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Biomedical subjects

S Brady

Publications and source records attributed to S Brady.

At least 19 recordsLinked to original sources
PubMed1999

Silent myocardial ischemia and microalbuminuria in asymptomatic subjects with non-insulin-dependent diabetes mellitus.

Microalbuminuria is an increase in urinary albumin not detected by conventional dipstick testing and is present in 20% of patients with non-insulin-dependent diabetes mellitus (NIDDM). Mortality in NIDDM patients with microalbuminuria is 60% at 8 years and is mainly due to cardiovascular disease. Because many deaths occur without warning symptoms, we have compared the prevalence and severity of silent myocardial ischemia in asymptomatic NIDDM patients with and without microalbuminuria. We have performed a cross-sectional, case-control study of asymptomatic NIDDM patients attending hospital diabetes clinics. Forty-three patients with microalbuminuria were matched for age, gender, diabetes duration, and smoking status with 43 normoalbuminuric patients. A symptom-limited exercise stress test was performed and reported blind to patient status. The degree of electrocardiographic ST-segment depression, exercise time, work performed, and maximum heart rate with exercise were recorded. Patients with microalbuminuria had a higher prevalence of ischemic response (>1 mm ST depression) (65% vs 40%, p = 0.016), reduced total exercise time (5 vs 7 minutes, p <0.001), reduced work (6 vs 8 METs, p <0.001), and reduced age-predicted maximum heart rate (94% vs 101%, p = 0.004). In multiple logistic regression, albumin excretion rate was shown to be the strongest independent predictor of ischemic response (p = 0.03). Silent myocardial ischemia is common in asymptomatic NIDDM patients but is more common in those with microalbuminuria. In these subjects, the higher prevalence of ischemic response at low workloads suggests a higher probability of future coronary events, and possibly a higher probability of potentially treatable coronary artery disease.

Aged↗
PubMed1998

Autonomic neuropathy in asymptomatic subjects with non-insulin-dependent diabetes mellitus and microalbuminuria.

Patients with non-insulin-dependent diabetes mellitus (NIDDM) and microalbuminuria (MA) are at increased risk of early death. In NIDDM patients without evidence of heart disease, we examined the links between MA and autonomic neuropathy (AN) and reduced heart rate variability (HRV), both of which have been linked to a poor prognosis. We have studied 43 asymptomatic NIDDM patients with MA and have matched them with 43 normoalbuminuric patients for age, gender, diabetes duration, and smoking status. AN was assessed by heart rate changes to deep breathing, Valsalva, and posture and blood pressure changes to posture and hand grip. Twenty-four hour Holter monitoring was used to evaluate HRV. Patients with MA showed evidence of AN and reduced HRV when compared with normoalbuminuric patients. In multivariate analysis, with measures of AN and HRV as outcome variables, Log albumin excretion rate was a significant independent predictor but stronger predictors were the presence of diabetic retinopathy, age, body mass index, claudication, alcohol consumption, and calcium channel blocker use. The presence of MA is linked to AN and reduced HRV in asymptomatic NIDDM patients. The nature of the relationship is complex, involving multiple relationships with other clinical parameters.

Aged↗
PubMed1998

Exercise response of the recipient atrial remnant after orthotopic cardiac transplantation: implications for recipient atrial triggered pacing.

The assumption that the recipient atrial remnant in the cardiac transplant recipient is normal has led to the suggestion that it is an appropriate trigger for permanent pacing in transplant recipients who need pacing or to restore chronotropic competence and/or mechanical synchrony of the composite atrium. We examined the chronotropic response to exercise in 12 orthotopic cardiac transplant recipients (mean age 49 years) at a mean time of 17 months posttransplantation. Recipient and donor atrial rates were noted and compared and chronotropic competence determined. Two of 12 recipient atrial remnants were in atrial fibrillation. Only six of the remaining 10 recipient atria exhibited chronotropic competence. Seven of 10 recipient atria had rates higher than that of the donor. Only four of ten recipient atria in sinus rhythm satisfied both criteria. Two of these had abnormally high atrial responses early into exercise. Of the remaining two, only one recipient atrial remnant demonstrated a > or = 20% increase in heart rate above that of the donor at peak exercise. Hence only 1 of 12 (8.3%) transplant recipients potentially could benefit from recipient atrial triggered pacing. While recipient atrial triggered pacing is an attractive theoretical concept for restoring chronotropic competence following orthotopic cardiac transplantation, it may rarely be practical because the recipient atrial remnant displays rhythm abnormalities, chronotropic incompetence, and abnormalities in its exercise response.

Atrial Function↗
PubMed1997

Speech perception deficits in poor readers: auditory processing or phonological coding?

Poor readers are inferior to normal-reading peers in aspects of speech perception. Two hypotheses have been proposed to account for their deficits: (i) a speech-specific failure in phonological representation and (ii) a general deficit in auditory "temporal processing," such that they cannot easily perceive the rapid spectral changes of formant transitions at the onset of stop-vowel syllables. To test these hypotheses, two groups of second-grade children (20 "good readers," 20 "poor readers"), matched for age and intelligence, were selected to differ significantly on a /ba/-/da/ temporal order judgment (TOJ) task, said to be diagnostic of a temporal processing deficit. Three experiments then showed that the groups did not differ in: (i) TOJ when /ba/ and /da/ were paired with more easily discriminated syllables (/ba/-/sa/, /da/-/fa/); (ii) discriminating nonspeech sine wave analogs of the second and third formants of /ba/ and /da/; (iii) sensitivity to brief transitional cues varying along a synthetic speech continuum. Thus, poor readers' difficulties with /ba/-/da/ reflected perceptual confusion between phonetically similar, though phonologically contrastive, syllables rather than difficulty in perceiving rapid spectral changes. The results are consistent with a speech-specific, not a general auditory, deficit.

Child↗
PubMed1997

Stereotactic biopsy procedures for brain tumor diagnosis.

Stereotactic biopsy procedures, in which a computer-based, three-dimensional-image-guided system accurately locates patients' brain tumors, are relatively new diagnostic methods. Complications from stereotactic biopsy procedures are minimal compared with open craniotomy procedures because they are performed with local anesthesia. Perioperative nurses should have knowledge of and be trained in stereotactic biopsy procedures to ensure optimal care for patients undergoing these procedures.

Aged↗
PubMed1997

Composite pheochromocytoma/ganglioneuroma of the adrenal gland associated with multiple endocrine neoplasia 2A: case report with immunohistochemical analysis.

We report a case of composite pheochromocytoma/ganglioneuroma arising in a background of diffuse and nodular medullary hyperplasia in the adrenal gland of a 34-year-old man with multiple endocrine neoplasia 2a (MEN 2a). Cells were histologically classified as chromaffin or chromaffin-like (small typical-appearing pheochromocytoma cells), neuron-like (possessing ganglion cell morphology), and intermediate. We speculate that these cell types may represent a spectrum of differentiation of a neoplastic clone, with the intermediate cells representing a transitional stage between chromaffin cells and neurons. All three cell types in the composite tumor and all chromaffin cells in both nodular and nonnodular areas of the remaining medulla were strongly immunoreactive for tyrosine hydroxylase, the rate-limiting enzyme in catecholamine synthesis. In contrast, neuron-like cells (and to a variable extent intermediate cells) displayed selective loss of expression of phenylethanolamine-N-methyltransferase (PNMT), the enzyme that synthesizes epinephrine. Proliferative activity of the composite tumor and both the nodular and nonnodular medulla was studied by staining for the endogenous cell proliferation antigen Ki-67, using monoclonal antibody MIB-1. MIB-1 labeling was highest in Schwann cell areas of the composite tumor, followed by chromaffin-like cells in the composite tumor and in the separate nodules. Labeling was absent in neuron-like cells, consistent with the cells' postulated status as terminally differentiated derivatives of a chromaffin cell precursor, and was highly variable in nonnodular areas of the medulla. The latter observation suggests topographical variation in signals that drive chromaffin cell proliferation in MEN.

Adrenal Gland Neoplasms↗
PubMed1997

An STS-based radiation hybrid map of the human genome.

We have constructed a physical map of the human genome by using a panel of 83 whole genome radiation hybrids (the Stanford G3 panel) in conjunction with 10,478 sequence-tagged sites (STSs) derived from random genomic DNA sequences, previously mapped genetic markers, and expressed sequences. Of these STSs, 5049 are framework markers that fall into 1766 high-confidence bins. An additional 945 STSs are indistinguishable in their map location from one or more of the framework markers. These 5994 mapped STSs have an average spacing of 500 kb. An additional 4484 STSs are positioned with respect to the framework markers. Comparison of the orders of markers on this map with orders derived from independent meiotic and YAC STS-content maps indicates that the error rate in defining high-confidence bins is < 5%. Analysis of 322 random cDNAs indicates that the map covers the vast majority of the human genome. This STS-based radiation hybrid map of the human genome brings us one step closer to the goal of a physical map containing 30,000 unique ordered landmarks with an average marker spacing of 100 kb.

Animals↗
PubMed1996

A gene map of the human genome.

The human genome is thought to harbor 50,000 to 100,000 genes, of which about half have been sampled to date in the form of expressed sequence tags. An international consortium was organized to develop and map gene-based sequence tagged site markers on a set of two radiation hybrid panels and a yeast artificial chromosome library. More than 16,000 human genes have been mapped relative to a framework map that contains about 1000 polymorphic genetic markers. The gene map unifies the existing genetic and physical maps with the nucleotide and protein sequence databases in a fashion that should speed the discovery of genes underlying inherited human disease. The integrated resource is available through a site on the World Wide Web at http://www.ncbi.nlm.nih.gov/SCIENCE96/.

Amino Acid Sequence↗
PubMed1996

Dual diagnosis: a treatment model for substance abuse and major mental illness.

The treatment of "dual diagnosis", co-occurring substance abuse and mental illness, calls for addressing two serious and often confounding problems. The authors introduce an expanded version of the transtheoretical model of change as formulated by J.O. Prochaska and C.C. DiClemente, and suggest that this new version offers a pragmatic approach to the conceptualization and treatment of dual diagnosis. The potential utility of the treatment model is presented through the authors' experiences in working with inner-city, chronic mentally ill individuals with substance abuse problems. Practical guidelines for dual diagnosis group therapy are discussed.

Chronic Disease↗
PubMed1996

Vasopressin release during orthostatic hypotension after cardiac transplantation.

At the time of cardiac transplantation all nerves from the donor ventricles are cut. These nerves may regrow, but there is no method of measuring any regrowth. Arginine vasopressin (AVP) release was studied during hypotension induced by head-up tilt and lower body negative pressure (LBNP) in transplant recipients and in normal controls. Subjects were tilted to 60 degrees for up to 60 min or until symptomatic. Lower body negative pressure (40 mmHg) was applied for 10 min after 30 min rest. Seven of 17 transplant recipients and 11 of 12 controls became symptomatic during tilt testing, and 9 of 12 controls and 9 of 17 transplant recipients became symptomatic after 10 min of LBNP. Symptoms during tilt did not predict symptoms during LBNP. Resting AVP levels were similar but osmolality was greater in transplant recipients. Resting haematocrit was reduced, and atrial natriuretic peptide increased in transplant recipients, suggesting increased plasma volume. In symptomatic subjects, changes in humoral concentrations were similar when compared between transplant recipients and normals, except that the rise in AVP at the time of symptoms was reduced in transplant recipients, with a comparable drop in blood pressure consistent with persistent cardiac afferent denervation in a subset of transplant recipients.

Adult↗
PubMed1996

Sepsis increases endocytosis of endotoxin into hepatocytes.

BACKGROUND: Chylomicrons bind endotoxins and accelerate their clearance from plasma to the liver. This results in reduced mortality from septic shock in a rodent model. We hypothesized that the clearance of the LPS-chylomicron (LPS-CM) complex by hepatocytes is due to receptor-mediated endocytosis and that sepsis up-regulates this process. METHODS: Three groups of Sprague-Dawley rats; (1) control; (2) pretreated with 10 micrograms/kg LPS 24 hours before treatment; and (3) pretreated with 17-alpha-ethinyl estradiol (EE, 5 mg/kg subcutaneously for 3 days), were infused with labeled I125-LPS alone or with I125-LPS bound to chylomicron. Livers were removed 2.5, 15, and 30 minutes after LPS injection, and hepatic endosomes were isolated from the liver homogenates by serial ultracentrifugation in sucrose gradients. RESULTS: The injection of I125-LPS-CM complexes resulted in higher levels of endosomal I125-LPS in all groups, as compared with I125-LPS alone. In addition, the endosomal uptake of I125-LPS was markedly increased by both LPS and EE pretreatments. CONCLUSIONS: These data strongly suggest a primary role for receptor-mediated endocytosis in the increased clearance of LPS when bound to chylomicron. In addition, exposure to LPS appears to increase the accumulation of LPS in endosomes by a mechanism similar to that of EE, which is known to up-regulate receptor-mediated lipoprotein uptake. This endogenous pathway for the catabolism of endotoxins may provide a teleological explanation for the hypertriglyceridemia observed during sepsis.

Animals↗
PubMed1996

Exercise response after cardiac transplantation: correlation with sympathetic reinnervation.

OBJECTIVE: To investigate the relation between sympathetic efferent reinnervation and chronotropic competence during exercise testing after cardiac transplantation. PATIENTS: Twenty five long-term cardiac transplant recipients and 11 normal controls. SETTING: Regional cardiothoracic centre. METHODS: Intracoronary tyramine was given to the transplant recipients and the per cent heart rate change measured. Exercise tests were performed in patients and controls according to the chronotropic assessment exercise protocol, and the per cent heart rate reserve measured at peak exercise and 6 min afterwards to estimate the recovery rate. RESULTS: The mean (SD) percentage heart rate change after intracoronary tyramine was 15.7 (15.4). Heart rate reserve achieved at peak exercise was 68.3 (20.6)% compared with 102.7 (9.3)% in the controls (P < 0.001). Heart rate recovery at 6 min was 41.7 (20.1)% compared with 79.5 (9.0)% in the controls (P < 0.001). Total workload was 69.0 (33.0) METS.min compared with 117.2 (41.9) METS.min in the controls (P < 0.01). There was a positive correlation between heart rate reserve achieved at peak exercise and response to tyramine (r = 0.66, P < 0.01), between heart rate recovery and response to tyramine (r = 0.69, P < 0.001), and between total workload and response to tyramine (r = 0.63, P = 0.04). CONCLUSION: Functional sympathetic efferent reinnervation of the sinus node occurred in some patients after transplantation, and was associated with improved heart rate response during and recovery after exercise, as well as with increased total workload.

Adult↗
PubMed1994

Effect of the 39-kDa receptor-associated protein on the hepatic uptake and endocytosis of chylomicron remnants and low density lipoproteins in the rat.

The low density lipoprotein (LDL) receptor-related protein, which serves as the cell surface receptor for several proteins including alpha 2-macroglobulin-protease complexes, has been proposed to be a candidate hepatocytic receptor for chylomicron remnants through its recognition of apolipoprotein E. We have studied the effect of two ligands for this receptor, activated alpha 2-macroglobulin and the recently described 39-kDa protein that copurifies with the LDL receptor-related protein (receptor-associated protein), on the uptake and endocytosis of chylomicrons in intact rats and in isolated, perfused rat livers. Both of these ligands were rapidly taken up and endocytosed into the liver of rats. Chylomicrons from normal rats were injected in vivo and chylomicrons from estradiol-treated rats that were enriched in apolipoprotein E were added to liver perfusates. Prior administration of amounts of activated alpha 2-macroglobulin that saturated hepatic uptake mechanisms did not inhibit hepatic uptake or endocytosis of endogenously labeled cholesteryl esters of chylomicron particles in vivo or in perfused livers over a period of 15 min. By contrast, prior administration of saturating amounts of the receptor-associated protein (expressed in bacteria as a fusion protein with glutathione S-transferase) reduced hepatic uptake by about 30% and virtually abolished endocytosis. The receptor-associated protein inhibited hepatic uptake of human LDL in vivo by 70% and endocytosis by 81%. Our results show that receptor-associated protein-sensitive processes predominate in the overall pathways by which chylomicron remnants are endocytosed by rat liver. Furthermore, they show that the receptor-associated protein binds to and inhibits the function of the LDL receptor as well as the LDL receptor-related protein.

Animals↗
PubMed1994

Physical progress and residual impairment quantification after functional restoration. Part II: Isokinetic trunk strength.

The current study evaluated human skeletal muscle performance through isokinetic trunk strength testing before and after a comprehensive functional restoration program for a group of 191 chronic low back pain (CLBP) patients. Four groups of patients were identified: 1) postdiscectomy men (n = 26); 2) unoperated men (n = 90); 3) postdiscectomy women (n = 17); and 4) unoperated women (n = 58). Patient test scores were expressed as work normalized to body weight at 60 and 150 degrees/second. The absolute scores were also expressed as "percent normal" relative to a population average normative database (specific to age and gender). An "effort factor" based on the average points variance (APV) of computer-generated curves was also calculated. Results demonstrated improvements in trunk strength measures at all speeds in flexion and extension for all groups. All groups also demonstrated a decrease in APV mean scores after functional restoration, with only 1 of 191 patients remaining in the POOR effort (strength inhibited) group after treatment. The postoperative men showed the greatest effort improvement, with APV scores in the "good" range increasing from 57% to 91% of the group over the course of treatment. There was virtually no difference in gender-specific trunk strength scores between postdiscectomy and unoperated patients, either at program entry or program discharge. However, compared with the normative database of program completion, even in the presence of good effort, persistent residual (and, possibly, permanent) strength impairment was identified.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗