not the compound exhibits appreciable absorption characteristics. While the carbon emission detector will universally detect any organic compound, it will discriminate against species with high molar absorptivity that may be present at low concentration. Such species may act as interferences in chromatograms generated with conventional UV-visible absorption detectors. To demonstrate the utility of the carbon emission detector, three sugars (glucose, fructose, sucrose) are determined in apple, crangrape, and orange juice.

Tungsten coil devices in atomic spectrometry: absorption, fluorescence, and emission.

In this work, tungsten coil (W-Coil) devices are used as atomizers for electrothermal atomization atomic absorption spectrometry (ETAAS), electrothermal atomization laser excited atomic fluorescence spectrometry (ETA-LEAFS), and electrothermal vaporization inductively coupled plasma atomic emission spectrometry (ETV-ICP-AES). For most cases in ETAAS and ETA-LEAFS, limits of detection (LODs) using the W-Coil are within a factor of ten of those observed with commercial graphite furnace systems. LOD for Cd by W-Coil AAS is 10 pg, while LODs for As, Se, Cr, Sb and Pb by W-Coil LEAFS are 950, 320, 1400, 330, and 160 fg, respectively. The compact W-Coil device makes it an ideal atomizer for portable atomic spectrometry instrumentation, especially when coupled with a miniature charge coupled device spectrometer. Alternatively, the atomizer can be used as an inexpensive, modular add-on to an existing commercial ICP-AES system; and the thermal separation of Pb with interference elements Al, Mn, and Fe is demonstrated.

Williams syndrome and happiness.

Williams syndrome is a genetic disorder resulting in a variety of medical and developmental features, one of which is a frequent outward presentation of substantial happiness. In this paper we describe the unique expression of happiness in people with Williams syndrome, with several anecdotes and a frame by frame conversational analysis. We then discuss this happiness in the context of other dimensions of the impact of Williams syndrome, especially anxiety. We conclude with a discussion of the role of genetics in emotions.

Genetic analysis of the relationship between activation loop phosphorylation and cyclin binding in the activation of the Saccharomyces cerevisiae Cdc28p cyclin-dependent kinase.

We showed recently that a screen for mutant CDC28 with improved binding to a defective Cln2p G1 cyclin yielded a spectrum of mutations similar to those yielded by a screen for intragenic suppressors of the requirement for activation loop phosphorylation (T169E suppressors). Recombination among these mutations yielded CDC28 mutants that bypassed the G1 cyclin requirement. Here we analyze further the interrelationship between T169E suppression, interaction with defective cyclin, and G1 cyclin bypass. DNA shuffling of mutations from the various screens and recombination onto a T169E-encoding 3' end yielded CDC28 mutants with strong T169E suppression. Some of the strongest T169E suppressors could suppress the defective Cln2p G1 cyclin even while retaining T169E. The strong T169E suppressors did not exhibit bypass of the G1 cyclin requirement but did so when T169E was reverted to T. These results suggested that for these mutants, activation loop phosphorylation and cyclin binding might be alternative means of activation rather than independent requirements for activation (as with wild type). These results suggest mechanistic overlap between the conformational shift induced by cyclin binding and that induced by activation loop phosphorylation. This conclusion was supported by analysis of suppressors of a mutation in the Cdk phosphothreonine-binding pocket created by cyclin binding.

Balancing efficacy with cost: antiemetic control in the pediatric stem cell transplant (SCT) population.

We studied the practice patterns regarding intravenous (i.v.) ondansetron in children receiving stem cell transplants (SCT) at The Children's Hospital, Boston to identify cost efficiencies. The pharmacy provided information on material and preparation costs on 36 patients who received i.v. ondansetron during 41 SCT in 1995. We examined the effects of frequency, duration, and route of administration on costs. There were 498 days of ondansetron administration costing $49,083 (95$). Tremendous variation existed in frequency and duration with one third receiving i.v. ondansetron once daily, despite published evidence of equivalence of once a day and divided dosing. A switch to once daily i.v. dosing for all patients would have resulted in >/=28% savings. The median duration of use was 11 days (range 1-48); placing a cap for 7-10 days based on the length of SCT conditioning regimens, would produce savings of 48-60% over current use. By shifting administration route from i.v. to oral, a savings of 67% over current use, without a cap on duration, would be realized. Identifying areas for cost savings can be achieved after thorough analysis of all the component costs. We demonstrated that significant cost reductions could be realized by simple changes in prescribing practices without jeopardizing efficacy. These savings are achieved by standardizing dosing interval, route of administration and duration of treatment without altering daily dosage or access to an effective antiemetic. Bone Marrow Transplantation (2000) 25, 553-557.

Development of a method for the determination of ultra-trace level mercury in adipose tissue by cold vapour atomic fluorescence spectrometry.

A method for the determination of total mercury in rat adipose tissue by cold vapour atomic fluorescence spectrometry (CVAFS) has been developed. Adipose samples were initially subjected to a lyophilization procedure in order to facilitate the homogenization and accurate weighing of small tissue aliquots (approximately 50 mg). A closed vessel microwave digestion procedure using a mixture of sulphuric and nitric acids was used to liberate mercury from the adipose matrix. All mercury species were quantitatively oxidized to Hg(II) by a potassium bromate/bromide oxidation, then reduced to Hg(0) vapour by stannous chloride prior to fluorescence detection. The CVAFS exhibited a linear range of 10 pg Hg/ml to 120 pg Hg/ml. The method detection limit in solution was 2 pg Hg/ml, or 1 ng Hg/g adipose tissue, based on a nominal 50 mg sample and a final volume of 25 ml. A reference material from the National Research Council of Canada (DOLT-2, trace metals in dogfish liver) was prepared in quadruplicate in order to assess the accuracy and precision of the method. Mercury in this material was recovered at 2.22 +/- 0.08 microg/g, which is 104% of the certified level (2.14 +/- 0.10 microg/g).

Hypoglycinaemia and psychomotor delay in a child with xeroderma pigmentosum.

Glycine is a nonessential amino acid that serves as both an inhibitory and an excitatory neurotransmitter. Hyperglycinaemia occurs in non-ketotic hyperglycinaemia, a primary defect in the glycine cleavage pathway, and as a secondary feature of several inborn errors of organic acid metabolism. However, specifically low levels of glycine have never been reported. Here we report a child with complementation group C xeroderma pigmentosum (XP) characterized by a splice donor mutation in the XPC gene, multiple skin cancers and specific and persistent hypoglycinaemia. He has cognitive delay, lack of speech, autistic features, hyperactivity and hypotonia, all unexplained by the diagnosis of XP group C, a non-neurological form of the disease. Treatment with oral glycine has improved his hyperactivity. Specific hypoglycinaemia could indicate a metabolic disorder producing neurological dysfunction. Whether it is related to or coincidental with the XP is unclear.