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Biomedical subjects

R A Parker

Publications and source records attributed to R A Parker.

At least 19 recordsLinked to original sources
PubMed2004

Evaluation of ability of biochemical markers of bone turnover to predict a response to increased doses of HRT.

Antiresorptive therapy is usually given in a fixed dose, and we hypothesized that some patients receiving standard doses of hormone replacement therapy (HRT) might benefit from a higher dose, particularly if their bone turnover decreases after increasing the dose of HRT. Eighty-eight women who had been receiving standard-dose (0.625 mg/day) conjugated equine estrogens (CEE) for at least one year were randomized to take either standard-dose (0.625 mg/day, n = 36) or high-dose (1.25 mg/day, n = 52) therapy. Subjects with a uterus were allowed to take either 10 mg of medroxyprogesterone cyclically or 5 mg daily, according to personal preference. Bone Mineral Density (BMD) and biochemical markers of bone turnover were followed for 2 years. Mean bone turnover decreased significantly (-4.1% to -19.1%) after 6 months of high-dose CEE. Decreases in serum BSAP (bone-specific alkaline phosphatase) and serum or urine NTX ( N-terminal telopeptide crosslink of type I collagen) on high-dose therapy were not predictive of an improvement in BMD, but a decrease in serum CrossLaps did predict an improvement in BMD. Mean change in BMD in subjects with a significant decrease in serum CrossLaps at the anteroposterior spine was 3.1% +/- 3.9% versus 1.2% +/- 2.9% for subjects with no significant change in CrossLaps, P < 0.02. There was, however, a wide range of changes in BMD in patients with or without a significant change in CTX on high-dose HRT, making it impossible to predict an improvement in BMD based on an individual's changes in turnover. Measuring of bone density and bone turnover with better precision might be more successful in guiding individual dosing of antiresorptive therapy.

Alkaline Phosphatase↗
PubMed2003

Sensitivity, specificity and accuracy of stress SPECT myocardial perfusion imaging for detection of coronary artery disease in the distribution of first-order branch vessels, using an anatomical matching of angiographic and perfusion data.

We sought to investigate the utility of stress single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) for the identification of coronary artery disease (CAD) in the distribution of first-order branch vessels. We evaluated 135 consecutive patients with coronary angiography and stress SPECT MPI. We anatomically matched angiography and SPECT to assess the sensitivity, specificity and accuracy of SPECT MPI for the detection of CAD in the distribution of first-order branches. Subgroup analysis for stress test performance and previous coronary artery bypass grafting (CABG) was also performed. The sensitivity, specificity and accuracy of stress SPECT MPI for the detection of CAD in the distribution of first-order branch vessels were all 67%. For isolated branch vessel CAD, stress SPECT MPI had a sensitivity of 44%. In patients without CABG, the sensitivity, specificity and accuracy for the detection of CAD in the distribution of first-order branch vessels were 71%, 67% and 68%, compared with 60%, 67% and 64% for patients with CABG. The sensitivity for isolated branch vessel CAD was 50% for patients without CABG, but only 29% for patients with CABG. The sensitivity and specificity for CAD in the distribution of branch vessels were similar for all patients for all stress test modalities and heart rate response (sensitivity, 64-69%; specificity, 61-69%). Stress SPECT MPI offers intermediate sensitivity, specificity and accuracy for the detection of CAD in the distribution of first-order coronary artery branch vessels. However, for isolated branch vessel CAD, stress SPECT has a lower sensitivity, particularly in patients with previous CABG.

Coronary Angiography↗
PubMed2002

A pilot randomized trial of oxandrolone in inclusion body myositis.

BACKGROUND: Inclusion body myositis (IBM) remains without effective therapy. As anabolic steroids have myotrophic properties, the authors studied whether a synthetic androgen, oxandrolone, would have efficacy in IBM. METHODS: A double-blind, placebo-controlled, crossover design was used. Patients received oxandrolone or placebo for 12 weeks followed by a minimum 2-month washout period, followed by 12 weeks of the alternative treatment. Maximal voluntary isometric contraction testing (MVICT), manual muscle testing (MMT), and functional performance testing were obtained before and after each treatment period, with the whole-body MVICT score as the primary outcome measure. RESULTS: Of 19 patients enrolled, 16 (14 men, 2 women; median age 68.5 years) had complete data for at least the first treatment period, with 13 completing the entire study. Whole-body MVICT improved by a median of 15.5 kg with drug and 4.1 kg with placebo (p = 0.06), whereas MMT demonstrated a median increase of 2.0 Medical Research Council points with drug and 0.9 point with placebo (p = 0.33). Upper-extremity MVICT demonstrated a significant treatment effect, with strength increasing a median 6.3 kg with drug vs 2.5 kg with placebo (p = 0.006). Stair climbing also increased a median of 1 step on average with drug versus no change with placebo (p < 0.001). Minimal adverse effects occurred. CONCLUSIONS: Oxandrolone had a borderline significant effect in improving whole-body strength and a significant effect in improving upper-extremity strength as measured by MVICT. Given these findings, further study of this drug, possibly in combination with an immunomodulating agent, is warranted.

Aged↗
PubMed2002

Ventrolateral preoptic nucleus contains sleep-active, galaninergic neurons in multiple mammalian species.

The ventrolateral preoptic nucleus (VLPO) is a group of sleep-active neurons that has been identified in the hypothalamus of rats and is thought to inhibit the major ascending monoaminergic arousal systems during sleep; lesions of the VLPO cause insomnia. Identification of the VLPO in other species has been complicated by the lack of a marker for this cell population, other than the expression of Fos during sleep. We now report that a high percentage of the sleep-active (Fos-expressing) VLPO neurons express mRNA for the inhibitory neuropeptide, galanin, in nocturnal rodents (mice and rats), diurnal rodents (degus), and cats. A homologous (i.e. galanin mRNA-containing cell group) is clearly distinguishable in the ventrolateral region of the preoptic area in diurnal and nocturnal monkeys, as well as in humans. Galanin expression may serve to identify sleep-active neurons in the ventrolateral preoptic area of the mammalian brain. The VLPO appears to be a critical component of sleep circuitry across multiple species, and we hypothesize that shrinkage of the VLPO with advancing age may explain sleep deficits in elderly humans.

Adult↗
PubMed2002

Racial differences in the frequency of symptoms and complications of gastro-oesophageal reflux disease.

BACKGROUND: A number of reports have suggested that there are substantial racial differences in the frequency of gastro-oesophageal reflux disease and its complications, but few studies have compared directly the frequency of this disorder amongst different racial groups. AIM: To explore the racial differences in the frequency of gastro-oesophageal reflux disease and its complications. METHODS: We reviewed endoscopy reports and medical records for data on race and complications of gastro-oesophageal reflux disease in 2,477 consecutive patients who had endoscopic examinations at the general endoscopy unit of an academic hospital. In addition, we prospectively interviewed 129 out-patients attending general medical clinics in the hospital and in an Asian community health centre in Boston to obtain data on race and gastro-oesophageal reflux disease symptoms. RESULTS: One or more gastro-oesophageal reflux disease complications (peptic oesophageal ulcer, stricture or Barrett's oesophagus) were observed in 267 of 2,174 white patients (12.3%), seven of 249 black patients (2.8%), one of 21 West Asian patients (4.8%) and none of 33 East Asian patients seen at the general endoscopy unit (P < 0.001); 34.6% of whites, 46.1% of blacks and 2.6% of East Asian patients interviewed claimed that they had heartburn (P < 0.01), but the term 'heartburn' was understood by only 34.6%, 53.8% and 13.2% of whites, blacks and East Asians, respectively (P < 0.01). CONCLUSIONS: Asian patients in Boston infrequently complain of heartburn, whereas heartburn is commonly reported by both white and black patients. Many patients do not understand the meaning of the term heartburn, however, and so physicians should be cautious when using the term during patient interviews. Complicated gastro-oesophageal reflux disease appears to be predominantly a disorder of whites.

Adult↗
PubMed2001

Validation of a model of left ventricular segmentation for interpretation of SPET myocardial perfusion images.

Several models of left ventricular segmentation have been developed that assume a standard coronary artery distribution, and are currently used for interpretation of single-photon emission tomography (SPET) myocardial perfusion imaging. This approach has the potential for incorrect assignment of myocardial segments to vascular territories, possibly over- or underestimating the number of vessels with significant coronary artery disease (CAD). We therefore sought to validate a 17-segment model of myocardial perfusion by comparing the predefined coronary territory assignment with the actual angiographically derived coronary distribution. We examined 135 patients who underwent both coronary angiography and stress SPET imaging within 30 days. Individualized coronary distribution was determined by review of the coronary angiograms and used to identify the coronary artery supplying each of the 17 myocardial segments of the model. The actual coronary distribution was used to assess the accuracy of the assumed coronary distribution of the model. The sensitivities and specificities of stress SPET for detection of CAD in individual coronary arteries and the classification regarding perceived number of diseased coronary arteries were also compared between the two coronary distributions (actual and assumed). The assumed coronary distribution corresponded to the actual coronary anatomy in all but one segment (#3). The majority of patients (80%) had 14 or more concordant segments. Sensitivities and specificities of stress SPET for detection of CAD in the coronary territories were similar, with the exception of the RCA territory, for which specificity for detection of CAD was better for the angiographically derived coronary artery distribution than for the model. There was 95% agreement between assumed and angiographically derived coronary distributions in classification to single- versus multi-vessel CAD. Reassignment of a single segment (segment #3) from the LCX to the LAD territory further improved the model's fit with the anatomic data. It is concluded that left ventricular segmentation using a model with assumed coronary artery distribution is valid for interpretation of SPET myocardial perfusion imaging.

Coronary Angiography↗
PubMed2001

Effects of NHE-1 inhibition on cardioprotection and impact on protection by K/Mg cardioplegia.

BACKGROUND: Cardiac sodium hydrogen exchanger isoform-1 (NHE-1) activity during ischemia/reperfusion contributes to myocardial injury. The effects of NHE-1 inhibition during ischemia or reperfusion and on the protection afforded by K/Mg cardioplegia was unknown. METHODS: Rabbit hearts were used for Langendorff perfusion. Control hearts were perfused for 180 minutes. Global ischemia (GI) hearts received 30 minutes normothermic global ischemia and 120 minutes reperfusion. K/Mg hearts received cardioplegia 5 minutes before ischemia. Separate groups of GI and K/Mg hearts received the NHE-1 inhibitor, HOE-642, before ischemia (HOE-642-I), at the immediate start of reperfusion (HOE-642-R), or both before ischemia and at the immediate start of reperfusion (HOE-642-IR). RESULTS: Left ventricular peak developed pressure was significantly increased in HOE-I, HOE-R, and HOE-IR throughout reperfusion (p < 0.05 versus GI). Infarct size was significantly decreased (p < 0.05 versus GI) in all groups, but was significantly increased in HOE-R as compared with HOE-IR (p < 0.05). NHE-1 inhibition with K/Mg cardioplegia significantly decreased left ventricular peak developed pressure after 90 minutes of reperfusion (p < 0.05 versus K/Mg), with no significant effect on infarct size. CONCLUSIONS: NHE-1 inhibition used alone provides cardioprotection with optimal effects being observed with HOE-IR. NHE-1 inhibition with K/Mg cardioplegia decreases postischemic functional recovery during late reperfusion.

Animals↗
PubMed2001

Why do older women discontinue hormone replacement therapy?

Postmenopausal women who choose hormone replacement therapy (HRT) often discontinue this therapy within 1 year. Few studies have considered why older women (aged > or =65 years) discontinue therapy. To investigate this question and its relationship to HRT-related side effects, we analyzed data collected during the 3-month open-label (active HRT and alendronate placebo) run-in phase of a clinical trial for osteoporosis prevention and treatment in older women. Among women discontinuing the trial, we ascertained a primary reason based on the patients' records and classified it as related or unrelated to HRT. The incidence of specific HRT-related side effects reported during the run-in phase was abstracted from the trial database and compared between patients continuing in the trial and those discontinuing for HRT-related reasons. Of the 485 women who began the 3-month run-in phase, 112 (23%) discontinued the trial. Specifically, 73 (15%) women discontinued for reasons considered HRT related. Breast swelling/tenderness (26 women) and bloating (9 women) were more often primary reasons for discontinuation than were bleeding or spotting (7 women). Comparing all reported side effects, bloating was more common in women discontinuing because of HRT than in women continuing in the trial (18% versus 3%, p < or = 0.001), whereas other complaints were similar or lower: breast swelling/tenderness (59% versus 67%, p > 0.05), bleeding (16% versus 17%, p > 0.05), spotting (23% versus 41%, p < or = 0.05). Bloating, of which women discontinuing complained significantly more often, and breast swelling/tenderness, the most frequently cited primary reason for discontinuation, may be more important factors than bleeding or spotting in an older woman's decision to discontinue HRT.

Aged↗
PubMed2001

Variability of viral load in plasma of rhesus monkeys inoculated with simian immunodeficiency virus or simian-human immunodeficiency virus: implications for using nonhuman primate AIDS models to test vaccines and therapeutics.

Viral RNA level in plasma is a sensitive experimental endpoint for evaluating the efficacy of AIDS vaccines or therapies in nonhuman primates. By quantifying viral RNA in the plasma of 77 rhesus monkeys for 10 weeks after inoculation with simian-human immunodeficiency virus 89.6P (SHIV-89.6P) or simian immunodeficiency virus mac 251 (SIVmac 251), we estimated variability in three viral load (VL) measures: peak VL, the postacute set point VL, and VL decline from peak. Such estimates of biological variability are essential for determining the number of animals needed per group and may be helpful for selecting the most appropriate measure to use as the experimental endpoint. Peak VL was positively correlated with set point VL for both viruses. Variability (standard deviation) was substantially higher in monkeys infected with SIVmac 251 than in those infected with SHIV-89.6P for set point VL and VL decline. The variability of peak VL was less than one-half that of set point VL variability and only about two-thirds of that of VL decline, implying that the same treatment-related difference in peak VL could be detected with fewer animals than set point VL or VL decline. Thus, differences in VL variability over the course of infection and between viruses need to be considered when designing studies using the nonhuman primate AIDS models.

AIDS Vaccines↗
PubMed2001

False-positive screening mammograms: effect of immediate versus later work-up on patient stress.

PURPOSE: To compare the stress experienced by women who had false-positive screening mammograms and had undergone immediate on-site diagnostic imaging evaluation with that experienced by those who had been recalled for subsequent imaging. MATERIALS AND METHODS: A retrospective survey was mailed to women with false-positive screening mammograms that had proved negative or benign at diagnostic imaging. The women were divided into (a) those who had undergone diagnostic imaging during the same appointment as their screening examination and (b) those who had returned at a later date for work-up. The survey included questions about stress that was related to the screening and diagnostic experiences, how subjects had been notified about screening results, and their breast health histories. RESULTS: From the group that had undergone immediate work-up (n = 100), 50 eligible surveys were received; 71 were received from women who had undergone later work-ups (n = 176). The self-reported overall stress was significantly greater (P =.027) in the group recalled for subsequent diagnostic imaging. Among all respondents, stress from a false-positive screening result was greatest in women younger than 50 years of age with a positive first-degree family history of breast cancer. CONCLUSION: Providing immediate on-site diagnostic evaluation can reduce the stress of a false-positive screening mammogram.

Adult↗
PubMed2001

Changes in motor cortex activation after recovery from spinal cord inflammation.

Diseases of the spinal cord are associated with reactive changes in cerebral cortex organization. Many studies in this area have examined spinal cord conditions not associated with recovery, making it difficult to consider the value of these cortical events in the restoration of neurological function. We studied patients with myelitis, a syndrome of transient spinal cord inflammation, in order to probe cortical changes that might contribute to recovery after disease of the spinal cord. Seven patients, each of whom showed improvement in hand motor function after a diagnosis of myelitis involving cervical spinal cord, were clinically evaluated then studied with functional MRI. During right and left index finger tapping, activation volumes were assessed in three cortical motor regions within each hemisphere. Results were compared with findings in nine control subjects. Compared to the control group, myelitis patients had larger activation volumes within contralateral sensorimotor as well as contralateral premotor cortex. The degree of daily hand use showed a significant correlation with the volume of activation in contralateral sensorimotor cortex. Recovery from myelitis is associated with an enlarged activation volume in contralateral motor cortices. This change in motor cortex function is related to behavioral experience, and thus may contribute to motor improvement. The expanded activation in motor cortex, seen with several forms of spinal cord insult may have maximal utility when corticospinal tract axons are preserved.

Adult↗
PubMed2001

Bone loss in men with prostate cancer treated with gonadotropin-releasing hormone agonists.

Prostate cancer is the most common visceral malignancy in men. As the tumor is testosterone dependent, a frequent treatment modality involves therapy with GnRH agonists (GnRH-a) resulting in hypogonadism. Because testosterone is essential for the maintenance of bone mass in men, we postulated that GnRH-a therapy would negatively impact skeletal integrity. We compared bone mineral density (BMD), biochemical markers of bone turnover, and body composition in 60 men with prostate cancer (19 men receiving GnRH-a therapy and 41 eugonadal men) and BMD in 197 community-living healthy controls of similar age. BMD was assessed by dual energy x-ray absorptiometry and ultrasound. Biochemical markers of bone turnover, included markers of bone resorption (urinary N-telopeptide) and bone formation markers (bone-specific alkaline phosphatase and osteocalcin). Body composition (total body fat and lean body mass) was assessed by dual energy x-ray absorptiometry. Significantly lower BMD was found at the lateral spine (0.69 +/- 0.17 vs. 0.83 +/- 0.20 g/cm(2); P < 0.01), total hip (0.94 +/- 0.14 vs. 1.05 +/- 0.16 g/cm(2); P < 0.05), and forearm (0.67 +/- 0.11 vs. 0.78 +/- 0.07 g/cm(2); P < 0.01) in men receiving GnRH-a compared with the eugonadal men with prostate cancer. Significant differences were also seen at the total body, finger, and calcaneus (all P < 0.01). BMD values in eugonadal men with prostate cancer and healthy controls were similar. Markers of bone resorption (urinary N-telopeptide) and bone formation (bone-specific alkaline phosphatase) were elevated in men receiving GnRH-a therapy compared with those in eugonadal men with prostate cancer. Men receiving GnRH-a also had a higher percent total body fat (29 +/- 5% vs. 25 +/- 5%; P < 0.01) and lower percent lean body weight (71 +/- 5% vs. 75 +/- 5%; P < 0.01) compared with eugonadal men with prostate cancer. In conclusion, men with prostate cancer receiving androgen deprivation therapy have a significant decrease in bone mass and increase in bone turnover, thus placing them at increased risk of fracture.

Aged↗
PubMed2001

Instant vertebral assessment: a noninvasive dual X-ray absorptiometry technique to avoid misclassification and clinical mismanagement of osteoporosis.

The presence of a vertebral fracture significantly increases the risk of future fracture, classifies a patient with "clinical" osteoporosis, and usually results in treatment for osteoporosis. However, the majority of vertebral fractures are silent, and lateral X-rays (the standard method for identification) are not routinely obtained. Instant vertebral assessment (IVA), a technology that utilizes dual X-ray absorptiometry (DXA), provides rapid assessment of vertebral fractures and is highly correlated with vertebral fractures, as assessed on standard lateral spine X-rays. To assess the role of IVA in patient management, we examined standard bone mineral density (BMD) of the spine, total hip, and femoral neck and spine IVA by DXA in 482 participants screened for an osteoporosis study, who had no previous knowledge of vertebral fractures. Using World Health Organization (WHO) guidelines, subjects were classified using BMD at the spine, total hip, femoral neck, or any combination of these central sites. In addition, we considered subjects as osteoporotic if they had vertebral fractures independent of low bone density. We found that vertebral fractures assessed by IVA were present in 18.3% of asymptomatic postmenopausal women recruited for this study. The sensitivity of BMD alone to diagnose osteoporosis based on either a vertebral fracture or low BMD using WHO criteria ranged from 40 to 74%. This means that between 26 and 60% of osteoporotic individuals could have potentially been missed. Furthermore, 11.0-18.7% of clinically osteoporotic individuals would have been classified as normal by BMD criteria alone. We conclude that IVA is a useful adjunct in the clinical identification of osteoporosis and may prevent mismanagement of osteoporotic patients.

Absorptiometry, Photon↗
PubMed2001

Respiratory syncytial virus infection does not increase allergen-induced type 2 cytokine production, yet increases airway hyperresponsiveness in mice.

Severe respiratory syncytial virus (RSV)-induced disease is associated with childhood asthma and atopy. We combined murine models of allergen-sensitization and RSV infection to explore the interaction of allergic and virus-induced airway inflammation and its impact on airway hyperresponsiveness (AHR). We found that RSV infection during ova-sensitization (OVA/RSV) increased and prolonged AHR compared to mice only RSV-infected (RSV) or ova-sensitized (OVA). AHR is known to be associated with an increase in Type 2 cytokines (IL-4, IL-5, and IL-13) in allergen-sensitized mice. Therefore, we hypothesized that RSV-induced enhancement of AHR was a result of potentiating the Type 2 cytokine profile promoted by ova-sensitization. Surprisingly, we found that Type 2 cytokines induced by ova-sensitization were not increased by RSV infection despite the increase in AHR, and in some cases were diminished. RNAse protection assay revealed no difference in IL-4 and IL-5 mRNA levels between the OVA and OVA/RSV groups, and IL-13 mRNA was significantly decreased in the OVA/RSV mice compared to the OVA group. Flow cytometric analysis of Type 2 cytokines demonstrated the same frequency of IL-4 and IL-5 production in lung-derived T lymphocytes from the OVA/RSV and OVA groups. Direct cytokine ELISA measurements of lung supernatant showed the level of IL-13 was significantly decreased in the OVA/RSV group compared to OVA mice, while there was no difference in either IL-4 or IL-5 between these two groups. These data indicate that the enhanced and prolonged AHR caused by the interaction of allergic airway inflammation and virus-induced immune responses is a complex process that can not be explained simply by augmented production of Type 2 cytokines.

Allergens↗