The radiologist as a palliative care subspecialist: providing symptom relief when cure is not possible.

OBJECTIVE: The purpose of this study was to determine the percentage of patients referred to an interventional radiology (IR) practice who need palliative care and to examine the training required for a diplomate of the American Board of Radiology (ABR) to qualify for the hospice and palliative medicine certifying examination. MATERIALS AND METHODS: This retrospective study reviewed all patient referrals to an academic vascular and IR practice during the month of August 2009. The demographics, underlying diagnosis, and the type of procedures performed were ascertained from the electronic medical record. The requirements for a diplomate of the ABR to obtain certification as a hospice and palliative medicine subspecialist were evaluated and summarized. RESULTS: Two-hundred eighty-two patients were referred to the IR service and underwent a total of 332 interventional procedures. Most of the patients (229 [81.2%]) had underlying diagnoses that would warrant consultation with a hospice and palliative medicine subspecialist; these patients were significantly older (58.5 vs 44.7 years; p < 0.01) and underwent more procedures (1.21 vs 1.02; p < 0.01). To obtain a subspecialty certification in hospice and palliative medicine, a radiologist needs certification by the ABR, an unrestricted medical license, 2 years of subspecialty training in hospice and palliative medicine, 100 hours of interdisciplinary hospice and palliative medicine team participation, active care of 50 terminally ill adult patients, and successful performance on the certification examination. CONCLUSION: Procedures related to palliative care currently compose the majority of our IR cases. Certification in hospice and palliative medicine can be achieved with a modest investment of time and clinical training.

Gas Phase Ion Chemistry to Determine Isoaspartate in a Peptide Backbone.

Proof of concept evidence is presented for a new method for the determination of isoaspartate, an important post-translational modification. Chemical derivatization is performed using common reagents for the modification of carboxylic acids and shown to yield suitable diagnostic information with regard to isomerization at the aspartate residue. The diagnostic gas phase chemistry is probed by collision-induced dissociation mass spectrometry, on the timescale of the MS experiment and semi-quantitative calibration of the percentage of isoaspartate in a peptide sample is demonstrated. Graphical Abstract ᅟ.

Serum and urine polyamines in normal and in short children.

The serum and urine polyamines putrescine, spermidine, and spermine were measured in 112 normal subjects from 0 to 70 yr of age, and in three groups of short children from 7 to 20 yr: 21 growth hormone (GH) deficient patients, 20 normal variant short stature children, and 9 girls with 45, X Turner's syndrome. Urine polyamines were expressed as micromoles per gram of creatinine or per kilogram body weight, and serum polyamines were expressed as nanomoles per milliliter. In normals, the three polyamines were highest in urine and serum at birth. The mean levels declined progressively with age, the rate of change decreasing with age. The mean for the normal subjects, and its 95% confidence and prediction intervals, were estimated from birth to age 70 for each serum and urine polyamine. In GH-deficient children, serum and urine values were significantly lower (P < 0.05) than the age-specific normal values (with the exception of serum spermidine and spermine), averaging 25-55% below normal. This abnormality was corrected during 1 wk of treatment with human GH. In Turner's syndrome, serum and urine values were significantly reduced (P < 0.05), averaging 35-80% below age-specific normals. GH treatment had no corrective effect. In 6 of 20 normal variant short stature children, polyamine levels were significantly (P < 0.01) subnormal, averaging 50-80% below age-specific normals in both serum and urine. Treatment with GH had no corrective effect. These data show that levels of polyamines in serum and urine are correlated with linear growth primarily during the first decade of life. Subnormal polyamine levels are generally associated with growth retardation.

Impaired growth hormone secretion in the adult population: relation to age and adiposity.

Growth hormone (GH) release was studied in adults of normal stature, ages 21-86 yr. The subjects were 85-115% of ideal body weight, between the 5th and 95th percentiles in height, and free of active or progressive disease. 9 to 12 individuals in each decade from thirds to ninth were evaluated. The following criteria of GH status were measured: serum GH concentration, analyzed by radioimmunoassay at half-hour intervals for 4 h after onset of sleep, and at 1-h intervals from 8 a.m. to 4 p.m. in 52 subjects; daily retention of N, P, and K in response to 0.168 U human (h)GH/kg body wt3/4/day in 18 subjects; and plasma somatomedin C (SmC) level before and during exogenous hGH treatment in 18 subjects. All 10 individuals, 20-29 yr old, released substantial amounts of endogenous GH during both day and night (average peak serum GH obtained during day and night was 7.3 and 20.3 ng/ml, respectively); average plasma SmC was 1.43 U/ml (95% tolerance limits, 0.64-2.22 U/ml). There was no significant effect of exogenous hGH on elemental balances or on plasma SmC. In contrast, 6 of 12 individuals 60-79 yr old showed the following evidences of impaired GH release; peak waking and sleeping serum GH less than 4 ng/ml; plasma SmC less than 0.38 U/ml; a significant retention in N, P, and K; and a significant rise in plasma SmC, in response to exogenous hGH. Plasma SmC, serum GH during sleep, serum GH during the day, retentions of N, P, and K in response to exogenous hGH, and rise in plasma SmC in response to hGH were all intercorrelated (P less than 0.05). Plasma SmC less than 0.38 U/ml corresponded to peak nocturnal serum GH less than 4 ng/ml. The prevalence of plasma SmC less than 0.38 U/ml increased progressively from age 20 to 90: third decade, 0%; fourth, 11%; fifth, 20%; sixth, 22%; seventh, 42%; eight, 55%; and ninth, 55%. Within each decade, plasma SmC was inversely related to adiposity.

Determination and pharmacology of a new hydroxylated metabolite of tamoxifen observed in patient sera during therapy for advanced breast cancer.

A new hydroxylated metabolite of tamoxifen, Metabolite Y [trans-1-(p-beta-hydroxyethoxyphenyl)-1,2-diphenylbut-1-ene] was characterized and subsequently measured by high-performance liquid chromatography in serum from patients receiving normal (10 mg twice daily) and high dose (greater than or equal to 150 mg twice daily) tamoxifen therapy for treatment of advanced breast cancer. In normal-dose patients, the serum level of Metabolite Y ranged between 6 and 60 ng/ml. This contrasted with serum levels of 80 to 180 ng/ml for tamoxifen and 200 to 300 ng/ml for N-desmethyltamoxifen, the major metabolite of tamoxifen. Serum levels of all three components were unchanged in one patient during the 24 hr after the cessation of tamoxifen therapy. Maximum serum levels of Metabolite Y were 800 ng/ml with concentrations of 1 micrograms/ml for tamoxifen and 2 micrograms/ml for N-desmethyltamoxifen in a patient on a 2-year course of high-dose therapy. Metabolite Y inhibited the binding of 17 beta-[3H]-estradiol to rat uterine and human breast carcinoma estrogen receptor. However, this metabolite was only weakly active: monohydroxytamoxifen [relative binding affinity (RBA) = 280]; tamoxifen (RBA = 6); Metabolite E (RBA = 3); N-desmethyltamoxifen (RBA = 4); Metabolite Y (RBA = 0.5). In 3-day immature rat uterine weight tests, Metabolite Y was a partial agonist with weak antiestrogenic activity. Although Metabolite Y has only weak activity, this compound would be expected to contribute to the overall antiestrogenic and antitumor properties of tamoxifen during therapy.

Predictors of progression from impaired glucose tolerance to NIDDM: an analysis of six prospective studies.

Risk factors associated with the progression from impaired glucose tolerance (IGT) to NIDDM were examined in data from six prospective studies. IGT and NIDDM were defined in all studies by World Health Organization (WHO) criteria, and baseline risk factors were measured at the time of first recognition of IGT. The studies varied in size from 177 to 693 participants with IGT, and included men and women followed from 2 to 27 years after the recognition of IGT. Across the six studies, the incidence rate of NIDDM was 57.2/1,000 person-years and ranged from 35.8/1,000 to 87.3/1,000 person-years. Although baseline measures of fasting and 2-h postchallenge glucose levels were both positively associated with NIDDM incidence, incidence rates were sharply higher for those in the top quartile of fasting plasma glucose levels, but increased linearly with increasing 2-h postchallenge glucose quartiles. Incidence rates were higher among the Hispanic, Mexican-American, Pima, and Nauruan populations than among Caucasians. The effect of baseline age on NIDDM incidence rates differed among the studies; the rates did not increase or rose only slightly with increasing baseline age in three of the studies and formed an inverted U in three studies. In all studies, estimates of obesity (including BMI, waist-to-hip ratio, and waist circumference) were positively associated with NIDDM incidence. BMI was associated with NIDDM incidence independently of fasting and 2-h post challenge glucose levels in the combined analysis of all six studies and in three cohorts separately, but not in the three studies with the highest NIDDM incidence rates. Sex and family history of diabetes were generally not related to NIDDM progression. This analysis indicates that persons with IGT are at high risk and that further refinement of risk can be made by other simple measurements. The ability to identify persons at high risk of NIDDM should facilitate clinical trials in diabetes prevention.

Central haemodynamic changes during lower body positive pressure in patients with congestive cardiac failure.

Fifteen patients with moderately severe and severe chronic congestive heart failure were studied to determine the central haemodynamic results of short term increases in lower body positive pressure. Central haemodynamic variables were determined by Swan-Ganz thermodilution catheterisation and arterial cannulation. Graded increases in lower body positive pressure were applied to supine patients using Medical Anti-Shock Trousers (MAST). Increasing lower body positive pressure by 25 mm Hg and 55 mm Hg caused increases in mean right atrial pressure (6.0 to 13.2 to 17.9 mm Hg; p less than 0.001 and p less than 0.0001 respectively) and mean pulmonary artery pressure (26.8 to 35.5 to 41.3 mm Hg; p less than 0.05 and p less than 0.01 respectively). No significant changes were seen in left heart filling pressures or in pulmonary vascular resistance. Furthermore, there were no significant increases in indices of cardiac work (cardiac index, left ventricular stroke work index, right ventricular stroke work index or cardiac power output) despite the increased right heart filling pressures. These results show that in patients with longstanding severe congestive heart failure, short term increases in cardiac return may increase right heart pressures but do not appear to cause either beneficial or detrimental changes in left heart haemodynamic indices.

Rat uterine growth and induction of progesterone receptor without estrogen receptor translocation.

The rat uterus responds to estradiol (E2) and E2 benzoate stimulation with an increase in progesterone receptor production and with growth. These responses were also elicited to varying degrees by a series of estrogenic (ICI 77,949 and ICI 47,699) and antiestrogenic triphenylethylene derivatives [tamoxifen (TAM), 4-hydroxy-TAM (4-OH-TAM), and 4-CH3-TAM]. These compounds have a range of affinities for the estrogen receptor (ER) and are able to compete with [3H]E2 binding in the uterus in vivo. Within 1-2 h of a sc injection of high affinity ligands (E2, E2B, and 4-OH-TAM), there was decrease in cytosol ER. This decrease was also observed with TAM, which is metabolized to 4-OH-TAM in vivo. In contrast, there was no decrease in cytosolic ER in animals treated with low affinity compounds (ICI 77,949, ICI 47,699, and 4-CH3-TAM) at any time before the onset of an estrogenic response. Furthermore, the nuclear ER increased after administration of a high affinity ligand (E2), as measured by exchange assay, but no increase in nuclear ER was observed after administration of low affinity ligands (ICI 77,949 and 4-CH3-TAM), although estrogenic responses were produced. From these data we have suggested a functional model to explain ER-mediated events in the rat uterus that supports the recent proposal that unoccupied ER is located in the nuclear compartment. In this model, the majority of unoccupied ER may reside in the nucleus in vivo; however, when the cells are disrupted in vitro, the unoccupied receptor or dissociation of low affinity ligand-ER complex causes unoccupied receptor to fall out of the nucleus and be incorporated into the cytosolic fraction. The high affinity ligand-ER complexes are retained in the nucleus. This would suggest that the apparent translocation of the ER from the cytoplasm to the nucleus may be an artifact. The data may reflect differential extraction of unoccupied receptors from the nucleus rather than transfer of receptor complexes to the nucleus.

Vertex-corrected blood pressure in black girls. Relation to obesity, glucose, and cations.

Correlates of resting blood pressure (BP) were explored among 32 inner-city, black girls, ages 11.7 to 13.9 years, a sample drawn from the second and fourth quartiles of the BP distribution in an earlier school survey. Customary BP measurements in the seated position were corrected for the height of the arterial column extending from the BP cuff to the top (vertex) of each girl's head. This vertex correction procedure has previously been shown to eliminate the childhood association between mean arterial pressure and age. Vertex-corrected systolic BP was correlated individually (p less than 0.03) with serum fasting glucose, ionized calcium, sodium, and calculated osmolality. The BP association with serum glucose did not persist after an oral sucrose challenge. Vertex-corrected diastolic BP was correlated individually (p less than 0.02) with serum ionized calcium and four indices of obesity, the best correlated of which was the subscapular skinfold (r = 0.66, p = 0.0001). Vertex-corrected BPs generally provided stronger correlations than customary (uncorrected) BPs with the variables of interest. Correlations with seated BPs were generally stronger than those with supine BPs. By multiple regression analysis, seated vertex-corrected systolic BP was related directly to serum fasting glucose and ionized calcium and inversely to pulse rate (R2 = 0.53). Seated vertex-corrected diastolic BP was related directly to subscapular skinfold and calculated osmolality (R2 = 0.54). Vertex correction may facilitate clinical or epidemiological studies of early hypertension.

Blood pressure, plasma volume, and catecholamine levels during enalapril therapy in blacks with hypertension.

The effect of enalapril, an antihypertensive inhibitor of angiotensin-converting enzyme, on plasma catecholamine levels and plasma volume (PV) has not been well established. In a randomized, double-blind study, 29 subjects (28 blacks and one white) received one of the following dosing regimens: hydrochlorothiazide (HCTZ), 25 mg twice a day (group 1; n = 12); enalapril, 10 mg twice a day (group 2; n = 12); or enalapril, 10 mg twice a day, with HCTZ, 25 mg twice a day (group 3; n = 5). Dosages were doubled after 4 wk if diastolic blood pressure was greater than or equal to 90 mm Hg. After 8 wk of therapy, supine blood pressure decreased by 24.1/16.0 mm Hg (systolic/diastolic) in group 1, by 10.8/4.0 mm Hg in group 2, and by 48.0/27.8 mm Hg in group 3. Mean values of supine plasma levels of norepinephrine, epinephrine, and dopamine did not change with therapy. PV fell 7.9% in group 1, 1.3% in group 2, and 5.0% in group 3. There were no correlations between changes in PV and blood pressure, but a decrease in PV correlated with an increase in plasma norepinephrine levels in the group treated with HCTZ alone (r = -0.65) and in all 29 subjects combined (r = -0.45). Enalapril alone was not very effective in lowering blood pressure in these subjects, but the combination of enalapril with HCTZ was very effective. There was no evidence of a direct effect of enalapril on the sympathetic nervous system or on PV.

Report of a National Institutes of Health--Centers for Disease Control and Prevention workshop on the feasibility of conducting a randomized clinical trial to estimate the long-term health effects of intentional weight loss in obese persons.

A workshop was convened in 1997 by the National Institutes of Health and the Centers for Disease Control and Prevention to consider the need for and feasibility of conducting a randomized clinical trial to estimate the long-term health effects of intentional weight loss in obese persons. Although the benefits of weight loss in obese individuals may seem obvious, little information is available showing that intentional weight loss improves long-term health outcomes. Observational studies may be unable to provide convincing answers about the magnitude and direction of the health effects of intentional weight loss. Workshop participants agreed that a well-designed randomized clinical trial could answer several questions necessary for developing a rational clinical and public health policy for treating obesity. Such information will ultimately provide needed guidance on the risks and benefits of weight loss to health care providers and payers, as well as to millions of obese Americans.

A method of screening for growth hormone deficiency using anthropometrics.

Among children less than 3rd percentile in height, less than 1% are deficient in endogenous growth hormone, while 80% have no recognizable organic cause for short stature, and are termed normal variants. This study investigated whether anthropometric evaluation can distinguish growth hormone-deficient from normal variant children. Height, weight, midarm circumference and 10 skinfold thicknesses were measured in 24 growth hormone-deficient and 26 normal variant children; indices of linear growth, adiposity, and lean body mass were derived from these. All these variables were analyzed statistically by discriminant analysis. This led to a screening formula, here called a "Z-function," based only on height and five skinfolds (abdomen, back, chest, knee, and calf). The Z-function classified correctly all but two growth hormone-deficients and two normal variants. Because of the small and possibly inhomogeneous sample, the particular formula developed here is not recommended for general use, but these preliminary findings show that a simple anthropometric screening test is indeed feasible, and could be useful in pediatric practice.

Remission of nephrotic syndrome in type 1 diabetes: long-term follow-up of patients in the Captopril Study.

In 1994, we reported a 3.4 +/- 0.8 year follow-up of the eight patients who experienced remission of nephrotic syndrome during the Collaborative Study Group-sponsored, multicenter trial of captopril therapy in patients with type 1 diabetes with nephropathy (Captopril Study). Of the 409 patients randomized to treatment on the Captopril Study, 108 had nephrotic syndrome (24-hour proteinuria >/= 3.5 g of protein) at baseline. Of these 108 patients, 8 experienced remission of nephrotic syndrome (proteinuria

Irradiated vaccines for helminth control in livestock.

For nearly 40 years, irradiated larval vaccines have been available for the control of parasitic bronchitis in cattle and sheep caused by Dictyocaulus spp. Despite research on a number of other host/parasite systems, no other vaccines have been commercially successful. Vaccination could provide a useful addition to other control methods in an integrated parasite management system where the criteria for vaccine success may not be complete control and sterile immunity, but a sufficient reduction in worm burden to decrease overall reinfection levels at the flock/herd level and, hence, prevent clinical disease and subclinical effects including production loss. Indeed, vaccination against Dictyocaulus spp. relies on continued natural infection to maintain levels of immunity. However, the difficulties of producing live larval vaccines are often cited as a reason why this line of research should not be pursued. This paper discusses some of the difficulties in vaccine production and offers some solutions and recommendations for those wishing to develop and register irradiated larval vaccines for other helminth diseases.

Determinants of preterm delivery in low-risk pregnancies. The RADIUS Study Group.

From 14,948 low-risk singleton pregnancies, we calculated incidence, risk ratios, and attributable risks for characteristics associated with spontaneous and medically induced preterm delivery. There were 754 women who gave birth prior to 37 weeks of gestation (50.4/1000 deliveries). The greatest fraction of the incidence of prematurity among low-risk pregnancies was due to unknown factors associated with carrying a first live birth, regardless of preterm delivery mechanism (i.e., spontaneous labor, PROM, medical intervention), with population-attributable risk percents (PAR%) ranging from 16.0 to 30.5%. Other than nulliparity, male sex of the fetus accounted for the greatest fraction of spontaneous labor-induced prematurity incidence (PAR% = 13.6%), and maternal age greater than 30 years or a positive urine culture accounted for the greatest fraction of PROM-induced prematurity incidence (PAR% = 7.9 and 6.7, respectively). All other risk factors for either preterm labor or PROM accounted for less than 5% of the incidence. Three characteristics explained a large fraction of medically induced prematurity: women over 150 pounds at the onset of pregnancy (PAR% = 23.8), a > or = 2+ prenatal urine protein (PAR% = 18.7%), and cigarette smoking during the first trimester (PAR% = 8.6). Our results suggest known risk factors may explain only a small fraction of spontaneous preterm delivery incidence in low-risk pregnancies.

Suppurative mediastinitis after open heart surgery. A case control study of risk factors.

Suppurative mediastinitis occurred in 68 of 9,965 patients (0.7 percent) who underwent median sternotomy at Emory University Hospital from 1973 through 1982. Case-control methodology was used to identify preoperative, intraoperative, and postoperative risk factors for the development of poststernotomy mediastinitis. The following 12 individually significant risk factors were identified by univariate analysis: preoperative factors: history of chronic obstructive pulmonary disease (COPD), history of prior sternotomy, pyuria, low ejection fraction, and high left ventricular end-diastolic pressure; intraoperative factors: valvular or aortic aneurysm surgery, prolonged bypass pump time, repeat placement on bypass, duration of surgery; and postoperative factors: surgical reexploration due to postoperative hemorrhage, cardiopulmonary resuscitation in the immediate postoperative period, prolonged time (greater than 48 hours) on mechanical ventilation. By logistic regression analysis, three of these factors were found to be associated independently with increased odds of developing mediastinitis: duration of surgery, history of COPD, and prolonged postoperative mechanical ventilation.

Prenatal and perinatal risk and protective factors for neonatal intracranial hemorrhage. National Institute of Child Health and Human Development Neonatal Research Network.

OBJECTIVE: To identify prenatal and perinatal risk and protective factors for grade III and IV intracranial hemorrhage (ICH) in 4795 singleton infants (weight, < or = 1500 g). METHOD: Prenatal and perinatal risk and protective factors for ICH were examined initially by univariate analysis and adjusted for year of birth, followed by multivariate logistic regression analysis that adjusted simultaneously for the effects of year of birth and prenatal and perinatal characteristics. SETTING: Seven tertiary care neonatal-perinatal centers. RESULTS: By univariate analysis, African-American race, prenatal care, older maternal age, hypertension or preeclampsia, antenatal steroid administration, cesarean section delivery, increasing birth weight, increasing gestational age, and female gender of the infant were protective prenatal or perinatal factors. Antepartum hemorrhage, the presence of labor, and breech presentation were perinatal factors that were associated with an increased risk of ICH. By using staged logistic regression, a model of combined prenatal and perinatal characteristics that influenced grade III and IV ICH was developed. Significant protective factors against ICH included a complete course of antenatal steroid therapy, African-American maternal race, female gender of the infant, hypertension or preeclampsia with no antepartum hemorrhage, increasing gestational age, and increasing birth weight. CONCLUSION: Antenatal steroid administration is a therapeutic intervention that is associated with a decreased risk for neonatal grade III and IV ICH.

Presence of the "Beaumont" protein in serum of oral contraceptive users.

The level of the "Beaumont" protein present in serum was measured by a population of 223 black and 76 Caucasian women with different exposures to oral contraceptives (OCs). No differences were found in the values in nonusers, past users, current users, or new users of OCs. The values were higher in black nonusers and users than in comparable Caucasian groups, suggesting a racial difference. A group of 55 thrombotic women were subclassified by type of thrombosis and exposure to OC therapy. No significant difference was seen between the values in thrombotic women exposed or not exposed to OCs. A similar result was obtained when the types of thrombosis (arterial or venous) were compared. These results do not confirm Beaumont's hypothesis that antibodies are induced by contraceptive steroids in a subgroup of women on OC therapy.

Availability of Haemonchus contortus L3 larvae on pasture at Kiboko: a semi-arid warm agro-climatic zone in Kenya.

A study was carried out to determine the availability of Haemonchus contortus L3 larvae on pasture in a semi-arid warm agro-climatic zone of Kenya. By means of tracer sheep, it was shown that no H. contortus L3 larvae were available on pasture during the dry periods of the year (July-October and February). They were only available on pasture during the rainy season (November-January and March-June). Sheep permanently grazed on the same pasture however, harboured adult H. contortus in their abomasa throughout the year indicating that the perpetuation of haemonchosis in livestock in this agro-climatic zone was greatly dependent on the ability of the parasite to survive in the host throughout all seasons.

Repetitive monomorphic ventricular tachycardia aborted by sleep.

A 43-year-old woman with a 12-year history of palpitation was found to have recurrent monomorphic ventricular tachycardia resistant to beta-blockade but abolished by sleep.