Music enhances category fluency in healthy older adults and Alzheimer's disease patients.

Exposure to some music, in particular classical music, has been reported to produce transient increases in cognitive performance. The authors investigated the effect of listening to an excerpt of Vivaldi's Four Seasons on category fluency in healthy older adult controls and Alzheimer's disease patients. In a counterbalanced repeated-measure design, participants completed two, 1-min category fluency tasks whilst listening to an excerpt of Vivaldi and two, 1-min category fluency tasks without music. The authors report a positive effect of music on category fluency, with performance in the music condition exceeding performance without music in both the healthy older adult control participants and the Alzheimer's disease patients. In keeping with previous reports, the authors conclude that music enhances attentional processes, and that this can be demonstrated in Alzheimer's disease.

Custom cranioplasty using stereolithography and acrylic.

Numerous methods of cranioplasty have been described. Customization and prefabrication have been reported to reduce operating time and improve cosmesis. An original technique for the manufacture of customized cranioplastic implants has been developed and tested in 30 patients.Thirty patients requiring cranioplasties were selected. Data acquired from computed tomography (CT) were used to manufacture exact plastic replicas (biomodels) of craniotomy defects and master cranioplastic implants using the rapid prototyping technology of stereolithography (SL). The three-dimensional (3D) imaging techniques of mirroring and interpolation were used to extrapolate on existing anatomy to design the master implants. The master implants were hand finished to fit the defect in the corresponding cranial biomodel exactly and were then used to create a cavity mould. The mould was used to cast thermally polymerised custom acrylic implants. The surgeons reported that the customized implants reduced operating time, afforded excellent cosmesis and were cost effective. The patients reported that the opportunity to see the biomodel and implant preoperatively improved their understanding of the procedure. Two complications were noted, one infection and one implant required significant trimming. The simultaneous manufacture of the master implant (male) and biomodel (female) components from SL allowed custom accurate implants to be manufactured. Disadvantages identified were the time required for computer manipulations of the CT data (up to 2 h), difficulty in assessing the accuracy of the computer generated master as a 3D rendering, the potential for SL parts to warp, manufacturing time (minimum 2 days) and the cost of approximately $1300 US per case ($1000 for the SL biomodel and $300 for the acrylic casting).

Cerebrovascular biomodelling: a technical note.

BACKGROUND: Recently computed tomographic angiography (CTA) and MR angiography (MRA) have been used to image cerebrovascular structures. Although CTA and MRA are accurate and sensitive imaging modalities, limitations have been identified in relation to image interpretation. Stereolithographic (SL) biomodelling is a new technology that allows three-dimensional (3D) CT and MR data to be used to accurately manufacture solid plastic replicas of anatomical structures. A prospective trial of SL biomodelling in cerebrovascular surgery has been performed to investigate the feasibility and clinical utility of this new display medium. METHODS: Fifteen patients with cerebral aneurysms and 1 patient with a cerebral arteriovenous malformation (AVM) were selected. 3D CT and/or MR angiograms were acquired and 19 solid anatomical biomodels manufactured using the rapid prototyping technology of stereolithography. The biomodels were used for patient education, diagnosis, operative planning and surgical navigation. RESULTS: The biomodels replicated the CTA and MRA source data. The accuracy of one biomodel was verified by comparison with a post mortem specimen, which corresponded exactly in the x and y planes but differed by 2 mm in the z plane. The ability to closely study an overview of complex cerebrovascular anatomy from any perspective on a solid biomodel was reported to enhance the surgeon's understanding, particularly when conventional images were equivocal. Cerebrovascular biomodels were found to be useful when positioning the patient's head for surgery, for selecting the best aneurysm clip and for the simulation of clipping. Patient informed consent was anecdotally improved. Disadvantages of the technology were the cost and manufacturing time. CONCLUSIONS: Cerebrovascular biomodelling may have utility in complex cases or when the standard imaging is felt to be equivocal.

Voluntary intoxication and criminal responsibility.

This paper reviews the law related to voluntary intoxication and criminal responsibility in the 50 United States, the District of Columbia, the US Virgin islands, and Puerto Rico. Statutory and case law citations are provided which govern the use of intoxication evidence in each jurisdiction to negate mens rea (i.e., to establish diminished capacity), to support an insanity defense, and to mitigate criminal sentencing. Factors that courts typically focus on when deciding whether to admit this evidence in a particular case are discussed, and these factors are related to clinically relevant criteria.

Spinal biomodeling.

STUDY DESIGN: A prospective trial of stereolithographic biomodeling in complex spinal surgery. OBJECTIVES: To investigate the use of stereolithographic biomodeling as an aid to complex spinal surgery. SUMMARY OF BACKGROUND DATA: Of the array of imaging methods available to assist the spinal surgeon, no single method provides a complete overview of the anatomy, although three-dimensional imaging has been shown to have advantages. METHODS: Stereolithographic biomodeling is a new technology that allows data from three-dimensional computed tomographic scans to be used to generate exact plastic replicas of anatomic structures. Five patients with complex deformities were selected: two children with congenital deformities, a patient with an osteoblastoma, a patient with basilar invagination caused by osteogenesis imperfecta, and a patient with a failed lumbar fusion. Computed tomographic scanning was performed and stereolithographic biomodels generated. The stereolithographic biomodels were used for patient education, operative planning, and surgical navigation. RESULTS: The surgeons reported that biomodeling was useful in complex spinal surgery and was an effective technology. Stereolithographic biomodels were found to be particularly useful in morphologic assessment, in the planning and rehearsal of surgery, for intraoperative navigation, and for informing patients about surgical procedures. CONCLUSIONS: Stereolithographic biomodeling allows imaging data to be displayed in a physical form. This intuitive medium may improve data display and allows surgical simulation on a proxy of the surgical site. Draw-backs of the technology were a minimum 24 hours' manufacturing time and the cost.

Fetal biomodelling.

A study has been performed to determine if a stereolithographic (SL) biomodel of a fetal face could be created from 3 dimensional (3D) ultrasound (US). 3D ultrasound images were acquired by Diasonics Gateway 2D Array ultrasound systems (Diasonics Ultrasound, San Jose, CA, USA) using an electromagnetic localizer (Tomtec Free Hand Scanning Device, Tomtec Imaging Systems, Middle Cove, Australia). 3D volumetric reconstruction of the fetal face was performed and the data was prepared to guide the construction of an exact solid biomodel by stereolithography (SLA 250 3D Systems, Valencia, CA, USA). A faithful solid representation of the fetal face was produced within 12 hours of the US scan. The fetal biomodel seemed to improve the display of the 3D data. The user-friendly nature of biomodelling may have clinical utility for fetal morphological assessment and as an aid when counselling parents.

Pramlintide, a synthetic analog of human amylin, improves the metabolic profile of patients with type 2 diabetes using insulin. The Pramlintide in Type 2 Diabetes Group.

OBJECTIVE: To examine the effects of 4 weeks of subcutaneous administration of pramlintide, a synthetic analog of human amylin, on metabolic control in patients with type 2 diabetes using insulin. RESEARCH DESIGN AND METHODS: Serum fructosamine, HbA1c, and fasting plasma lipids were measured in 203 patients in a randomized double-blind placebo-controlled parallel-group multicenter trial using doses of 30 micrograms q.i.d., 60 micrograms t.i.d., and 60 micrograms q.i.d. RESULTS: Statistically significant reductions in serum fructosamine concentrations were observed in the pramlintide 30 micrograms q.i.d. group (17.5 +/- 4.9 mumol/l, P = 0.029), the pramlintide 60 micrograms t.i.d. group (24.1 +/- 4.9 mumol/l, P = 0.003), and the 60 micrograms q.i.d. group (22.6 +/- 4.1 mumol/l, P = 0.001) compared with the placebo group (3.5 +/- 3.8 mumol/l). There were also statistically significant shifts in the proportion of patients with an abnormal serum fructosamine concentration at baseline that normalized at week 4 within the pramlintide 60 micrograms t.i.d. group and the 60 micrograms q.i.d. group. Consistent with the fructosamine results, there were statistically significant reductions in HbA1c in the pramlintide 30 micrograms q.i.d. group (0.53 +/- 0.07%, P = 0.0447), the pramlintide 60 micrograms t.i.d. group (0.58 +/- 0.07%, P < 0.0217), and the pramlintide 60 micrograms q.i.d. group (0.51 +/- 0.08%, P = 0.0242) compared with the placebo group (0.27 +/- 0.08%). Total cholesterol concentrations were also statistically significantly reduced in both the pramlintide 60 micrograms t.i.d. group (8.4 mg/dl, P < 0.01) and 60 micrograms q.i.d. group (10.5 mg/dl, P < 0.01) compared with placebo (1.2 mg/dl). Body weight decreased in both of the pramlintide 60 micrograms groups, but the trend did not achieve statistical significance. The incidence of hypoglycemia was similar in all treatment groups. CONCLUSIONS: Reductions in serum fructosamine, plasma total and LDL cholesterol concentrations, and HbA1c support the hypothesis that pramlintide may improve metabolic control in patients with type 2 diabetes using insulin.

Stereolithographic (SL) biomodelling in craniofacial surgery.

BACKGROUND: Stereolithographic (SL) biomodelling allows 3D CT to be used to generate solid plastic replicas of anatomical structures (biomodels). Case reports in the literature suggest that such biomodels may have a use in craniofacial surgery but no large series or assessment of utility has been reported. A prospective trial to assess the utility of biomodelling in craniofacial surgery has been performed. METHODS: Forty patients with complex craniofacial abnormalities were selected and 3D CT scanning performed. The data of interest was used to guide a laser to selectively polymerise photosensitive resin to manufacture SL biomodels. The biomodels were used for patient education, diagnosis and operative planning. An assessment protocol was designed to test the hypothesis that biomodels in addition to standard imaging had greater utility in the surgery performed than the standard imaging alone. RESULTS: Anecdotally surgeons found biomodelling useful in 40 complex craniofacial operations. The formal assessment of the first 10 cases suggested biomodels improved operative planning (image 76%, image with biomodel 97%, P < 0.01) and diagnosis (image 82.5%, image with biomodel 99.25%, P < 0.01). Surgeons estimated that the use of biomodels had reduced operating time by a mean of 16% and were cost effective at a mean price of $1100 AUS. CONCLUSION: Biomodelling was reported as an intuitive, user-friendly technology that facilitated diagnosis, operative planning and communication between colleagues and patients. Limitations of the technology were manufacturing time and cost.

Effects of 4 weeks' administration of pramlintide, a human amylin analogue, on glycaemia control in patients with IDDM: effects on plasma glucose profiles and serum fructosamine concentrations.

The effects of 4 weeks' administration of pramlintide, an analogue of the human hormone amylin, on blood glucose control in 215 patients with insulin-dependent diabetes mellitus were examined in a 4-week, randomized, double-blind, placebo-controlled, parallel-group trial. Pramlintide was administered subcutaneously prior to meals in four dosing regimens: 30 microg four times per day (breakfast, lunch, dinner, and evening snack), 30 microg three times per day (breakfast, lunch and dinner [BLD]), 30 microg three times per day (breakfast, dinner and evening snack [BDS]), and 60 microg twice per day (breakfast and dinner). After 4 weeks of pramlintide 30 microg four times per day administration, there was a statistically significant reduction in the mean 24 h plasma glucose concentration when compared to placebo (-1.4 +/- 0.5 vs 0.3 +/- 0.5 micromol/l, p = 0.009). Serum fructosamine concentrations were reduced 62 +/- 10 micromol/l in the pramlintide 30 mg four times per day group, 43 +/- 7 micromol/l in the pramlintide 30 microg three times per day (BLD) group, 47 +/- 6 micromol/l in the pramlintide 30 microg three times per day (BDS) group, 46 +/- 7 micromol/l in the pramlintide 60 microg twice per day group, and 29 +/- 8 micromol/l by placebo. The incidence of hypoglycaemia was not different in any pramlintide group compared to the placebo group. Nausea, the most frequent adverse event, subsided after the first week of treatment in the majority of patients. In conclusion, pramlintide improved blood glucose control over a 4-week period without increased hypoglycaemia and was well tolerated. Future studies using a longer period of pramlintide administration with assessment of HbA1c as the measurement of glycaemic control are warranted.

Pramlintide: a human amylin analogue reduced postprandial plasma glucose, insulin, and C-peptide concentrations in patients with type 2 diabetes.

In order to determine the influence of a 5 h infusion of pramlintide compared to placebo on postprandial glucose, lactate, insulin, and C-peptide concentrations in patients with Type 2 diabetes, a single-blind, randomized, cross-over study was conducted in 24 patients; 12 treated with exogenous insulin and 12 managed with diet and/or oral hypoglycaemic agents. One hour after initiation of infusion, patients consumed a Sustacal test meal. The protocol was repeated on the following day with each patient receiving the alternate study medication. Pramlintide infusion in the insulin-treated patients resulted in statistically significant reductions in mean glucose, insulin, C-peptide, and lactate concentrations during the 4-h period after the Sustacal test meal. Pramlintide infusion also resulted in significant reductions of mean insulin, C-peptide, and lactate concentrations, but not glucose concentrations, in the patients treated with diet and/or oral hypoglycaemic agents. Within this latter group, reduction in postprandial glucose concentrations in individual patients correlated with glycated haemoglobin values. These results suggest that administration of pramlintide may improve glycaemic control in patients with Type 2 diabetes treated with insulin or poorly controlled on diet and/or oral hypoglycaemic agents.

Effects of pramlintide, an analog of human amylin, on plasma glucose profiles in patients with IDDM: results of a multicenter trial.

The effects of subcutaneous administration of 10, 30, or 100 microg q.i.d. pramlintide, an analog of human amylin, on plasma glucose regulation in patients with IDDM were evaluated in a multicenter trial. The plasma glucose response to a Sustacal test meal was significantly reduced compared with placebo both after 1 week and after 2 weeks of administration of 30 or 100 microg pramlintide. In addition, 24-h mean plasma glucose concentrations were significantly lowered in patients receiving 30 microg of pramlintide for 2 weeks compared with placebo, while the 100-microg pramlintide dose did not reach statistical significance for the 24-h glucose profiles. At 10 microg, pramlintide had no effect on the 24-h glucose profile or on the plasma glucose response to a Sustacal test meal. The reduction in 24-h glucose concentrations and glucose concentrations after the Sustacal test meal observed at the 30-microg pramlintide dose was not accompanied by an increased incidence of hypoglycemic events. The most frequent adverse events were dose-related and involved transient upper gastrointestinal symptoms. A majority (>80%) of the patients who reported these adverse events during week 1 did not report them in week 2. These data indicate that pramlintide effectively reduces plasma glucose concentrations as reflected in both a 24-h glucose profile and a Sustacal test meal while maintaining an acceptable safety profile.

An AIDS training program for rural mental health providers.

A total of 194 mental health care providers in Arkansas, primarily from rural areas and small communities, participated in a four-hour training program designed to improve their knowledge about the psychosocial and neuropsychiatric aspects of HIV and AIDS. Participants' responses to questionnaires completed before and after training indicated that the program was successful in achieving its goal. However, only a minimal number of providers reported completing drug, alcohol, and sexual histories and AIDS risk assessments for any of their patients before the training occurred. The authors emphasize the importance of AIDS training for rural providers.

Detection of nicotinic receptor ligands with a light addressable potentiometric sensor.

The nicotinic acetylcholine receptor, purified from Torpedo electric organ, was coupled to a light addressable potentiometric sensor (LAPS) to form a LAPS-receptor biosensor. Receptor-ligand complexes containing biotin and urease were captured on a biotinylated nitrocellulose membrane via a streptavidin bridge and detected with a silicon-based sensor. Competition between biotinylated alpha-bungarotoxin and nonbiotinylated ligands formed the basis of this assay. This biosensor detected both agonists (acetylcholine, carbamylcholine, succinylcholine, suberyldicholine, and nicotine) and competitive antagonists (d-tubocurarine, alpha-bungarotoxin, and alpha-Naja toxin) of the receptor with affinities comparable to those obtained using radioactive ligand binding assays. Consistent with agonist-induced desensitization of the receptor, the LAPS-receptor biosensor reported a time-dependent increase in affinity for the agonist carbamylcholine as expected, but not for the antagonists.

Somatic embryogenesis and plant regeneration from immature embryos of western larch.

Somatic embryogenesis was initiated from immature embryos of western larch (Larix occidentalis Nutt.) on media containing 2,4-dichlorophenoxyacetic acid and N6- benzyladenine. The effects of explant type and ammonium nitrate and glutamine concentrations on initiation were tested. Although 21-93% of explants rendered cultures in various experiments, only 3% yielded sustainable embryogenic lines. Excised embryos at the early cotyledonary stage were optimal for initiation. Maturation of somatic embryos was promoted by abscisic acid. Response to abscisic acid concentrations and duration of exposure to abscisic acid varied with genotype. Maximal results were obtained with 0.025 µ M abscisic acid for 1 to 2 weeks followed by individual culture on medium without growth regulators. Mature somatic embryos developed into shoots with roots. Plantlets have been established in peat.

Pharmacological specificity of a nicotinic acetylcholine receptor optical sensor.

The pharmacological specificity of a nicotinic acetylcholine receptor (nAChR) optical biosensor was investigated using three fluorescein isothiocyanate (FITC)-tagged neurotoxic peptides that vary in the reversibility of their receptor inhibition: alpha-bungarotoxin (alpha-BGT), alpha-Naja toxin (alpha-NT), and alpha-conotoxin (GI) (alpha-CNTX). Kinetic analysis of the time course of binding of FITC-neurotoxins to the nAChR-coated fiber gave association rate constants (k+1) of 8.4 x 10(6) M-1 min-1 for FITC-alpha-BGT, 6.0 x 10(6) M-1 min-1 for FITC-alpha-NT and 1.4 x 10(6) M-1 min-1 for FITC-alpha-CNTX. The dissociation rate constants (k-1) for the three neurotoxins were 7.9 x 10(-3) min-1. 4.8 x 10(-2) min-1 and 8.0 x 10(-1) min-1 for FITC-alpha-BGT. FITC-alpha-NT and FITC-alpha-CNTX, respectively. The equilibrium dissociation constant (Kd) values for the three toxins. calculated from these rare constants, were similar to published values obtained from tissue responses or ligand binding assays. The optical signal generated by FITC-alpha-NT binding to the nAChR-coated fiber was effectively quenched by agonists and antagonists of the nAChR but not by most of the tested agonists and antagonists of muscarinic cholinergic, adrenergic, glutamatergic, serotonergic, dopaminergic or GABAergic receptors. Interestingly, 5-hydroxy-tryptamine, haloperidol and (+)cis-methyldioxolane gave significant inhibition of FITC-alpha-NT binding to the immobilized receptor. Equilibrium constants of inhibition (Ki) for d-tubocurarine (d-TC) and carbamylcholine (carb) were determined from competition studies using FITC-alpha-CNTX. FITC-alpha-NT or FITC-alpha-BGT as probes for receptor occupancy. When the more reversible probe FITC-alpha-CNTX was used, the Ki value for d-TC was an order of magnitude lower than those determined using the less reversible probes. Ki values for carb however, were independent of the FITC-toxin probe used.

Opal phytoliths found on the teeth of the extinct ape Gigantopithecus blacki: implications for paleodietary studies.

Identification of opal phytoliths bonded to the enamel surface of the teeth of Gigantopithecus blacki indicates that this extinct ape had a varied diet of grasses and fruits. By using the scanning electron microscope at magnifications of 2000-6000x specific opal phytoliths were observed and photographed on the fossilized teeth of an extinct species. Since opal phytoliths represent the inorganic remains of once-living plant cells, their documentation on the teeth of Gigantopithecus introduces a promising technique for the determination of diet in extinct mammalian species which should find numerous applications in the field of paleoanthropology as well as vertebrate paleontology.

Biosynthetic human growth hormone in the treatment of growth hormone deficiency.

A total of 309 previously untreated children with growth hormone deficiency (GHD) (219 boys, 90 girls; mean age 8.4 +/- 3.9 years, range 1.5-19 years) were treated for up to 3 years in an ongoing trial designed to examine the long-term efficacy and safety of biosynthetic somatropin (rhGH). The children were treated with rhGH, 0.06 mg/kg (0.16 IU/kg) three times weekly. In the prepubertal children, the mean height velocity increased during the first year from 3.8 +/- 1.8 cm/year to 8.9 +/- 2.2 cm/year (n = 188). During the second and third years, their height velocities were 7.1 +/- 1.1 (n = 147) and 6.3 +/- 1.2 cm/year (n = 64), respectively. The height velocity SDS increased from -2.5 +/- 1.9 before treatment to 3.1 +/- 2.6 during the first year of treatment in the prepubertal children. The mean pretreatment height velocity in those with idiopathic GHD (3.8 +/- 1.6 cm/year) did not differ from that in children with organic GHD (3.8 +/- 2.3 cm/year). In addition, the height velocities during the first year of therapy did not differ significantly with respect to the aetiology of GHD. For the children who entered puberty during the study, the mean height velocity increased from 3.0 +/- 1.7 cm/year before treatment to 8.4 +/- 2.3 cm/year during the first year of rhGH therapy. In the first year, the height velocity of children with a bone age of less than 5 years (9.4 +/- 2.3 cm/year) was significantly greater than that in children with a bone age of 5-10 years (8.4 +/- 1.8 cm/year) or greater than 10 years (7.8 +/- 2.2 cm/year: p = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of lindane, bicyclophosphate and picrotoxin binding to the putative chloride channel sites in rat brain and Torpedo electric organ.

The relative potencies of lindane, picrotoxin and several bicyclophosphate derivatives were compared in their ability to compete with 35S-t-butylbicyclophosphorothionate (35S-TBPS) binding sites in membranes derived from Torpedo electric organ and rat brain. Lindane proved to be ten times more potent in competing with 35S-TBPS binding in electric organ than rat brain, while the bicyclophosphate analogs displayed up to three orders of magnitude greater affinity for rat brain over electric organ. GABA inhibited 35S-TBPS binding in rat brain with moderate potency (IC50 = 30 microM), while unlabelled TBPS inhibited the binding of 3H-muscimol to the GABA receptor with an IC50 greater than 100 microM. The GABA receptor antagonist bicuculline increased 35S-TBPS binding in rat brain both in the presence and absence of 30 microM GABA. The results of the study are discussed in the context of a pharmacological discrimination between voltage-sensitive and receptor-gated Cl- channels in nervous tissue, with lindane and the i-propylbicyclophosphate derivative being the most selective compounds for discriminating between them.