Biomedical subjects

Shelley Hurwitz

Publications and source records attributed to Shelley Hurwitz.

At least 19 recordsLinked to original sources

PubMed2007

The role of education in biostatistical consulting.

Medical students, residents, postdoctoral fellows, and faculty commonly consult with biostatistical experts about study design and data analysis when conducting clinical research. The role of biostatistical training during these consultations is examined, and characterizations of the connections between biostatistical consultation and education are reviewed. The presence and kinds of teaching efforts during biostatistical consults at four academic research institutions over various periods of time between 1999 and 2005 (237 consultations in total) were recorded and are described. By site, 67, 70, 78, and 100 per cent of the consulting sessions included biostatistical training, with an overall 78 per cent (95 per cent CI: 73-83 per cent) of consultations including an educational component when all consultations were combined. Training covered a wide range of biostatistical topics. Seventy-five per cent of the consultations with faculty (120/161), 79 per cent with fellows and residents (31/39), and 100 per cent with medical students (10/10) included some degree of instruction in study design or statistical analysis topics. Results show that both the need and the opportunity exist for specialized biostatistical instruction during one-on-one sessions between a consulting biostatistician and physicians, medical students, and research staff. Academic researchers are ideally positioned to absorb this kind of training when they initiate a request for assistance with their own research project.

Biometry↗

PubMed2006

Evaluation of the nonneoplastic pathology in tumor nephrectomy specimens: predicting the risk of progressive renal failure.

Pathologic changes in nonneoplastic renal parenchyma of nephrectomy specimens for renal tumors and the significance of these changes with regard to the outcome of contralateral kidney function have not been studied previously. We examined the nonneoplastic renal parenchymal changes in 110 consecutive tumor nephrectomy specimens, and we correlated our findings with patients' clinical information. The material was examined for the presence of any glomerular, tubulointerstitial, or vascular pathology. In our analysis, only about 10% of cases had unremarkable renal parenchyma and vasculature. A further 28% of cases had unremarkable parenchyma, but some degree of vascular sclerosis was noted. The remaining cases (>60%) had evident pathologic abnormalities, most commonly related to vascular disease or diabetes mellitus. Regardless of the type of renal cancer they have, the majority of our cases can be placed in one of three principal groups: 1) unremarkable kidney parenchyma, with or without vascular sclerosis (38%); 2) parenchymal scarring and marked vascular changes, including cases of atheroembolic disease, and chronic thrombotic microangiopathy (28%); and 3) changes related to diabetes mellitus, such as glomerular hypertrophy, mesangial expansion, and diffuse glomerulosclerosis (24%). Follow-up data on serum creatinine 6 months postoperatively were available in a third of our patients. Patients with severe histopathologic findings (parenchymal scarring with >20% global glomerulosclerosis and advanced diffuse diabetic glomerulosclerosis) showed a significant change in serum creatinine from the preoperative period to 6 months after radical nephrectomy (P=0.001), indicative of progressive worsening of renal function; this change is significantly greater than that seen in patients with unremarkable renal parenchyma (P=0.01). We conclude that adequate examination of nonneoplastic renal parenchyma is an important tool in recognizing patients at risk for progressive renal disease after nephrectomy and could be an essential step in providing early preventive and treatment measures and better medical care of patients undergoing nephrectomy for neoplastic processes.

Adult↗

PubMed2006

Why is orthostatic tolerance lower in women than in men? Renal and cardiovascular responses to simulated microgravity and the role of midodrine.

BACKGROUND: Exposure to microgravity induces cardiovascular deconditioning, manifested by orthostatic intolerance (OI). We assessed the renal, cardioendocrine, and cardiovascular responses of women and men to simulated microgravity to examine the impact of gender on OI. METHODS: Fifteen healthy female and 14 healthy male subjects were given a constant diet for 3 to 5 days, after which they underwent a tilt-stand test (pre-TST) and began 14 to 16 days of head-down tilt bed rest (HDTB), followed by a repeat tilt-stand test (post-TST). Female subjects began HDTB so that the post-TST was at the same time in their menstrual cycle as their pre-TST. Twenty-four-hour urine collections (daily), hormonal measurements, plethysmography, and cardiovascular system identification were performed. RESULTS: The times to presyncope were significantly different for men and women before (p= .005) and after HDTB (p= .001), with all of the women but only 50% of the men experiencing presyncope during the pre-TST (p= .002) and all of the women but only 64% of the men experiencing presyncope during the post-TST. At baseline, the following differences between women and men were observed: women had higher serum aldosterone levels (p = .02), higher parasympathetic responsiveness (p = .01), lower sympathetic responsiveness (p = .05), and lower venous compliance (p = .05). Several parameters changed with HDTB in both men and women. In a double-blinded randomized trial, midodrine (5 mg orally) or placebo given to female subjects 1 hour before post-TST was ineffective in preventing 01. CONCLUSION: In conclusion, the frequency of OI is higher in women than in men and is not modified by midodrine at the dose used. This increased susceptibility is likely secondary to intrinsic basal differences in the activity of volume-mediated parasympathetic and adrenergic systems and in venous tone. Thus, approaches to reduce OI in women are likely to differ from those effective in men.

Adaptation, Physiological↗

PubMed2005

Aspirin has a gender-dependent impact on antiinflammatory 15-epi-lipoxin A4 formation: a randomized human trial.

OBJECTIVE: Aspirin blocks thromboxane production that contributes to its well-appreciated antiplatelet action. Aspirin also initiates the biosynthesis of novel antiinflammatory mediators from arachidonic acid, namely aspirin-triggered 15-epi-lipoxin A4. We recently conducted a double-blinded clinical trial with healthy subjects in whom low-dose aspirin (81 mg daily) significantly increased aspirin-triggered 15-epi-lipoxin A4 and concomitantly inhibited thromboxane. Here, we assessed whether plasma aspirin-triggered 15-epi-lipoxin A4 was age or gender dependent in subjects taking low-dose aspirin. METHODS AND RESULTS: A total of 128 subjects were allocated to: placebo, 81, 325, or 650 mg daily aspirin for an 8-week period. Plasma thromboxane B2 and aspirin-triggered 15-epi-lipoxin A4 were assessed from blood collected at baseline and the conclusion of the trial. We then performed a post-trial analysis in the group receiving low-dose aspirin. In female subjects, we found a positive correlation between age and aspirin-triggered 15-epi-lipoxin A4(increase of 0.37 ng/mL per decade), and a negative correlation was observed in men (decrease of 0.29 ng/mL per decade). These trends were significantly different from each other (P=0.045). CONCLUSIONS: Low-dose aspirin has a gender-specific impact on aspirin-triggered 15-epi-lipoxin A4 production, which may contribute to the gender-dependent clinical benefits of aspirin. Also, they may provide a molecular rationale for low-dose aspirin therapies in elderly women to reduce inflammation-related disorders.

Acetylation↗

PubMed2005

Aggregation of high-normal thyroid-stimulating hormone in hypertensive families.

BACKGROUND: Studies suggest that there are genetic variants that influence both blood pressure regulation and serum TSH levels. We investigated whether high-normal TSH values aggregate in hypertensive families. The influence of hypertension family history on serum TSH levels in healthy normotensive individuals was also examined. METHODS: All subjects were euthyroid (TSH, 0.5-5.0 mIU/liter). The study subjects were 333 hypertensives, including 229 members of multiple sibling families. The subjects had blood samples for serum TSH determination drawn in the morning after overnight bed rest. High-normal TSH was defined as values above 2.0 mIU/liter and equal to or less than 5.0 mIU/liter. Thirty-one healthy normotensives provided information about their family history of hypertension by telephone. RESULTS: The concordance for high-normal TSH values among hypertensive, multiple sibling families was greater than expected by chance (P = 0.009). There were nearly twice as many families concordant for high-normal TSH status as expected (13.2% vs. 7.0%), whereas the observed proportion concordant for normal TSH status was similar to that expected (58.3% vs. 54.1%). Family membership explained a significant proportion of variance in TSH status (P = 0.038). Healthy normotensives with a family history of hypertension had significantly higher TSH values (2.2 +/- 1.2 mIU/liter) than those with a negative family history of hypertension (TSH 1.3 +/- 0.7 mIU/liter) independent of other characteristics (P = 0.025). CONCLUSIONS: There is familial aggregation of high-normal TSH values in hypertensive families, and a hypertension family history influences serum TSH levels in healthy individuals. These findings are consistent with the existence of genetic variants affecting both blood pressure regulation and serum TSH levels.

Adult↗

PubMed2005

Quantitative morphometry of lupus nephritis: the significance of collagen, tubular space, and inflammatory infiltrate.

BACKGROUND: Lupus nephritis encompasses a wide range of parenchymal injuries and severity. Better predictors of outcome are needed for patients newly diagnosed with lupus nephritis, so that an appropriate management strategy may be selected. METHODS: A single-center cohort of first renal biopsies for lupus nephritis was chosen. Histologic sections of whole biopsy cores were stained with picro-Sirius red, and light microscopic images (x100) were digitally captured. Using a simple, freely available software package, the cortex of each biopsy was evaluated for four different parameters: area occupied by nuclei, intratubular space, fibrillary collagen, and collagenous matrix. Clinical and laboratory data were collected retrospectively from the time of biopsy and throughout follow-up. RESULTS: A high nuclear index at initial biopsy correlated with clinical parameters of disease activity, at the time of biopsy. High collagen matrix index predicted both relapse and progression to end-stage renal disease (ESRD). The fibrillary collagen index predicted progressive disease as assessed by doubling of serum creatinine, and relapse. Increased tubular space also predicted progressive disease as determined by doubling of creatinine and renal death. CONCLUSION: A simple automated system for objectively scoring biopsies of lupus nephritis predicts renal survival and may provide a useful adjunct to guide patient management.

Adult↗

PubMed2005

Simulated microgravity induces microvolt T wave alternans.

BACKGROUND: There are numerous anecdotal reports of ventricular arrhythmias during spaceflight; however, it is not known whether spaceflight or microgravity systematically increases the risk of cardiac dysrhythmias. Microvolt T wave alternans (MTWA) testing compares favorably with other noninvasive risk stratifiers and invasive electrophysiological testing in patients as a predictor of sudden cardiac death, ventricular tachycardia, and ventricular fibrillation. We hypothesized that simulated microgravity leads to an increase in MTWA. METHODS: Twenty-four healthy male subjects underwent 9 to 16 days of head-down tilt bed rest (HDTB). MTWA was measured before and after the bed rest period during bicycle exercise stress. For the purposes of this study, we defined MTWA outcome to be positive if sustained MTWA was present with an onset heart rate<or=125 bpm. During various phases of HDTB, the following were also performed: daily 24-hour urine collections, serum electrolytes and catecholamines, and cardiovascular system identification (measure of autonomic function). RESULTS: Before HDTB, 17% of the subjects were MTWA positive [95%CI: (0.6%, 37%)]; after HDTB, 42% of the subjects were MTWA positive [95%CI: (23%, 63%)] (P=0.03). The subjects who were MTWA positive after HDTB compared with MTWA negative subjects had an increased versus decreased sympathetic responsiveness (P=0.03) and serum norepinephrine levels (P=0.05), and a trend toward higher potassium excretion (P=0.06) after bed rest compared to baseline. CONCLUSIONS: HDTB leads to an increase in MTWA, providing the first evidence that simulated microgravity has a measurable effect on electrical repolarization processes. Possible contributing factors include loss in potassium and changes in sympathetic function.

Adult↗

PubMed2005

Readaptation from simulated microgravity as a stimulus for improved orthostatic tolerance: role of the renal, cardioendocrine, and cardiovascular systems.

BACKGROUND: Microgravity and simulated microgravity (SM) lead to important changes in orthostatic tolerance (OT), the autonomic nervous system (ANS), and the volume-regulating systems. After one is exposed to microgravity or SM, a period of readaptation to gravity is known to take place, but it is not certain if orthostatic function returns to baseline within the initial recovery and what mechanisms are involved. We hypothesized that after a period of recovery, OT, ANS, and volume-regulating systems would return to pre-SM levels. METHODS: To test this hypothesis, 24 healthy men were placed on a constant diet for 3 to 5 days, after which a tilt-stand test (pre-TST) was performed. The TST was repeated after 14 to 16 days of head-down tilt bed rest (HDTB) (post-TST) and a 3-day period of recovery (rec-TST), at which times measurements of renal, cardioendocrine, and cardiovascular systems were conducted. RESULTS: Presyncope occurred in 46% of subjects pre-TST, in 72% post-TST, and in 23% during rec-TST. OT was significantly better during the recovery period than at baseline (p = .03). There was a significant decrease in urinary sodium and potassium excretion, along with a decrease in plasma renin activity and serum and urine aldosterone compared with baseline. Serum norepinephrine and sympathetic responsiveness remained below baseline values. CONCLUSION: In summary, OT improved compared with baseline after a period of readaptation. Retention of electrolytes (sodium, potassium) could be involved. These findings indicate that recovery after SM is not simply a gradual return to baseline values but is instead a dynamic process reflecting interaction of multiple regulatory systems.

Adaptation, Physiological↗

PubMed2004

Aspirin triggers antiinflammatory 15-epi-lipoxin A4 and inhibits thromboxane in a randomized human trial.

There is increasing evidence that aspirin initiates biosynthesis of novel antiinflammatory mediators by means of interactions between endothelial cells and leukocytes. These mediators are classified as aspirin-triggered 15-epi-lipoxins. Such compounds may account at least in part for aspirin's clinical benefits, which are distinct from the well appreciated action of aspirin as a platelet inhibitor. Here, we addressed whether aspirin-triggered 15-epilipoxinA4 (ATL) formation is aspirin-dependent in humans and its relationship to aspirin's antiplatelet activity. We conducted a randomized clinical trial among 128 healthy subjects allocated to placebo or to 81-, 325-, or 650-mg daily doses of aspirin for 8 weeks. Plasma thromboxane (TX)B2, an indicator of platelet reactivity, and ATL were assessed from blood collected at baseline and at 8 weeks. Plasma ATL levels significantly increased in the 81-mg aspirin group (0.25 +/- 0.63 ng/ml, P = 0.04), with borderline increases in the 325-mg group (0.16 +/- 0.71 ng/ml) and no apparent significant changes in the 650-mg group (0.01 +/- 0.75 ng/ml, P = 0.96). When ATL and TXB2 were compared, levels changed in a statistically significant and opposite direction (P < 0.01) for all three aspirin doses. These results demonstrated that low-dose aspirin (81 mg daily) initiates production of antiinflammatory ATL opposite to the inhibition of TX. Monitoring ATL may represent a simple clinical parameter to verify an individual's vascular leukocyte antiinflammatory response with low-dose aspirin treatment. These results also emphasize the importance of cell-cell interactions in the modulation of hemostatic, thrombotic, and inflammatory processes.

Adult↗

PubMed2004

Sleep restriction does not affect orthostatic tolerance in the simulated microgravity environment.

Orthostatic intolerance (OI) is a major problem following spaceflight, and, during flight, astronauts also experience sleep restriction. We hypothesized that sleep restriction will compound the risk and severity of OI following simulated microgravity and exaggerate the renal, cardioendocrine, and cardiovascular adaptive responses to it. Nineteen healthy men were equilibrated on a constant diet, after which they underwent a tilt-stand test. They then completed 14-16 days of simulated microgravity [head-down tilt bed rest (HDTB)], followed by repeat tilt-stand test. During HDTB, 11 subjects were assigned to an 8-h sleep protocol (non-sleep restricted), and 8 were assigned to a sleep-restricted protocol with 6 h of sleep per night. During various phases, the following were performed: 24-h urine collections, hormonal measurements, and cardiovascular system identification. Development of presyncope or syncope defined OI. There was a significant decrease in time free of OI (P = 0.02) and an increase in OI occurrence (P = 0.06) after HDTB among all subjects. However, the increase in OI occurrence did not differ significantly between the two groups (P = 0.60). The two groups also experienced similar physiological changes with HDTB (initial increase in sodium excretion; increased excretion of potassium at the end of HDTB; increase in plasma renin activity secretion without a change in serum or urine aldosterone). No significant change in autonomic function or catecholamines was noted. Simulated microgravity leads to increased OI, and sleep restriction does not additively worsen OI in simulated microgravity. Furthermore, conditions of sleep restriction and nonsleep restriction are similar with respect to renal, cardioendocrine, and cardiovascular responses to simulated microgravity.

Adult↗

PubMed2004

New subcategories of class IV lupus nephritis: are there clinical, histologic, and outcome differences?

BACKGROUND: The International Society of Nephrologists and Renal Pathology Society (ISN/RPS) classification of lupus nephritis proposes a controversial subclassification of class IV lupus nephritis into IV-segmental (IV-S) and IV-global (IV-G). METHODS: A retrospective analysis of a biopsy-proven cohort of patients with lupus nephritis using the ISN/RPS classification was performed. RESULTS: The prevalence of class IV was 47% in the cohort of 70 patients with lupus nephritis. Of 33 patients with class IV lupus nephritis, 11 patients had class IV-S and 22 patients had class IV-G. There were no significant differences in age, sex, and ethnicity in the 2 groups. Greater serological activity (lower C4 level) was observed in the IV-S group, whereas serum creatinine levels and diastolic blood pressures were significantly greater in the IV-G group. Hematocrit levels, significant proteinuria (urine protein > or =3 + ), duration of systemic lupus erythematosus, and the Systemic Lupus Erythematosus Disease Activity Index were similar in the 2 groups. Histologically, combined lesions with segmental endocapillary proliferation and fibrinoid necrosis were significantly more frequent in the IV-S group. The percentage of glomeruli with cellular crescents also was greater in the IV-S group, but the difference was not significant. Wire loops were more common in the IV-G group. Transformation to IV-G was observed in 2 of 3 specimens from repeated biopsies available in the IV-S group; greater than 50% of the IV-G group had both segmental and global glomerular involvement. No significant difference was detected in outcomes in the 2 groups after average follow-ups of 38 and 55 months in the IV-S and IV-G groups, respectively. CONCLUSION: A clinical and prognostic distinction between IV-S and IV-G remains to be proven.

Adolescent↗

PubMed2004

Barriers to endoscopic colorectal cancer screening: are women different from men?

OBJECTIVES: The goals of this study were to compare women and men's understanding of screening flexible sigmoidoscopy (FS) and to identify predictors of endoscopic colorectal cancer (CRC) screening. METHODS: We mailed a 36-item questionnaire to asymptomatic patients aged 50 years or older who were scheduled for routine health assessments at a large multispecialty health-care group. Data collection included demographics, health behaviors, psychosocial factors, and CRC screening compliance. We followed participants for 1 year and assessed completion of endoscopic CRC screening. Both cross-sectional results examining previous screening and prospective results examining screening 1 year later were evaluated. RESULTS: 554 (54%) of 998 patients responded to the survey. Responses of 13 patients were excluded in the analyses due to unverifiable screening outcome. The majority of the respondents were white, and their average age was 62 years. Women reported significantly more embarrassment and fear about having FS than men. Women were more willing to consider having a FS if a female endoscopist performed the procedure. Of the 334 participants who were eligible to have endoscopic CRC screening, 53 (16%) had the procedure within a year. The odds of having the endoscopic procedures increased with the length of time the patients were under the care of their primary care providers and how strongly patients believed that one should have an FS even without symptoms. CONCLUSION: Our findings suggest some unique gender-specific attitudes and beliefs that act as potential barriers for CRC screening and further support the important role of primary care providers in facilitating timely completion of screening.

Aged↗

PubMed2004

Renal, endocrine, and cardiovascular responses to bed rest in male subjects on a constant diet.

BACKGROUND: Exposure to actual and simulated microgravity induces cardiovascular deconditioning through a variety of factors. Although the mechanisms involved remain uncertain, one involves alterations in volume-regulating systems--the hypothesis being tested in this study. To maximize our ability to detect subtle changes in the volume-regulating systems, subjects were studied on a high-average salt intake to maximally suppress these systems basally. METHODS: Fourteen healthy male subjects underwent 14-day head-down tilt bed rest (HDTB) during which a constant 200 mEq sodium, 100 mEq potassium diet was maintained. Daily 24-hour urine collection was performed; plasma renin activity, serum aldosterone, plethysmography, and cardiovascular system identification were performed during a control period (pre-HDTB) and at the end of HDTB (end HDTB). RESULTS: Sodium excretion increased initially (pre-HDTB = 182.8 +/- 10.4 mEq/total volume; early HDTB = 236.4 +/- 13.0; p = .002) and then returned to baseline values. Potassium excretion increased 4 days after the initiation of HDTB and remained elevated thereafter (pre-HDTB = 82.2 +/- 2.4/total volume; mid- to late HDTB = 89.4 +/- 2.1; p = .02). Plasma renin activity increased significantly with HDTB (pre-HDTB = 1.28 +/- 0.21 ng/mL/h; end HDTB = 1.69 +/- 0.18; p = .01), but serum aldosterone did not change. A significant decrease in autonomic responsiveness and an increase in leg compliance were observed. CONCLUSIONS: We conclude that even in the presence of a high-average salt intake diet, simulated microgravity leads to renal, cardioendocrine, and cardiovascular system alterations that likely contribute to cardiovascular deconditioning.

Adult↗

PubMed2004

Patient satisfaction with preoperative assessment in a preoperative assessment testing clinic.

UNLABELLED: Preoperative Assessment Testing Clinics (PATCs) coordinate preoperative surgical, anesthesia, nursing, and laboratory care. Although such clinics have been noted to lead to efficiencies in perioperative care, patient experience and satisfaction with PATCs has not been evaluated. We distributed a one-page questionnaire consisting of satisfaction with clinical and nonclinical providers to patients presenting to our PATC over three different time periods. Eighteen different questions had five Likert scale options that ranged from excellent (5) to poor (1). We achieved a 71.4% collection rate. The average for the subscale that indicated overall satisfaction was 4.48 +/- 0.67 and the average for the total instrument was 4.46 +/- 0.55. Although the highest scores were given for subscales describing the anesthesia, nurse, and lab, only the anesthesia subscale improved with time (P = 0.007). The subscale that involved information and communication had the highest correlation with the overall satisfaction subscale (r = 0.76; P < 0.0001). The satisfaction with the total duration of the clinic visit (3.71 +/- 1.26) was significantly less (P < 0.0001) than the satisfaction to the other items. The authors conclude that the practitioner and functional aspects of the preoperative visit have a significant impact on patient satisfaction, with information and communication versus the total amount of time spent being the most positive and negative components, respectively. IMPLICATIONS: Patient satisfaction can serve as an important indicator of the quality of preoperative care delivered in Preoperative Assessment Testing Clinics (PATC). Information and communication, both from clinical and nonclinical service providers, remain the most important positive components, and the total duration of the clinic visit represents the most negative component, of patient satisfaction in a PATC.

Anesthesia↗

PubMed2003

Diurnal variation of aldosterone and plasma renin activity: timing relation to melatonin and cortisol and consistency after prolonged bed rest.

Exposure to prolonged bed rest is known to induce changes in the renin-angiotensin-aldosterone system (RAAS) by way of posture, sodium and potassium balance, and stress, which may have serious consequences for patients. We focused on the diurnal variation of the RAAS by investigating changes in the levels of plasma renin activity (PRA) and aldosterone; for comparison to markers of the intrinsic pacemaker and to stress, we measured melatonin and cortisol. PRA, aldosterone, melatonin, and cortisol were measured hourly in 10 normal subjects with standardized sleep patterns, posture, and diet at baseline and after 11 days of prolonged bed rest conducted under a light-dark cycle. Circadian characteristics of hormone secretion patterns were estimated by multiple harmonic regression with excellent goodness-of-fit measures. Variability in the melatonin and cortisol patterns across subjects was minimal. Even for pulsatile hormones, this technique successfully estimated the acrophase, which was the salient feature. Baseline hormone peak times started with melatonin near the middle of the sleep period, followed by PRA, then aldosterone, and then cortisol around wake time. Prolonged bed rest did not induce significant changes in any timing characteristic of the secretion patterns. Baseline and prolonged bed rest peak times for melatonin and cortisol and amplitude characteristics for all hormones were highly correlated, indicating consistency within individuals. These data provide strong evidence that prolonged bed rest of 11 days' duration does not disrupt either the timing characteristics of the RAAS or the intrinsic pacemaker.

Adult↗

PubMed2003

Development of circulatory-renal limitations to angiotensin-converting enzyme inhibitors identifies patients with severe heart failure and early mortality.

OBJECTIVES: This study examined the hypothesis that patients who develop angiotensin-converting enzyme inhibitor intolerance attributable to circulatory-renal limitations (CRLimit) have more severe underlying disease and worse outcome. BACKGROUND: Although the renin-angiotensin system contributes to the progression of heart failure (HF), it also supports the failing circulation. Patients with the most severe disease may not tolerate inhibition of this system. METHODS: Consecutive inpatient admissions to the cardiomyopathy service of the Brigham and Women's Hospital between 2000 and 2002 were reviewed retrospectively for initial profiles, discharge medications, and documented reasons for discontinuation of angiotensin-converting enzyme inhibitors. Outcomes of death and transplantation were determined. RESULTS: Of the 259 patients, 86 were not on an angiotensin-converting enzyme inhibitor at discharge. Circulatory-renal limitations of symptomatic hypotension, progressive renal dysfunction, or hyperkalemia were documented in 60 patients (23%); other adverse effects, including cough, in 24 patients; and absent reasons in 2 patients. Compared with patients on angiotensin-converting enzyme inhibitors, patients with CRLimit were older (60 vs. 55 years; p = 0.006), with longer history of HF (5 vs. 2 years; p = 0.009), lower systolic blood pressure (104 vs. 110 mm Hg; p = 0.05), lower sodium (135 vs. 138 mEql/l; p = 0.002), and higher initial creatinine (2.5 vs. 1.2 mg/dl; p = 0.0001). Mortality was 57% in patients with CRLimit and 22% in the patients on angiotensin-converting enzyme inhibitors during a median 8.5-month follow-up (p = 0.0001). CONCLUSIONS: Development of CRLimit to angiotensin-converting enzyme inhibitor intolerance identifies patients with severe disease who are likely to die during the next year. New treatment strategies should be targeted to this population.

Adrenergic beta-Antagonists↗

PubMed2003

Natural history of benign solid and cystic thyroid nodules.

BACKGROUND: Thyroid nodules are common and most often benign. The natural history of benign thyroid nodules, however, is unclear. OBJECTIVE: To determine the natural history of cytologically benign thyroid nodules using ultrasonography. DESIGN: Retrospective case series. SETTING: Single tertiary care clinic. PARTICIPANTS: All patients referred to the Brigham and Women's Hospital Thyroid Nodule Clinic, Boston, Massachusetts, who had benign cytologic results on ultrasonography-guided fine-needle aspiration of a thyroid nodule between 1995 and 2000 and returned for a requested follow-up examination 1 month to 5 years later. MEASUREMENTS: Nodule dimensions were measured at both visits, and growth was defined as an increase in calculated volume of 15% or greater. These results were correlated with the time between examinations, age, sex, baseline serum thyroid-stimulating hormone concentration, and cystic content of each nodule. RESULTS: Nodule volume increased over time (P < 0.001). The estimated proportion of nodules with an increase in volume of 15% or greater after 5 years was 89%. Nodules with greater cystic content were less likely to grow than solid nodules (P = 0.01). Seventy-four of the 330 nodules were reaspirated on the second visit. Despite an average increase in volume of 69%, only 1 of 74 reaspirated nodules was malignant. CONCLUSION: Most solid, benign thyroid nodules grow. Therefore, an increase in nodule volume alone is not a reliable predictor of malignancy.

Biopsy, Needle↗

PubMed2003

Identification of serum soluble ST2 receptor as a novel heart failure biomarker.

BACKGROUND: Using genomic technology, we previously identified an interleukin-1 receptor family member, ST2, as a gene markedly induced by mechanical strain in cardiac myocytes. The soluble receptor form of ST2 is secreted and detectable in human serum. This study tested the hypothesis that soluble ST2 levels in the serum of patients with severe chronic heart failure are increased in patients with neurohormonal activation. METHODS AND RESULTS: Serum samples, clinical variables, and neurohormone levels from the PRAISE-2 heart failure trial (NYHA functional class III-IV; end point, mortality or transplantation) were analyzed. ST2 serum measurements were performed with ELISA on samples from 161 patients obtained at trial enrollment and from 139 of the same patients obtained 2 weeks after trial enrollment. Baseline ST2 levels were correlated with baseline B-type natriuretic peptide (BNP) levels (r=0.36, P<0.0001), baseline proatrial natriuretic peptide (ProANP) levels (r=0.36, P<0.0001), and baseline norepinephrine levels (r=0.39, P<0.0001). The change in ST2 was significant as a univariate predictor of subsequent mortality or transplantation (P=0.048), as was baseline BNP (P<0.0001) and baseline ProANP (P<0.0001). In multivariate models including BNP and ProANP, the change in ST2 remained significant as a predictor of mortality or transplantation independent of BNP and ProANP. CONCLUSIONS: Serum soluble ST2 is a novel biomarker for neurohormonal activation in patients with heart failure. In patients with severe chronic NYHA class III to IV heart failure, the change in ST2 levels is an independent predictor of subsequent mortality or transplantation.

Adolescent↗