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Biomedical subjects

A Kennedy

Publications and source records attributed to A Kennedy.

At least 109 records · Page 6Linked to original sources
PubMed1997

A prospective randomized study of glutamine-enriched parenteral compared with enteral feeding in postoperative patients.

Plasma amino acids were measured in 17 postoperative subjects randomly assigned to receive for > or = 5 d tube feeding or total parenteral nutrition (TPN) that had identical energy, nitrogen, and glutamine contents. Subjects required gastric or pancreatic surgery for malignancy and were well-matched for age and body mass index. Tube feeding or TPN began on postoperative day 1 and advanced in daily 25% increments to meet goals of 105 kJ . kg body wt-1 . d-1, 1.5 g protein . kg body wt-1 . d-1, and 0.3 g glutamine . kg body wt-1 . d-1. Delivered energy, nitrogen, and glutamine were closely matched on day 4. Nitrogen balance and plasma proteins did not differ significantly between feeding groups. Total indispensable amino acids, branched-chain amino acids, and glutamine declined 25% on postoperative day 1 compared with preoperative day 0. Indispensable and branched-chain amino acid concentrations were restored with 5 d of either tube feeding or TPN. Glutamine concentrations did not differ significantly by feeding group, though a trend suggested that glutamine recovered more slowly in the tube-fed than in the TPN-fed subjects. Plasma amino acids otherwise reflected formula composition with ratios of valine to leucine of 1.24 and 3.69 mumol/L in subjects receiving 5 d of tube feeding or TPN, respectively. These findings suggest that glutamine-enriched tube feeding and TPN can result in similar profiles for most plasma amino acids at carefully matched doses.

Adolescent↗
PubMed1997

Clinical pathways in acoustic tumor management.

Clinical pathways are tools for cost containment and quality improvement in the managed care environment. This report describes our experience with developing and implementing a clinical pathway for acoustic neuroma surgery. Intensive care unit bed days and inpatient hospitalization days for cerebellopontine angle surgery significantly decreased during the months that the pathway was developed, and the incidence of complications was unchanged after adoption of the algorithm. We conclude that with joint neurootology and neurosurgery leadership clinical pathways can be a safe, cost-effective, and clinically useful technique in acoustic neuroma surgery in a managed care setting. As this management scheme evolves, surgeons must take the leadership to ensure that decisions are based on clinically relevant parameters.

Algorithms↗
PubMed1997

Exercise and heart disease: cardiac findings in fatal cycle accidents.

BACKGROUND: Regular cyclists have been found to have a lower incidence of coronary events (CHD) than the general public. Non-invasive studies have found that competitive cyclists develop a cardiac hypertrophy that is physiological and reversible. METHODS: To obtain pathological support for these observations, the postmortem findings of 32 cyclists killed in accidents have been compared with those in a control group of 32 other road traffic accidents, which were matched with the cyclists by sex, age, and year of death. FINDINGS: Large myocardial scars and complete blockage of a coronary artery were only found in the controls; serious stenoses of coronary arteries (> 50%) were found in eight controls but in only one of the cyclists. Of the cyclists, 25 had normal coronary arteries as compared with 14 of the controls. The mean age of the cyclists with evidence of CHD was greater than that of similarly affected controls. The heart weights of the two groups were almost the same but heart weight varied with the degree of CHD. The heart weight of the healthy cyclists (389 g) was greater than that of the healthy controls (371 g) but this was not statistically significant. INTERPRETATION: The results are in keeping with the concept that regular exercise provides some protection from the development of CHD and that cycling may be a valuable form of exercise in this respect. This may be of importance as the number of physically active occupations declines.

Accidents, Traffic↗
PubMed1997

The metabolic significance of leptin in humans: gender-based differences in relationship to adiposity, insulin sensitivity, and energy expenditure.

Leptin is an adipocyte-derived hormone that interacts with a putative receptor(s) in the hypothalamus to regulate body weight. The relationship of leptin to metabolic abnormalities associated with obesity together with hormonal and substrate regulation of leptin have not been extensively studied. Therefore, 116 subjects (62 men and 54 women) with a wide range of body weight [body mass index (BMI), 17-54 kg/m2] were characterized on a metabolic ward with regard to body composition, glucose intolerance, insulin sensitivity, energy expenditure, substrate utilization, and blood pressure. Eighty-five of the subjects had normal glucose tolerance (50 men and 35 women), and 31 had noninsulin-dependent diabetes mellitus (12 men and 19 women). In both men and women, fasting leptin levels were highly correlated with BMI (r = 0.87 and r = 0.88, respectively) and percent body fat (r = 0.82 and r = 0.88, respectively; all P < 0.0001). However, men exhibited lower leptin levels at any given measure of obesity. Compared with those in men, leptin levels rose 3.4-fold more rapidly as a function of BMI in women [leptin = 1.815 (BMI)-31.103 in women; leptin = 0.534 (BMI)-8.437 in men] and 3.2 times more rapidly as a function of body fat [leptin = 1.293 (% body fat)-24.817 in women; leptin = 0.402 (% body fat)-3.087 in men]. Hyperleptinemia was associated with insulin resistance (r = -0.57; P < 0.0001) and high waist to hip ratio (r = 0.75; P < 0.0001) only in men. On the other hand, during the hyperinsulinemic euglycemic clamp studies, hyperinsulinemia acutely increased leptin concentrations (20%) only in women. There was no correlation noted between fasting leptin levels and either resting energy expenditure or insulin-induced thermogenesis in men or women (P = NS). In stepwise and multiple regression models with leptin as the dependent variable, noninsulin-dependent diabetes mellitus did not enter the equations at a statistically significant level. The data indicate that there are important gender-based differences in the regulation and action of leptin in humans. Serum leptin levels increase with progressive obesity in both men and women. However, for any given measure of obesity, leptin levels are higher in women than in men, consistent with a state of relative leptin resistance. These findings have important implications regarding differences in body composition in men and women. The observation that serum leptin is not related to energy expenditure rates suggests that leptin regulates body fat predominantly by altering eating behavior rather than calorigenesis.

Adipose Tissue↗
PubMed1997

Postmortem fetal MR imaging: comparison with findings at autopsy.

OBJECTIVE: The purpose of this study was to prospectively compare findings from postmortem fetal MR imaging with findings at autopsy. SUBJECTS AND METHODS: Twenty-six fetuses were imaged on a 1.5-T MR scanner using two-dimensional and high-resolution three-dimensional fast spin-echo techniques immediately before autopsy. The MR images were reviewed independently by three radiologists who evaluated then for major and minor malformations. These findings were then compared with those at autopsy. RESULTS: The 26 subjects had 47 major and 11 minor malformations. All three radiologists correctly identified 37 of the major malformations on the MR images (detection rate, 79%), and at least one of the three reviewers correctly identified 43 of the abnormalities (detection rate, 91%). Only one of the 11 minor anomalies was identified by any reviewer. Reviewers made six false-positive diagnoses. In two cases, both with major CNS malformations, MR imaging was superior to autopsy in defining in situ relationships. CONCLUSION: Although autopsy remains the study of choice for evaluating causes of fetal death, MR imaging is an excellent alternative when autopsy is refused. Additionally, MR imaging may be a valuable adjunct to autopsy for fetuses with CNS anomalies.

Abnormalities, Multiple↗
PubMed1997

Muscle Rad expression and human metabolism: potential role of the novel Ras-related GTPase in energy expenditure and body composition.

Ras associated with diabetes (Rad), a new ras-related GTPase, was recently identified by subtractive cloning as an mRNA in skeletal muscle that is overexpressed in NIDDM. To better understand its metabolic significance, we measured skeletal muscle Rad expression in well-characterized insulin sensitive (IS) and insulin resistant (IR) subjects with normal glucose tolerance and in untreated NIDDM patients. We found no differences in expression of Rad mRNA levels among IS, IR, and NIDDM groups using a ribonuclease protection assay (0.22 +/- 0.06, 0.13 +/- 0.01, and 0.16 +/- 0.02 relative units, respectively; NS) and no differences in Rad protein expression using a specific anti-peptide Rad antibody (1.05 +/- 0.18, 1.14 +/- 0.08, and 1.08 +/- 0.21 units/mg protein, respectively; NS). However, Rad protein levels were positively correlated with BMI (r = 0.43, P = 0.03) and percentage body fat (r = 0.55, P < 0.005), two independent measures of obesity, and negatively correlated with resting metabolic rate (r = 0.49, P = 0.01). In multiple regression analyses, percentage body fat and resting metabolic rate independently accounted for 30 and 10% of individual variability in muscle Rad protein expression. In conclusion, Rad expression in skeletal muscle is not altered as a function of insulin resistance or NIDDM in humans. However, these data, for the first time, implicate a role for Rad in regulating body composition and energy expenditure and provide a framework for studies designed to elucidate Rad's cellular functions.

Absorptiometry, Photon↗
PubMed1997

Vascular endothelial growth factor is present in glial cells of the retina and optic nerve of human subjects with nonproliferative diabetic retinopathy.

PURPOSE: To determine whether vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), which have been implicated in the development of retinal and choroidal neovascularization, are present in the retinas and optic nerves of patients with diabetes before proliferative retinopathy appears. METHODS: Light microscopic immunocytochemistry using antibodies to VEGF, bFGF, vimentin, glial fibrillary acidic protein (GFAP), and factor VIII on frozen sections from eyes of patients with diabetes without proliferative retinopathy, eyes of patients without diabetes and without known ocular disease, and eyes with disciform age-related macular degeneration (ARMD). Retinal vascular digest preparations to evaluate microvascular abnormalities. RESULTS: Based on morphology and on GFAP and vimentin immunopositivity, retinas from all subjects with diabetes immunostained strongly to VEGF in elongated processes that appeared to be Müller cells. Glial cells within septa surrounding axons in the anterior optic nerve also immunostained for VEGF, as did endothelial cells of some posterior retinal blood vessels and some retinal pigment epithelial cells. Retinas from eyes with disciform ARMD immunostained for VEGF, though less extensively than did those of subjects with diabetes. Retinas and optic nerves from subjects without ocular disease were VEGF negative. Basic fibroblast growth factor was expressed minimally in the inner retinal layers of subjects with and without diabetes, but it was substantial in the photoreceptor layer of all eyes. Vascular endothelial growth factor immunopositivity was present in eyes with no, or little, retinal vascular anatomic abnormality in digest preparations. CONCLUSIONS: Vascular endothelial growth factor expression precedes retinal neovascularization in the retinas and the optic nerves of humans with diabetes. Its localization to glial cells of the inner retina and the anterior optic nerve suggests a relationship to neovascularization in these sites. That VEGF immunopositivity may occur when there is no anatomic evidence of retinal nonperfusion and little likelihood of retinal neovascularization suggests the possibility that ischemia may not be the sole stimulus for VEGF expression.

Aged↗
PubMed1997

An ELISA for measuring tumour necrosis factor alpha in rat plasma.

Tumour necrosis factor (TNF) is a cytokine with multiple biological activities which plays a pivotal role in the response of the body to infection. TNF is secreted in the the monomeric form and associates to yield a biologically active oligomeric molecule. Bioactive TNF can be measured in plasma using cytotoxic assays which employ the murine cell-lines L929 or WEHI 164 clone 13. However, it has become clear that inactive TNF also circulates in vivo, which is not detected by bioassay. These inactive forms may play an important role in the regulation of TNF activity. The rat is often used as a model for the study of acute infection and its systemic effects. Our aim was to develop an ELISA for rat TNF which would provide a convenient and cost effective method of assay. The assay employs two commercially available antibodies raised against recombinant murine TNF (rMuTNF) which exhibit cross-reactivity with rat TNF. The lower limit of detection for this assay was determined to be 39.0 pg/ml rMuTNF. The inter and intra-assay coefficients of variation were < 12.0%. Specificity of the assay was shown by the high degree of parallelism obtained between rMuTNF and commercially available rRatTNF. The assay described measures rat TNF in both plasma and tissue culture supernatant. The measurement of plasma concentrations of TNF using both the ELISA and bioassay may help elucidate more fully the biological importance of TNF.

Animals↗
PubMed1997

A comparison of the cytology of endomyocardial biopsy washings from heart transplants with biopsy histologic study and peripheral blood lymphocyte counts.

Cytospin preparations of endomyocardial biopsy washings were examined on 117 occasions from 13 heart transplant recipients and categorized according to the pattern of cell types observed. Twenty-nine percent of samples were acellular, a further 10% too bloodstained for analysis, and 61% were cellular. Eight lymphocytic samples were found and in all cases there was at least grade 1B rejection (four grade 1B, three grade 2, and one grade 3A) on histologic study. However, histologic study showed at least 1B rejection in 48% of cases when cytospins showed mixed inflammatory cells, 33% of cases when cytospins were histiocytic and in 35% when cytospins were bloodstained or acellular. Furthermore 16 of these rejection episodes with nonlymphocytic cytospins were grade 2. Although the recovery of a lymphocytic cytospin was specific for rejection, the sensitivity of the test was poor. Even when the sample is adequate, this method of biopsy washings will predict only one third of cases of significant acute rejection (grade 2 or worse). The large proportion of unsuitable samples also severely limits the utility of endomyocardial biopsy washings for the diagnosis of rejection. Histiocytic cytospins were seen in 63% of samples when previous biopsy sites were reported on histologic study and also in all three samples when histologic study showed ischemic injury. A mixed inflammatory cell pattern was seen to a lesser extent (31% of samples) in relation to previous biopsy sites. High peripheral blood lymphocyte counts were found when endomyocardial biopsy washings were lymphocytic or mixed inflammatory and also when histologic study showed endocardial lymphocytic infiltration (Quilty effect).

Biopsy↗
PubMed1997

Carboplatin plus paclitaxel in the treatment of gynecologic malignancies: the Cleveland Clinic experience.

To examine the toxicity profile and antineoplastic activity of carboplatin (area under the concentration-time curve of 4 to 7.5) plus 3-hour infusional paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) (135 or 175 mg/m2) in women with advanced gynecologic malignancies, we retrospectively reviewed the experience of the Gynecologic Cancer Program at The Cleveland Clinic with this combination chemotherapy regimen. To date, 92 patients (median age, 67 years) have received a total of 460 courses (median number per patient, six) of this two-drug combination. The initial paclitaxel dose was 175 mg/m2 and the carboplatin area under the concentration-time curve was > or = 5 in 72% and 73% of patients, respectively. The major toxicity was neutropenia (grade 4 in 9% of patients), resulting in two febrile episodes and a single septic death. Grade 4 thrombocytopenia and grade 3 peripheral neuropathy were noted in one and two patients, respectively. Twelve patients (13%) experienced at least one episode of paclitaxel-associated hypersensitivity, but all were able to continue with the treatment program. Of the 62 patients with ovarian cancer or primary peritoneal carcinoma with carbohydrate antigen-125 levels > or = 60 U/mL before the initiation of chemotherapy, 74% exhibited a > or = 90% decline in the tumor marker following treatment. We conclude that the combination of carboplatin and 3-hour infusional paclitaxel can be administered in the outpatient setting with a highly acceptable toxicity profile and with major activity in patients with ovarian cancer and primary carcinoma of the peritoneum.

Adult↗
PubMed1996

Surgical research.

Explore the source record for details and available documents.

General Surgery↗
PubMed1996

Control of carboplatin-induced emesis with a fixed low dose of granisetron (0.5 mg) plus dexamethasone.

In an effort to develop a cost-effective antiemetic regimen for carboplatin-based chemotherapy, we examined a fixed (0.5 mg) low dose of granisetron (a new 5-HT3 (serotonin) antagonist) plus dexamethasone (20 mg) in 23 patients with gynecologic malignancies receiving this antineoplastic drug. Nineteen (83%) patients experienced complete control of acute emesis (nausea and vomiting) while 22 (96%) individuals demonstrated complete or major control (< or = 2 episodes of vomiting, < or = 5 episodes of retching, minimal interference with eating) of emetic events. We conclude that this fixed low-dose granisetron plus dexamethasone regimen is a safe, convenient, and cost-effective antiemetic program for individuals receiving carboplatin-based chemotherapy.

Adult↗
PubMed1996

Paclitaxel delivered as a 3-hr infusion with cisplatin in patients with gynecologic cancers: unexpected incidence of neurotoxicity.

In an effort to develop a paclitaxel plus cisplatin combination chemotherapy regimen which can be easily employed in the outpatient setting, 38 patients (median age, 59; range, 39-72) with gynecological malignancies (20 ovarian; 6 primary peritoneal; 12 endometrial) seen at the Cleveland Clinic Foundation from June 1993 to May 1995 were administered 170 cycles of paclitaxel (135 or 175 mg/m2) over 3 hr followed by cisplatin (starting dose 75 mg/ m2). Of the 33 patients with elevated CA-125 levels prior to the initiation of chemotherapy, all experienced > 50% decreases in this antigen level, while 23/33 (70%) had > 90% reductions. In general, nonneurologic side effects were mild in severity and easily manageable. Unfortunately, 71% of the patients developed neurologic toxicity, with one-fifth of the treated population experiencing severe neurotoxic side effects (grade 3-4). We conclude that paclitaxel administered over 3 hr at a dose of 135 or 175 mg/m2, followed by cisplatin (75 mg/m2), is a highly active regimen in gynecologic malignancies. Unfortunately, in our experience, the incidence and severity of neurotoxicity with this regimen is considerably greater than that reported with paclitaxel administered over 24 hr in combination with cisplatin. As a result of the observed toxicity profile, this drug delivery schedule for cisplatin and paclitaxel cannot be recommended for general clinical use.

Adult↗
PubMed1996

Early outcome after open versus extraperitoneal endoscopic tension-free hernioplasty: a randomized clinical trial.

BACKGROUND: The use of minimal access surgery for repair of groin hernias is controversial. The aim of this study was to compare endoscopic tension-free hernia repair with open tension-free hernia repair within a randomized clinical trial. METHODS: One hundred twenty patients were randomized by four surgeons during a 1-year period. Early outcome measures were then analyzed by intention to treat. RESULTS: Median postoperative pain scores (63 [interquartile range (IQR), 23 to 81] versus 35 [IQR, 17 to 62]; p = 0.004) and analgesia requirements (2.5 [IQR, 2 to 4] doses verus 2.0 [IQR, 1 to 3] doses; p = 0.0008) were significantly less for patients undergoing endoscopic hernia repair. Hospital stay (1 [IQR, 0 to 1] day versus 2 [IQR, 1 to 2] days; p < 0.0001) was also significantly reduced for the endoscopic group. Wound complications occurred significantly more frequently in the open group. No difference in pulmonary function or metabolic response to trauma (interleukin-6, C-reactive protein, glucose, albumin) was observed between the groups. CONCLUSIONS: This study shows significant short-term advantages for endoscopic tension-free repair over open tension-free repair. However, larger studies with a longer follow-up period are required to establish the relative merits of both procedures in the management of patients with groin hernias.

Aged↗
PubMed1996

Positron emission tomography metabolic data corrected for cortical atrophy using magnetic resonance imaging.

The correct interpretation of clinical positron emission tomography (PET) data depends largely on the physical limits of the PET scanner. The partial volume effect (PVE) is related to the size of the studied object compared to the spatial resolution. It represents one of the most important limiting factors in quantitative data analysis. This effect is increased in the case of atrophy, as in patients with Alzheimer disease (AD), and it influences measurement of the metabolic reduction generally seen in cerebral degeneration. In this case, interpretation can be biased, because cortical activity will be underestimated due to the atrophy. In general, anatomical images of AD patients have shown diffuse atrophy, while PET studies have found widespread hypometabolism affecting the parietal and temporal lobes. Although hypometabolic areas usually correspond to atrophic regions, they also occur without such changes. Thus, the aim is to differentiate authentic hypometabolism (decrease of glucose consumption per unit volume of gray matter) from that due to PVE from atrophy (cell loss). Consequently, we are using a method for three-dimensional (3D) correction of human PET data with 3D magnetic resonance imaging (MRI). We measured atrophy and metabolism by using both T1-weighted MR images and high and medium resolution PET scans. We injected 12 patients and controls with [18F]fluorodeoxyglucose for glucose consumption measurements. Atrophy was estimated in the following way. We isolated the cerebral structures, using a segmentation technique on the MRI scans, into gray matter (GM), white matter, and cerebrospinal fluid. We superimposed the PET images onto the MR images to obtain anatomo-functional correlations. We degraded the segmented MR images to the resolution of the PET images by a convolution process to create a PET image correction map. We corrected the metabolic PET data for the PVE. We studied the cerebral metabolic rate of glucose in the GM where metabolic variation is the most relevant to AD. By dealing with problems relating to the sensitivity to the segmentation and to the PET-MRI coregistration, computation of MRI convolution processes provided the degree of PVE on a pixel-by-pixel basis, allowing correction of hypometabolisms contained in GM PET values. Global cortical metabolism increased after correction for PVE by, on average, 29 and 24% for tomographs acquired with medium (TTV03 LETI) and high (ECAT 953B CTI/Siemens) resolution, respectively, whereas the cortical metabolism increased by 75 and 65% for the respective tomographs in AD patients. The difference of metabolism between scans after correction for PVE was less than before correction, decreasing from 31 to 17%. This difference was most marked in the frontal and temporal lobes. Fusion imaging allowed correction for PVE in metabolic data using 3D MRI and determination of whether a change in the apparent radiotracer concentration in PET data reflected an alteration in GM volume, a change in radiotracer concentration per unit volume of GM, or both.

Adult↗