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Biomedical subjects

G Cunningham

Publications and source records attributed to G Cunningham.

At least 19 recordsLinked to original sources
PubMed2002

L-H transition in the mega-amp spherical tokamak.

H-mode plasmas have been achieved on the MAST spherical tokamak at input power considerably higher than predicted by conventional threshold scalings. Following L- H transition, a clear improvement in energy confinement is obtained, exceeding recent international scalings even at densities approaching the Greenwald density limit. Transition is accompanied by an order-of-magnitude increase in edge-density gradient, a marked decrease in turbulence, the efficient conversion of internal electron Bernstein waves into free space waves, and the onset and saturation of edge poloidal rotation.

Journal Article↗
PubMed2001

Effects of transdermal testosterone gel on bone turnover markers and bone mineral density in hypogonadal men.

OBJECTIVE: Androgen replacement has been reported to increase bone mineral density (BMD) in hypogonadal men. We studied the effects of 6 months of treatment with a new transdermal testosterone (T) gel preparation on bone turnover markers and BMD. DESIGN: This was a prospective, randomized, multicentre, parallel clinical trial where 227 hypogonadal men, mean age 51 years (range: 19-68 years) were studied in 16 academic and research institutions in the USA. Subjects were randomized to apply 1% T gel containing 50 or 100 mg T (delivering approximately 5-10 mg T/day) or two T patches (delivering 5 mg T/day) transdermally for 90 days. At day 91, depending on the serum T concentration, the T gel dose was adjusted upward or downward to 75 mg T/day until day 180. No dose adjustment occurred in the T patch group. MEASUREMENTS: Serum T, free T and oestradiol, bone turnover markers and BMD were measured on days 0, 30, 90 and 180 before and after treatment. RESULTS: Application of T gel 100 mg/day resulted in serum T concentrations 1.4 and 1.9-fold higher than in the T gel 50 mg/day and the T patch groups, respectively. Proportional increases occurred in serum oestradiol. Urine N-telopeptide/creatinine ratio, a marker for bone resorption, decreased significantly (P = 0.0019) only in the T gel 100 mg/day group. Serum bone osteoblastic activity markers (osteocalcin, procollagen and skeletal alkaline phosphatase) increased significantly during the first 90 days of treatment without intergroup differences but declined to baseline thereafter. BMD increased significantly both in the hip (+1.1 +/- 0.3%) and spine (+2.2 +/- 0.5%) only in the T gel 100 mg/day group (P = 0.0001). CONCLUSIONS: Transdermal testosterone gel application for 6 months decreased bone resorption markers and increased osteoblastic activity markers for a short period, which resulted in a small but significant increase in BMD. Ongoing long-term studies should answer whether the observed increases in BMD are sustained or continue to be dependent on the dose of testosterone administered.

Administration, Cutaneous↗
PubMed2001

The variability in the interpretation of prenatal diagnostic ultrasound.

OBJECTIVES: Although prenatal ultrasound is broadly used to detect abnormal fetuses, the variability in the interpretation of second-trimester prenatal ultrasound examinations is unknown. We sought to evaluate the consistency of the interpretation of prenatal ultrasound examinations. DESIGN: Physicians who perform prenatal ultrasound and who participate in the California Maternal Serum Expanded AFP program were asked to interpret a series of test ultrasound examinations. The series of cases was selected to include a random sample of fetal structural abnormalities, ultrasound markers that have been associated with chromosomal abnormalities, and normal cases. Interobserver agreement was evaluated using a kappa statistic for each organ system. The sensitivity and false-positive rate were calculated for detecting specific anatomic abnormalities within each organ system. RESULTS: Of the 210 sonologists eligible for inclusion in the study, completed responses were received from 148 (70%). There was moderate to substantial agreement between physicians in reporting the presence of fetal abnormalities for all organ systems (kappa range 0.40-0.88, P < 0.001). The consistency was highest for the central nervous system (CNS), neck, and face. Within each organ system, the consistency was similar for major structural abnormalities and ultrasound markers of chromosomal abnormalities. The sensitivity ranged from 62% (95% confidence interval (CI) 58-66%) for major renal abnormalities to 91% (95% CI 88-94%) for CNS abnormalities, with corresponding false-positive rates of 7% (95% CI 6-9%) for renal abnormalities and 9% (95% CI 7-11%) for CNS abnormalities. For most organ systems, the sensitivity for detecting ultrasound markers of chromosomal abnormalities was similar to the sensitivity for detecting structural abnormalities. CONCLUSION: There is moderate to substantial agreement in the interpretation of second-trimester prenatal ultrasound examinations. Whether the identification of specific ultrasound abnormalities and markers is overall beneficial to patients remains to be determined.

Chromosome Aberrations↗
PubMed2001

Outbreak of Acinetobacter baumannii in an intensive care unit associated with tracheostomy.

A case-control study was conducted to determine risk factors for acquisition of an epidemic strain of Acinetobacter baumannii in an intensive care unit. The epidemic strain was identified by pulsed-field gel electrophoresis and was isolated from tracheal secretions in 13 (87%) of 15 patients. In a logistic regression analysis, presence of a tracheostomy was an independent risk for Acinetobacter sp acquisition (odds ratio, 421; 95% confidence interval, 13.8-12925; P =.001) and the strength of the association was inversely related to the duration of mechanical ventilation. The outbreak coincided with the introduction of a policy of early percutaneous tracheostomy in the intensive care unit and probably resulted from inadequate infection control practices during respiratory care. No environmental reservoir was found. Institution of contact precautions, enhanced handwashing, and staff education was associated with resolution of the outbreak.

Acinetobacter↗
PubMed2001

A randomized clinical trial to compare the effects of a heat and moisture exchanger with a heated humidifying system on the occurrence rate of ventilator-associated pneumonia.

BACKGROUND: The purpose of this study was to compare the performance of heat and moisture exchanger filters with heated humidifying systems in the mechanical ventilator circuit on the incidence of ventilator-associated pneumonia (VAP) and bacterial colonization. METHOD: Two hundred and forty-three consecutive patients who required mechanical ventilation for 48 hours or more in the adult intensive care unit were randomized to either a heat and moisture exchanger (HME) or a heated humidifying breathing circuit. RESULTS: The VAP rate among the group with HME was 11.4%; the rate among the group with heated humidifying system (HHS) was 15.8%. The difference was not statistically significant. Approximately 68% of the patients in the HME group had no pathogen isolated compared with 50% of the patients in the HHS group. This difference was statistically significant (P =.006). However, the distribution of the pathogens among those patients who had the isolated pathogens was mostly identical in the 2 groups. CONCLUSION: Even though the study did not find HME to be significantly advantageous over the HHS, in as much as VAP rate is concerned, other advantages such as reduced nurses workload, reduced financial cost, and better safety made HME a more favorable device for use in our adult intensive care unit.

Bacteria↗
PubMed2001

Methicillin-resistant Staphylococcus aureus: profiles oceans apart--Canadian and Saudi Arabian experiences.

Methicillin-resistant Staphylococcus aureus (MRSA), a pathogen which has increased over the past three decades, is responsible for nosocomial infections and adverse patient outcomes. It is a pathogen of global importance. Rates of patient colonization or infection vary greatly internationally. Lower rates have been observed in Canada and Saudi Arabia compared to the United States and United Kingdom. Although these lower rates may appear reassuring, the trend in MRSA observed in two capital cities, Winnipeg, Canada and Riyadh, Saudi Arabia are consistent with a widespread global increase in MRSA.

Canada↗
PubMed2001

Universal newborn screening for Hb H disease in California.

Newborn screening is an accepted public health measure to ensure that appropriate health care is provided in a timely manner to infants with hereditary/metabolic disorders. Alpha-thalassemia is a common hemoglobin (Hb) disorder, and causes Hb H (beta4) disease, and usually fatal homozygous alpha(0)-thalassemia, also known as Hb Bart's (gamma4) hydrops fetalis syndrome. In 1996, the State of California began to investigate the feasibility of universal newborn screening for Hb H disease. Initial screening was done on blood samples obtained by heel pricks from newborns, and stored as dried blood spots on filter paper. Hb Bart's levels were measured as fast-moving Hb by automated high-performance liquid chromatography (HPLC) identical to that currently used in newborn screening for sickle cell disease. Subsequent confirmation of Hb H disease was done by DNA-based diagnostics for alpha-globin genotyping. A criterion of 25% or more Hb Bart's as determined by HPLC detects most, if not all cases of Hb H disease, and few cases of alpha-thalassemia trait. From January, 1998, through June, 2000, 89 newborns were found to have Hb H disease. The overall prevalence for Hb H disease among all newborns in California is approximately 1 per 15,000. Implementation of this program to existing newborn hemoglobinopathy screening in populations with significant proportions of southeast Asians is recommended. The correct diagnosis would allow affected infants to be properly cared for, and would also raise awareness for the prevention of homozygous alpha(0)-thalassemia or Hb Bart's hydrops fetalis syndrome.

Asia, Southeastern↗
PubMed2001

Cystic fibrosis screening in newborns: results from existing programs.

Newborn screening for cystic fibrosis (CF) provides early identification and initiation of treatment to infants with this fatal and often misdiagnosed genetic disease. Although reports of health benefits continue to mount from decade-old screening programs in Wisconsin, France, and Australia, newborn screening for CF is still a highly debated topic in genetic policy development. This article summarizes the literature published between May 2000 and April 2001 regarding the health benefits, risks, cost-effectiveness, and programmatic issues of newborn screening for CF. The literature consistently shows evidence of benefits and lack of harm from newborn screening for CF.

Cost-Benefit Analysis↗
PubMed2000

Complete stabilization of neoclassical tearing modes with lower hybrid current drive on COMPASS-D. RF teams.

Lower hybrid current drive (LHCD) with modest powers ( approximately 10% of the total power input) has been used for the first time to completely stabilize performance limiting neoclassical tearing modes in many COMPASS-D tokamak discharges. The stabilizing effect in these experiments is consistent with a reduction in the free energy available in the current profile to drive tearing modes (i.e., the stability index, delta(')) resulting from favorable current gradients (from the LHCD driven current) around the rational surface.

Journal Article↗
PubMed2000

Antithrombin activity of medicinal plants of the Azores.

A chromogenic bioassay was utilized to determine the antithrombin activity of methylene chloride and methanol extracts prepared from 50 plants of Azores. Extracts of the six plants Hedychium gardneranum, Tropaeolum majus, Gunnera tinctoria, Hedera helix, Festuca jubata and Laurus azorica demonstrated activity of 78% or higher in this bioassay system.

Azores↗
PubMed2000

The incidence and risk factors of ventilator-associated pneumonia in a Riyadh hospital.

We report the incidence of, and risk factors for, ventilator-associated pneumonia (VAP) at the King Fahad National Guard Hospital. Of the 202 patients studied, 41 (25.2%) had VAP. The incidence density was 16.8/1,000 person-days of ventilation. Variables significantly associated with VAP were serious injury from motor-vehicle accident, enteral feeding, and length of ventilation. The avoidance of unnecessary enteral nutrition could help to reduce VAP.

Accidents, Traffic↗
PubMed2000

Use of the phenylalanine:tyrosine ratio to test newborns for phenylketonuria in a large public health screening programme.

OBJECTIVE: To assess the benefits of using the phenylalanine:tyrosine ratio to screen newborns for phenylketonuria (PKU). SETTING: Data were collected from all newborns in California during a ten month period (n = 404,381). METHODS: Dried blood spot specimens were analysed at nine laboratories. To assure that the results reported from multiple sites were matched accurately, an automated methodology was chosen that included sample processing, analysis, telecommunications, reporting, and information technology. Phenylalanine and tyrosine concentrations were measured independently by continuous flow fluorometry, for which precision, recovery, detection limits, carryover, chemical specificity, reportable range, and number of repeats are reported. RESULTS: In this study, 37% of the newborns were tested at less than 24 hours of age. For this population, using a phenylalanine only cut off of 200 mumol/l, there were 48 recalled infants per case of classic PKU. Using the phenylalanine:tyrosine ratio with a cut off of 1.50, screen positives could be reported with phenylalanine as low as 150 mumol/l and with only 12 recalls per case. CONCLUSIONS: The phenylalanine:tyrosine ratio can be measured accurately at multiple laboratories using two channel chemical analyses. Having applied the methods to the routine clinical screening of a large population, it was confirmed that the clinical sensitivity and specificity of the PKU screening test are higher when the phenylalanine:tyrosine ratio is incorporated into the cut off than when the cut off is based on the phenylalanine concentration alone.

California↗
PubMed2000

Long-term pharmacokinetics of transdermal testosterone gel in hypogonadal men.

Transdermal delivery of testosterone (T) represents an effective alternative to injectable androgens. Transdermal T patches normalize serum T levels and reverse the symptoms of androgen deficiency in hypogonadal men. However, the acceptance of the closed system T patches has been limited by skin irritation and/or lack of adherence. T gels have been proposed as delivery modes that minimize these problems. In this study we examined the pharmacokinetic profiles after 1, 30, 90, and 180 days of daily application of 2 doses of T gel (50 and 100 mg T in 5 and 10 g gel, delivering 5 and 10 mg T/day, respectively) and a permeation-enhanced T patch (2 patches delivering 5 mg T/day) in 227 hypogonadal men. This new 1% hydroalcoholic T gel formulation when applied to the upper arms, shoulders, and abdomen dried within a few minutes, and about 9-14% of the T applied was bioavailable. After 90 days of T gel treatment, the dose was titrated up (50 mg to 75 mg) or down (100 mg to 75 mg) if the preapplication serum T levels were outside the normal adult male range. Serum T rose rapidly into the normal adult male range on day 1 with the first T gel or patch application. Our previous study showed that steady state T levels were achieved 48-72 h after first application of the gel. The pharmacokinetic parameters for serum total and free T were very similar on days 30, 90, and 180 in all treatment groups. After repeated daily application of the T formulations for 180 days, the average serum T level over the 24-h sampling period (C(avg)) was highest in the 100 mg T gel group (1.4- and 1.9-fold higher than the C(avg) in the 50 mg T gel and T patch groups, respectively). Mean serum steady state T levels remained stable over the 180 days of T gel application. Upward dose adjustment from T gel 50 to 75 mg/day did not significantly increase the C(avg), whereas downward dose adjustment from 100 to 75 mg/day reduced serum T levels to the normal range for most patients. Serum free T levels paralleled those of serum total T, and the percent free T was not changed with transdermal T preparations. The serum dihydrotestosterone C(avg) rose 1.3-fold above baseline after T patch application, but was more significantly increased by 3.6- and 4.6-fold with T gel 50 and 100 mg/day, respectively, resulting in a small, but significant, increase in the serum dihydrotestosterone/T ratios in the two T gel groups. Serum estradiol rose, and serum LH and FSH levels were suppressed proportionately with serum T in all study groups; serum sex hormone-binding globulin showed small decreases that were significant only in the 100 mg T gel group. We conclude that transdermal T gel application can efficiently and rapidly increase serum T and free T levels in hypogonadal men to within the normal range. Transdermal T gel provided flexibility in dosing with little skin irritation and a low discontinuation rate.

Administration, Cutaneous↗
PubMed2000

Transdermal testosterone gel improves sexual function, mood, muscle strength, and body composition parameters in hypogonadal men.

Testosterone (T) therapy for hypogonadal men should correct the clinical abnormalities of T deficiency, including improvement of sexual function, increase in muscle mass and strength, and decrease in fat mass, with minimal adverse effects. We have shown that administration of a new transdermal T gel formulation to hypogonadal men provided dose proportional increases in serum T levels to the normal adult male range. We now report the effects of 180 days of treatment with this 1% T gel preparation (50 or 100 mg/day, contained in 5 or 10 g gel, respectively) compared to those of a permeation-enhanced T patch (5 mg/day) on defined efficacy parameters in 227 hypogonadal men. In the T gel groups, the T dose was adjusted up or down to 75 mg/day (contained in 7.5 g gel) on day 90 if serum T concentrations were below or above the normal male range. No dose adjustment was made with the T patch group. Sexual function and mood changes were monitored by questionnaire, body composition was determined by dual energy x-ray absorptiometry, and muscle strength was measured by the one repetitive maximum technique on bench and leg press exercises. Sexual function and mood improved maximally on day 30 of treatment, without differences across groups, and showed no further improvement with continuation of treatment. Mean muscle strength in the leg press exercise increased by 11 to 13 kg in all treatment groups by 90 days and did not improve further at 180 days of treatment. Moderate increases were also observed in arm/chest muscle strength. At 90 days of treatment, lean body mass increased more in the 100 mg/day T gel group (2.74 +/- 0.28 kg; P = 0.0002) than in the 50 mg/day T gel (1.28 +/- 0.32 kg) and T patch groups (1.20 +/- 0.26 kg). Fat mass and percent fat were not significantly decreased in the T patch group, but showed decreases in the T gel groups (50 mg/day, -0.90 +/- 0.32 kg; 100 mg/day, - 1.05 +/- 0.22 kg). The increase in lean mass and the decrease in fat mass were correlated with the changes in average serum T levels attained after transdermal T replacement. These beneficial effects of T replacement were accompanied by the anticipated increases in hematocrit and hemoglobin but without significant changes in the lipid profile. The increase in mean serum prostate-specific antigen levels (within the normal range) was correlated with serum levels of T. The greatest increases were noted in the 100 mg/day T gel group. Skin irritation was reported in 5.5% of subjects treated with T gel and in 66% of subjects in the permeation-enhanced T patch group. We conclude that T gel replacement improved sexual function and mood, increased lean mass and muscle strength (principally in the legs), and decreased fat mass in hypogonadal men with less skin irritation and discontinuation compared with the recommended dose of the permeation-enhanced T patch.

Administration, Cutaneous↗
PubMed1998

Yohimbine in neurally mediated syncope. Pathophysiological implications.

In this study, we evaluated if increased sympathetic stimulation is an essential requirement for the development of neurally mediated syncope (NMS) by manipulating overall sympathetic outflow in subjects susceptible to tilt-induced syncope. Eight previously characterized patients with recurrent NMS (five females and three males; 34+/-2 yr) were recruited from the Vanderbilt Syncope Unit and eight age-matched controls underwent initial administration of clonidine (CLO) or yohimbine (YHO). This was done, prospectively, to determine doses of these agents that would increase or decrease plasma norepinephrine levels by >/= 30%. On a different day, in all subjects we determined intraarterial blood pressure, EKG and muscle sympathetic nerve activity (MSNA) both supine and during upright tilt. After this, subjects randomly received either CLO or YHO, and 3 h later another tilt was performed. After 1 wk, a similar procedure with the other drug was performed. During the two basal tilts, all the control subjects completed the study, whereas all the NMS patients developed syncope. Reduction in sympathetic tone by CLO resulted in a decreased tolerance to tilt in three out of eight controls and in all the NMS patients. In contrast, YHO not only increased basal plasma NorEpi levels and MSNA, but also prevented syncope in seven out of eight patients. In a selected population of patients, increased sympathetic activity is not a prerequisite for the development of syncope. Yohimbine-induced enhancement of sympathetic tone in patients with NMS improves orthostatic tolerance and raises the possibility that this drug may be a useful agent in the treatment of NMS.

Adult↗