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T Smith

Publications and source records attributed to T Smith.

At least 55 records · Page 3Linked to original sources
PubMed2003

Pharmacological effects of intravenous melatonin: comparative studies with thiopental and propofol.

BACKGROUND: Possible utility of high-dose i.v. melatonin as an anaesthetic adjuvant has not been studied. This study compared its effects with thiopental and propofol. METHODS: Sprague Dawley rats were assigned to receive bolus or cumulative i.v. doses of melatonin, thiopental or propofol. Righting reflex, hindpaw withdrawal to a noxious stimulus, response to tail clamping and haemodynamic effects were assessed. RESULTS: Melatonin caused a dose-dependent increase in paw withdrawal threshold and the percent of rats displaying loss of the righting reflex. Melatonin was comparable to thiopental and propofol in terms of its rapid onset of hypnosis. The mean ED(50) values for loss of righting reflex were 5.4 (SEM 1.2), 12.5 (1.1) and 178 (1.1) mg kg(-1) for propofol, thiopental and melatonin, respectively. The percent of rats displaying loss of response to tail clamping was greater with propofol than with melatonin (P<0.05). Haemodynamic changes produced by melatonin or propofol were similar in onset and magnitude. CONCLUSIONS: I.V. melatonin can exert hypnotic effects similar to those observed with thiopental and propofol. Melatonin exhibited significant antinociceptive effects but was less effective in abolishing the response to tail clamping.

Adjuvants, Anesthesia↗
PubMed2003

AA2500 testosterone gel normalizes androgen levels in aging males with improvements in body composition and sexual function.

Testosterone replacement in hypogonadal men improves body composition, mood, and sexual functioning. In this 90-d study, we compared the pharmacokinetics and treatment effectiveness of a topical testosterone gel (AA2500) at two concentrations, 50 mg/d and 100 mg/d, to a testosterone patch and placebo gel in 406 hypogonadal men. Pharmacokinetic profiles were obtained, body composition was measured, and mood and sexual function were monitored. AA2500 treatments resulted in dose-dependent improvements in all pharmacokinetic parameters, compared with testosterone patch and placebo. Mean average concentrations at d 90 T were 13.8, 17.1, 11.9, and 7.3 nmol/liter for 50 mg/d AA2500, 100 mg/d AA2500, testosterone patch, and placebo, respectively. At d 90, the 100 mg/d AA2500 treatment improved lean body mass by 1.7 kg and percentage of body fat by 1.2% to a significantly greater degree than either control treatment. Significant improvements in spontaneous erections, sexual desire, and sexual motivation were also evidenced with the 100 mg/d AA2500 dose in comparison with placebo. Testosterone gel was well tolerated; however, the testosterone patch resulted in a high rate of application site reactions. Overall, AA2500 is an effective, well tolerated treatment for hypogonadism.

Administration, Cutaneous↗
PubMed2003

Investigation of dose reduction in neonatal radiography using specially designed phantoms and LiF:Mg,Cu,P TLDs.

Many departments still do not use recommended radiographic parameters to X-ray neonates. Direct, accurate dose measurements of individual examinations may assist a department in justifying technique modifications that provide a substantial dose reduction without a significant loss of image quality. The aim of this study was to investigate dose reduction techniques for neonates in the intensive care unit. Alterations in beam energy (kVp and filtration) and collimation were investigated using specially designed phantoms mimicking a 700 g and 2000 g neonate, and ultrasensitive LiF:Mg,Cu,P thermoluminescence dosimeters (TLDs). Differences in entrance surface dose (ESD) and dose at depth (3 cm or 5 cm) were compared for two, overlapping fields centred individually on the chest and abdomen (Technique 1) and one large chest-abdomen field (Technique 2 or babygram). The large phantom was irradiated at 54 kVp, 60 kVp and 70 kVp without additional filtration and at 66 kVp and 70 kVp with a rare-earth hafnium filter. Focus-film distance (FFD) and mAs were adjusted to maintain optical density (OD) on each radiograph. The baseline dose at 54 kVp and 100 cm FFD was (46+/-2) micro Gy. Increasing the tube potential from 54 kVp to 70 kVp without additional filtration reduced the ESD by 27%. However, the addition of a 0.05 mm hafnium filter at 66 kVp further reduced the radiation dose by 13%, to produce an ESD of (28+/-2) micro Gy. All contrast details were observable at 66 kVp with hafnium filtration. Technique 1 may lead to an increase in effective dose due to field overlap, which diverges at depth, and increased scatter at the periphery of the fields.

Critical Care↗
PubMed2003

Intracellular Staphylococcus aureus. A mechanism for the indolence of osteomyelitis.

Staphylococcus aureus is the bacterial pathogen which is responsible for approximately 80% of all cases of human osteomyelitis. It can invade and remain within osteoblasts. The fate of intracellular Staph. aureus after the death of the osteoblast has not been documented. We exposed human osteoblasts to Staph. aureus. After infection, the osteoblasts were either lysed with Triton X-100 or trypsinised. The bacteria released from both the trypsinised and lysed osteoblasts were cultured and counted. Colonies of the recovered bacteria were then introduced to additional cultures of human osteoblasts. The number of intracellular Staph. aureus recovered from the two techniques was equivalent. Staph. aureus recovered from time zero and 24 hours after infection, followed by lysis/trypsinisation, were capable of invading a second culture of human osteoblasts. Our findings indicate that dead or dying osteoblasts are capable of releasing viable Staph. aureus and that Staph. aureus released from dying or dead osteoblasts is capable of reinfecting human osteoblasts in culture.

Cell Death↗
PubMed2002

Extremely low vertical-emittance beam in the accelerator test facility at KEK.

Electron beams with the lowest, normalized transverse emittance recorded so far were produced and confirmed in single-bunch-mode operation of the Accelerator Test Facility at KEK. We established a tuning method of the damping ring which achieves a small vertical dispersion and small x-y orbit coupling. The vertical emittance was less than 1% of the horizontal emittance. At the zero-intensity limit, the vertical normalized emittance was less than 2.8 x 10(-8) rad m at beam energy 1.3 GeV. At high intensity, strong effects of intrabeam scattering were observed, which had been expected in view of the extremely high particle density due to the small transverse emittance.

Journal Article↗
PubMed2002

Farm residence and exposures and the risk of allergic diseases in New Zealand children.

BACKGROUND: Studies in Europe have reported a reduced prevalence of allergy in farmers' children. We aimed to determine if there is a similar reduction in allergy among New Zealand farm children. METHODS: Two hundred and ninety-three children participated (60%) aged 7-10 years, from selected schools in small towns and the surrounding rural area. Skin prick tests (SPT) to eight common allergens were performed. Parents completed questionnaires about allergic and infectious diseases, place of residence, exposure to animals, and diet, and they provided dust from the living-room floor. Endotoxin was measured using an Limulus amoebocyte lysate (LAL) assay and Der p 1 using enzyme-linked immunoassay (ELISA). RESULTS: Current farm abode was found to increase the risk of having symptoms associated with allergy, but not SPT positivity. Independent inverse associations were found for early-life exposures: at least weekly consumption of yoghurt with hayfever (odds ratio (OR) = 0.3, 95% confidence intervals (CI) 0.1-0.7) and allergic rhinitis (OR = 0.3, 95% CI 0.2-0.7); any unpasteurized milk consumption with atopic eczema/dermatitis syndrome (AEDS) (OR = 0.2, 95% CI 0.1-0.8); cats inside or outside with hayfever (OR = 0.4, 95% CI 0.1-1.0) and AEDS (OR = 0.4, 95% CI 0.2-0.8); dogs inside or outside with asthma (OR = 0.4, 95% CI 0.2-0.8); and pigs with SPT positivity (OR = 0.2, 95% CI 0.1-0.9). CONCLUSIONS: Despite finding a protective effect of early-life animal exposures, we found a greater prevalence of allergic disease on farms.

Agriculture↗
PubMed2002

A preliminary report on the implication of RT-PCR detection of DAZ, RBMY1, USP9Y and Protamine-2 mRNA in testicular biopsy samples from azoospermic men.

In this study, reverse transcription-polymerase chain reaction (RT-PCR) was optimized to analyse the presence of DAZ, RBMY1, USP9Y, protamine-2, SRY and actin messenger RNA (mRNA) in testicular cells of men suffering from idiopathic azoospermia. All samples (n=28), including five controls, showed normal expression of actin, SRY and USP9Y. Sperm was not recovered from eight patients after testicular biopsy. Of these, four patients showed altered mRNA levels for the fertility genes, DAZ, RBMY1 and protamine-2. One patient, who was previously shown to be azoospermia factor region (AZF)b deleted, lacked RBM mRNA and presented with reduced amplification of protamine-2 mRNA. This correlated with previous studies, which proposed that RBM expression is exclusive to AZFb and that the lack of testicular RBMY1 mRNA results in suppressed spermatogenesis. Two patients were each lacking DAZ mRNA but did show expression of RBMY1 mRNA at a reduced level, suggesting that there might be residual spermatogenesis in the absence of DAZ expression. Protamine-2 mRNA was detected in one patient and was absent in the second patient. Finally, one patient lacked DAZ, RBMY1 and protamine-2 mRNA. The 19 remaining azoospermic patients presented with normal expression patterns for each of the fertility genes studied. This study demonstrates that the expression of spermatogenesis-specific genes varies in azoospermia. The study of the expression of such genes in a larger number of patients might be useful in characterizing and identifying subpopulations of azoospermic men.

Biopsy↗
PubMed2002

Molecular epidemiology of Plasmodium falciparum infections among asymptomatic inhabitants of a holoendemic malarious area in northern Ghana.

Age dependence of malaria infection was assessed in an age-stratified cluster sample of 308 individuals from Kassena-Nankana District of northern Ghana during June and July 2000. Overall prevalence of Plasmodium falciparum by microscopy was 70%, with the maximum among 5-9 year olds. Parasite density was highest (geometric mean 1922/microl blood) in 1-2 year olds. Eighty-two per cent of samples were positive by polymerase chain reaction (PCR), and restriction fragment length polymorphism typing of the P. falciparum msp2 revealed a mean msp2 multiplicity of 3.4 (range: 1-8) genotypes per PCR positive sample. Multiplicity increased with age until 5-9 years and then started to reduce again into adulthood. About 49.3% of infections belonged to the msp2 FC27 allelic family and 50.7% to the 3D7 family. On the day of the survey, only 3.6% of the participants had fever (axillary temperature >or= 37.5 degrees C) and 2.3% had fever associated with parasitaemia. The correlation between parasite density and msp2 multiplicity was 0.42; highest among infants, and decreased with age to a minimum among 5-9 year olds. Contrasting with results from Tanzania, this correlation increased with age in adolescents and adults. Parasite multiplicity is very high in this community, and the patterns of age dependence are similar to those in other holoendemic sites in Africa, validating the use of the age-multiplicity relationship as an indicator of malaria endemicity.

Adolescent↗
PubMed2002

Effect of betamethasone on maternal glucose.

OBJECTIVE: To determine the effect of single and multiple betamethasone courses on maternal fasting and postprandial glucose values. STUDY DESIGN: A prospective cohort study was performed in women receiving betamethasone at 24-34 weeks' gestation. Fasting and 1-h postprandial capillary glucose values were obtained daily following betamethasone therapy for hospitalized patients. A control group comprised outpatients who underwent weekly fasting and postprandial assessments for 3 weeks. Fasting and 1-h postprandial capillary glucose values were compared between control and betamethasone patients using an unpaired t test. RESULTS: Thirty-five women received a single course of therapy, 19 received multiple courses and 28 served as controls. Mean fasting glucose values for control patients fell within a narrow range of 81.6 +/- 10.3 to 82.2 +/- 6.4 mg/dl for weeks 1-3. Of women receiving betamethasone, 59% of fasting glucose values were greater than 90 mg/dl as compared to 16% of control fasting values (p < 0.00 1, chi2 test). Mean 1-h postprandial values for control women ranged from 107.7 +/- 15.1 to 112.3 +/- 20.0 mg/dl for weeks 1-3. Mean 1-h postprandial glucose values were < or = 140 mg/dl following one, two or three courses of betamethasone therapy. CONCLUSIONS: Betamethasone resulted in an acute increase in fasting glucose following a single course of betamethasone, whereas two or more courses of therapy resulted in a continuous elevation of fasting glucose values. One-hour postprandial values were not clinically abnormal.

Adult↗
PubMed2002

Primary cutaneous non-Hodgkin's lymphoma with aggressive histology: inferior outcome is associated with peripheral T-cell type and elevated lactate dehydrogenase, but not extent of cutaneous involvement.

BACKGROUND: The aim of this study was to explore the association between extent of cutaneous involvement, presenting features and progression-free survival (PFS) in patients with primary cutaneous non-Hodgkin's lymphoma (PCNHL) of aggressive histology. METHODS: Previously untreated patients with localized or extensive PCNHL of aggressive histology, treated with combination chemotherapy, but excluding lymphoblastic lymphoma and mycosis fungoides and its variants, were reviewed retrospectively. RESULTS: We identified 53 patients, of whom 52 (35 males, 17 females) were treated with doxorubicin-based regimens. Median age was 52 years (range 25-81 years), and disease was localized and extensive in 37 and 16 patients, respectively. Twenty-four patients had diffuse large B-cell lymphoma, nine had grade 3 follicular lymphoma, 13 had peripheral T-cell lymphoma (PTCL; not otherwise specified) and seven had anaplastic large cell lymphoma (WHO classification). With a median follow-up of 101 months (range 2-237 months) for survivors, the 10-year PFS was 65 +/- 7% and overall survival was 72 +/- 8%. The first failure involved the skin in 33% of B-cell and 91% of relapsing T-cell lymphomas. Univariate analysis revealed that PTCL (P = 0.005), lymphopenia (P = 0.01) and high serum levels of beta(2)-microglobulin (P = 0.0006) and LDH (P = 0.002), but not extent of skin involvement, were associated with inferior PFS. Multivariate analysis revealed that only PTCL and high serum lactate dehydrogenase (LDH) were independently associated with inferior PFS. CONCLUSIONS: PTCL and elevated serum LDH level, but not extent of cutaneous involvement are associated with inferior PFS in aggressive PCNHL treated with combination chemotherapy.

Adult↗
PubMed2002

Effect of helmet wear on the incidence of head/face and cervical spine injuries in young skiers and snowboarders.

PURPOSE: To evaluate whether helmets increase the incidence and/or severity of cervical spine injury; decrease the incidence of head injury; and/or increase the incidence of collisions (as a reflection of adverse effects on peripheral vision and/or auditory acuity) among young skiers and snowboarders. METHODS: During one ski season (1998-99) at a world class ski resort, all young skiers and snowboarders (<13 years of age) presenting with head, face, or neck injury to the one central medical facility at the base of the mountain were identified. On presentation to the clinic, subjects or their parents completed a questionnaire reviewing their use of helmets and circumstances surrounding the injury event. Physicians documented the site and severity of injury, investigations, and disposition of each patient. Concurrently, counts were made at the entry to the ski area of the number of skiers and snowboarders wearing helmets. RESULTS: Seventy children were evaluated at the clinic following ski/snowboard related head, neck, and face injuries. Fourteen did not require investigation or treatment. Of the remaining 56, 17 (30%) were wearing helmets and 39 (70%) were not. No serious neck injury occurred in either group. Using helmet-use data from the hill, among those under 13 years of age, failure to wear a helmet increased the risk of head, neck, or face injury (relative risk (RR) 2.24, 95% confidence interval (CI) 1.23 to 4.12). When corrected for activity, RR was 1.77 and 95% CI 0.98 to 3.19. There was no significant difference in the odds ratio for collisions. The two groups may have been different in terms of various relevant characteristics not evaluated. No separate analysis of catastrophic injuries was possible. CONCLUSION: This study suggests that, in skiers and snowboarders under 13 years of age, helmet use does not increase the incidence of cervical spine injury and does reduce the incidence of head injury requiring investigation and/or treatment.

Adolescent↗
PubMed2002

Pharmacokinetics of fluvastatin in subjects with renal impairment and nephrotic syndrome.

The pharmacokinetics (PK) and safety of fluvastatin, a hydroxymethylglutaryl-coenzyme A reductase inhibitor, were assessed in subjects with renal impairment and nephrotic syndrome. In a single-center, open-label, parallel-group study, a single dose of fluvastatin 40 mg was administered to subjects (8 per group, n = 48) with nephrotic syndrome (group II), healthy subjects (group I), and subjects with various degrees of renal impairment (groups III to VI). Subjects undergoing hemodialysis received two doses, one 2 days before and one just prior to hemodialysis. Blood samples to determine the PK parameters of fluvastatin were collected from 0 to 12 hours after drug intake. Noncompartmental PK evaluation and statistical analysis (descriptive and ANOVA) were performed. Safety was evaluated and vital signs were monitored. There was no difference in the PK parameters AUC0-infinity and Cmax of fluvastatin between healthy subjects and subjects with renal impairment. Fluvastatin was not removed from plasma by hemodialysis. In patients with nephrotic syndrome, the values for AUC0-infinity and Cmax were less than half of those obtained in the other groups; terminal half-life values, however, were comparable. Fluvastatin was well tolerated in all study participants. Only few adverse events of mild to moderate intensity were reported. There were no clinically relevant changes in laboratory parameters in the subjects with renal impairment. Renal impairment did not affect the PK of fluvastatin after a single oral dose. Exposure to fluvastatin was lower in subjects with nephrotic syndrome. Fluvastatin also was well tolerated in subjects with nephrotic syndrome.

Adult↗
PubMed2002

Magnetic bead purification of labeled DNA fragments for high-throughput capillary electrophoresis sequencing.

We have developed an automated purification method for dye-terminator-based DNA sequencing products using a magnetic bead approach. This 384-well protocol generates sequence fragments that are essentially free of template DNA, salt, and excess dye-terminator products. In comparison with traditional ethanol precipitation protocols, this method uses no centrifugation, is rapid, completely automated, and increases the phred-20 read length by an average of 40 bases. To date, we have processed over 4 million samples with 94% averaging 641 phred-20 bases on the MegaBACE 1000 and 4000 and the ABI PRISM 3700 capillary instruments.

DNA↗
PubMed2002

Real-time polymerase chain reaction detection of bovine DNA in meat and bone meal samples.

We describe a real-time polymerase chain reaction (PCR) assay for the detection of bovine DNA extracted from meat and bone meal (MBM) samples. PCR primers were used to amplify a 271-bp region of the mitochondrial ATPase 8-ATPase 6 gene, and a fluorogenic probe (BOV1) labeled with a 5' FAM reporter and a 3' TAMRA quencher was designed to specifically detect bovine PCR product. The specificity of the BOV1 probe for the detection of the bovine PCR product was confirmed by Southern blot hybridization analysis of the probe with PCR products generated from ovine, porcine, and bovine genomic DNA extracted from blood and with PCR products generated from genomic DNA extracted from single-species laboratory scale rendered MBM samples. The specificity of the BOV1 probe was also evaluated in real-time PCR reactions including these genomic targets. Both methods demonstrated that the BOV1 probe was specific for the detection of bovine PCR product. The BOV1 probe had a detection limit of 0.0001% bovine material by Southern blot DNA probe hybridization analysis and a detection limit of 0.001% bovine material in the real-time PCR assay. Application of the real-time PCR assay to six industrial samples that had previously tested positive for the presence of bovine material with a conventional PCR assay yielded positive results with the real-time PCR assay for four samples.

Animal Feed↗
PubMed2002

Effects of hormone replacement therapy on olfactory sensitivity: cross-sectional and longitudinal studies.

OBJECTIVE: To determine whether hormone replacement therapy (HRT) preserved or improved olfactory sensitivity in healthy postmenopausal women. METHODS: Sixty-two postmenopausal women participated in a cross-sectional study of olfactory sensitivity involving detection, intensity discrimination, quality discrimination and two measures of quality recognition. In addition, 24 postmenopausal women participated in a longitudinal study of olfactory sensitivity. This study allowed for the measurement of estrogen effects (while holding practice effects constant) and the measurement of practice effects (while holding HRT conditions constant). RESULTS: In the cross-sectional study, we were unable to detect any differences between those receiving HRT and those not receiving HRT. Duration of exposure to HRT was examined by selecting women who had 5 or more years of exposure to their HRT regimen. Even after the data were reorganized into those for opposed- and unopposed-estrogen use, we were unable to detect any differences. However, olfactory threshold increased as a function of increasing age, regardless of HRT status. A gradual decrease in ability to detect odors was observed from the 4th to the 6th decade, with a greater decrease between the 6th and 7th decades. In the longitudinal study, no effects of HRT were detected even when practice effects were uncontrolled. Practice effects were assessed both between and within subjects. No effects of practice were detected when initial baseline performance was used as a covariate. CONCLUSION: Although prophylactic HRT has been suggested to be associated with improved olfactory function, we find that its use in healthy postmenopausal women does not enhance performance in a wide range of olfactory tasks.

1-Butanol↗
PubMed2001

Response to therapy is independently associated with survival prolongation in chronic myelogenous leukemia in the blastic phase.

BACKGROUND: Achievement of minimal tumor burden, such as complete response, has been accepted as a surrogate marker for improved survival in many solid and hematologic carcinomas. Several new agents have been approved recently for orphan disease indications or unmet medical needs, based on response analyses. This has not been the case for chronic myelogenous leukemia in the blastic phase (CML-BP), despite its poor prognosis, because response has not been proven to be a valuable endpoint for survival prolongation. The purpose of this study was to analyze the effect of response in CML-BP on survival prolongation. STUDY GROUP AND METHODS In total, 328 patients with CML-BP referred from 1989 to 1999 were studied; 311 patients received therapy for CML-BP, and 275 were evaluable for response. Blastic phase CML was defined by the presence of 30% or more blasts in the blood or bone marrow, or extramedullary disease. Treatment responses were reviewed and categorized as proposed in previous large studies. Four categoric response groups were defined further based on significant differences in outcome: cytogenetic response, hematologic response, bone marrow improvement, and failure. The association of treatment response with survival was evaluated by multivariate and landmark analyses. RESULTS: The association of response with survival was analyzed among the 275 patients who had evaluable responses, and follow-up information was documented. Univariate analysis of pretreatment characteristics found performance status, hemoglobin levels, platelet counts, peripheral blasts, additional chromosomal abnormalities, and blastic phase morphology as showing significant associations with survival (P < 0.1). A multivariate analysis found platelet counts and blastic morphology as independent significant factors associated with survival (P < 0.05). A landmark analysis conducted at 8 weeks from start of therapy showed the beneficial effect of achieving response on survival prolongation (P < 0.001). A repeat multivariate at the 8-week landmark time in the 240 patients alive at that time, which included pretreatment characteristics and treatment response, confirmed the independent significant association of morphology (P = 0.003), platelet counts (P = 0.04), and response (P < 0.001) with survival. CONCLUSIONS: Response to therapy is a significant independent factor associated with survival prolongation and maybe an acceptable therapeutic endpoint for approving new treatments in CML-BP.

Adolescent↗