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Biomedical subjects

R R Davies

Publications and source records attributed to R R Davies.

At least 19 recordsLinked to original sources
PubMed2001

Stroke in surgery of the thoracic aorta: incidence, impact, etiology, and prevention.

OBJECTIVES: To determine the incidence, impact, etiology, and methods for prevention of stroke after surgery of the thoracic aorta. METHODS: A total of 317 thoracic aortic operations on 303 patients (194 male, 109 female) aged 13 to 87 years (mean 61 years) were reviewed. There were 218 procedures on the ascending aorta and arch and 99 on the descending aorta. Of the 218 procedures on the ascending aorta and arch, 86 involved cardiopulmonary bypass, 122 involved deep hypothermic circulatory arrest, 2 involved antegrade cerebral perfusion, and 8 involved "clamp and sew" or left heart bypass. Of the 99 procedures on the descending aorta, 20 involved "clamp and sew," 69 involved left heart or full bypass, and 10 involved deep hypothermic circulatory arrest. A total of 206 cases were elective and 97 were emergency operations. RESULTS: Twenty-three (7.3%) of 317 patients had a stroke. Fifteen strokes occurred in operations on the ascending aorta and 8 in operations on the descending aorta (6.9% vs 8.1%; P =.703). Stroke occurred in 16 (16.5%) of 97 emergency operations and 7 (3.4%) of 206 elective operations (P =.001). In the 300 patients surviving the operation, stroke was a significant predictor of postoperative death (9/23 [39.1%] vs 23/277 [8.3%]; P =.001). Analysis of operative reports, brain images, and neurologic consultations revealed 15 of the 23 strokes were embolic, 3 were ischemic, 3 hemorrhagic, and 2 indeterminate. Patients with stroke had longer intensive care unit stays (18.4 vs 6.8 days; P =.0001), longer times to extubation (12.7 vs 3.8 days; P <.0012), longer postoperative stays (31.4 vs 14.3 days; P =.001), and decreased age-adjusted survival (relative risk 2.775; P =.0013). After implementation of a rigorous antiembolic regimen, both strokes and mortality trended downward. CONCLUSIONS: (1) Stroke complicates surgery of both the ascending and descending thoracic aorta and warrants consideration in decision making. (2) Strokes are largely embolic. (3) Antiembolic measures for particles and air are essential, including gentle aortic manipulation, thorough debridement, transesophageal echocardiography to identify aortic atheromas, carbon dioxide flooding of the field, and (in descending cases) proximal clamp application before initiating femoral perfusion.

Aorta, Thoracic↗
PubMed1999

Artificial metalloenzymes based on protein cavities: exploring the effect of altering the metal ligand attachment position by site directed mutagenesis.

In an effort to construct catalysts with enzyme-like properties, we are employing a small, cavity-containing protein as a scaffold for the attachment of catalytic groups. In earlier work we demonstrated that a phenanthroline ligand could be introduced into the cavity of the protein ALBP and used to catalyze ester hydrolysis. To examine the effect of positioning the phenanthroline catalyst at different locations within the protein cavity, three new constructs--Phen60, Phen72 and Phen104--were prepared. Each new conjugate was characterized by UV/vis spectroscopy, fluorescence spectroscopy, guanidine hydrochloride denaturation, gel filtration chromatography, and CD spectroscopy to confirm the preparation of the desired construct. Analysis of reactions containing Ala-OiPr showed that Phen60 catalyzed ester hydrolysis with less selectivity than ALBP-Phen while Phen72 promoted this same reaction with higher selectivity. Reactions with Tyr-OMe were catalyzed with higher selectivity by Phen60 and more rapidly by Phen104. These results demonstrate that both the rates and selectivities of hydrolysis reactions catalyzed by these constructs are dependent on the precise site of attachment of the metal ligand within the protein cavity.

Carrier Proteins↗
PubMed1999

Familial patterns of thoracic aortic aneurysms.

HYPOTHESIS: To provide evidence that genetic factors contribute to the development of thoracic aortic aneurysms (TAA) by demonstrating familial patterns of the disease. DESIGN: Retrospective review. SETTING: University hospital. PATIENTS AND METHODS: We sought to identify familial patterns of TAA from a database of 598 patients evaluated or treated for TAA at the Yale Center for Thoracic Aortic Disease, New Haven, Conn, from January 1985 to August 1998. Of the 598 patients, 45 patients had a diagnosis of Marfan syndrome and 553 patients had no known history of any collagen vascular disorder. Of the 553 patients in the latter category, 398 patients had confirmed TAA, 66 had TAA with concomitant aortic dissections, and 89 had aortic dissections. From the group of 464 patients with TAA with or without concomitant aortic dissections, 2 interviewers attempted to contact 150 randomly selected patients for telephone screening to determine the presence of familial patterns of aortic disease. Fifteen of these patients were lost to follow-up. Complete medical and family histories of the remaining 135 patients (85 men, 50 women) were reviewed. Of the 135 individuals screened, 26 (18 men, 8 women) (19.3%) were found to belong to multiplex pedigrees. These 26 patients with familial nonsyndromic TAA were compared with the remaining 109 patients with sporadic TAA and the 45 patients with Marfan syndrome-associated TAA. MAIN OUTCOME MEASURES: Groups were examined for statistical differences in age and aortic size at the time of diagnosis, growth rates of TAA, and rates of concomitant diseases. Nonsyndromic family pedigrees were analyzed and potential modes of inheritance were determined. RESULTS: The mean age at presentation for patients with familial nonsyndromic TAA (56.8 years) was significantly younger than the mean age of presentation in sporadic cases (64.3 years, P< or =.03), and significantly older than that of patients with Marfan syndrome (24.8 years, P< or =.001). Patients with a family history of aortic aneurysms had faster growth rates (0.22 cm/y) compared with patients with sporadic TAA (0.03 cm/y) (P< or =.001) and patients with Marfan syndrome (0.10 cm/y) (P< or =.04). Familial nonsyndromic TAA in patients with a concomitant aortic dissection had a growth rate of 0.33 cm/y, which was greater than that of patients with sporadic TAA (0.10 cm/y) and patients with Marfan syndrome (0.08 cm/y) with associated aortic dissection. This growth of 0.33 cm/y was significantly faster than the overall growth rate estimate of aneurysms in patients with aortic dissection (0.14 cm/y) (P< or =.05). Ten pedigrees (38.5%) showed direct father to son transmission, consistent with an autosomal dominant mode of inheritance. Six family pedigrees (23.1%) suggested an autosomal dominant or X-linked mode of inheritance. Seven pedigrees (26.9%) suggested a recessive mode of inheritance; 2 an autosomal recessive mode, and 5 an X-linked recessive or autosomal recessive mode. The remaining 3 pedigrees displayed more complex modes of inheritance. CONCLUSIONS: This study supports the role of genetic factors influencing familial aggregation of TAA. Thoracic aortic aneurysms in association with multiplex pedigrees represent a new risk factor for aneurysm growth. Pedigree analysis suggests genetic heterogeneity. The primary mode of inheritance seems to be autosomal dominant, but X-linked dominant and recessive modes are also evident.

Adolescent↗
PubMed1998

Structural characterization of two synthetic catalysts based on adipocyte lipid-binding protein.

Adipocyte lipid-binding protein (ALBP) is a small (14.5 kDa) 10-stranded beta-barrel protein found in mammalian fat cells. The crystal structures of various holo-forms of ALBP have been solved and show the fatty acid ligand bound in a large (approximately 400 A3) cavity isolated from bulk solvent. Examination of the cavity suggests that it would be a good site for the creation of an artificial catalyst, as numerous well defined crystal structures of ALBP are available and past studies have shown the conformation to be reasonably tolerant to modification and mutagenesis. Previous work has shown ALBP to be a good protein scaffold for exploring enantio- and stereoselective reactions; two constructs, ALBP attached to either a pyridoxamine or a phenanthroline group at C117, have been chemically characterized. Both modified proteins have been crystallized and their structures solved and refined. The X-ray models have been used to examine the origin of the chiral selectivity seen in the products. It is apparent that these covalent adducts reduce the internal cavity volume, sterically limiting substrate interactions with the reactive groups, as well as solvent access to potential intermediates in the reaction pathway.

Adipocytes↗
PubMed1997

Prediction of vocational outcome based on clinical and demographic indicators among vocationally ready clients.

This study examined the clinical and demographic correlates of work skills and vocational outcome for persons with psychiatric disabilities. The same clinical, demographic, work skills, and vocational outcome instruments were administered to 275 persons working toward their vocational goals at three psychosocial rehabilitation centers. Data regarding vocational outcomes were collected quarterly over a period of 3 1/4 years. Using multivariate statistical techniques, clinical and demographic variables that predict work skills and future vocational outcomes were identified. The implications of the findings for program administrators, system planners, and researchers are discussed.

Adult↗
PubMed1995

Relationships between psychiatric symptomatology, work skills, and future vocational performance.

OBJECTIVE: Experts do not agree on what, if any, relationships exist between diagnosis, symptomatology, work skills, and the future vocational performance of persons with severe mental illness. The objective of this study was to longitudinally examine such relationships, using a sample of clients who were attending psychosocial rehabilitation programs. METHODS: Subjects were 275 clients of three psychosocial rehabilitation programs who had expressed a vocational goal. They were assessed at intake into the study and then quarterly until they left the rehabilitation program. The variables examined included symptoms, measured by the Brief Psychiatric Rating Scale; diagnosis; work skills, measured by the Griffiths Work Behavior Scale; and vocational status at end-point. RESULTS: Among subjects remaining in the study for one year, both symptomatology and work skills improved significantly. Moderately significant negative correlations were found between symptoms and work skills; subjects who became employed had lower symptom scores and higher work skills than persons who never became employed. CONCLUSIONS: Although a moderate relationship was found between symptomatology and work skills, symptoms should not be considered a proxy measure for vocational functioning among persons with severe mental illness. Participation in psychosocial rehabilitation programs appeared to have a salutary effect on symptoms and work skills.

Activities of Daily Living↗
PubMed1993

Suppressed TSH levels secondary to thyroxine replacement therapy are not associated with osteoporosis.

OBJECTIVE: Recent studies have suggested that patients receiving thyroxine are at increased risk of osteoporosis. We set out to measure bone mineral densities in two groups of post-menopausal women receiving thyroxine replacement therapy (those with serum TSH levels persistently suppressed or non-suppressed) and to compare the results in both groups with those of the local control population. DESIGN: Cross-sectional study. PATIENTS: Seventy-eight post-menopausal women who had been treated with thyroxine for primary autoimmune or idiopathic hypothyroidism for a minimum of 5 years, 44 with TSH persistently suppressed and 34 non-suppressed. One hundred and two control subjects. MEASUREMENTS: Forearm bone mineral density at proximal and distal sites as measured by single-photon absorptiometry. RESULTS: Results were expressed as Z-scores, i.e. number of standard deviations from the mean of a 5-year age-band from the local control population. Mean Z-scores at proximal and distal sites for the non-suppressed patients were -0.03 and -0.07 and for the suppressed patients were -0.20 and -0.25, representing a decrease in bone mineral density of at most 5% in the suppressed patients. The differences between the three groups were not statistically significant. CONCLUSION: In this patient population, the reduction in bone mineral density due to thyroxine is small. It is unlikely to be of clinical significance and should not on its own be an indication for reduction of thyroxine dose in patients who are clinically euthyroid.

Bone Density↗
PubMed1991

Metabolic control in diabetic subjects following myocardial infarction: difficulties in improving blood glucose levels by intravenous insulin infusion.

Optimal metabolic control during the first twelve hours after myocardial infarction may be associated with improved survival in diabetic subjects. A comparison of an intravenous insulin infusion regimen aimed at improving blood glucose levels (n = 35), with 'routine control' (n = 34) in the post infarction period has been carried out in diabetic subjects admitted to four Coronary Care Units over a two year period. However, glycaemic control was similar in both groups (intravenous infusion regimen, mean +/- SD capillary blood glucose 10.3 +/- 2.1 mmol/l, 'routine control' glucose 10.7 +/- 3.6 mmol/l). There were no differences in the rates of arrhythmias (31% v 32%), heart failure (46% v 47%) or mortality (17% v 18%). Mortality in diabetic subjects was lower than that quoted in previous studies but was higher than in non-diabetic subjects admitted to the Coronary Care Unit during the same period. Attempts to improve glycaemic control by means of intravenous insulin infusion were unsuccessful.

Aged↗
PubMed1989

The effect of thyroid status on the growth hormone response to growth hormone releasing hormone 1-44.

The growth hormone (GH) response to iv injection of GH releasing hormone 1-44 (GHRH 1-44) has been examined in 10 hyperthyroid and 6 hypothyroid patients. Both groups of patients were studied at presentation and when euthyroid (mean 5 months for hyperthyroid, 8 months for hypothyroid). Hyperthyroid subjects demonstrated a peak mean (+/- SE) level of 17.7 +/- 3.8 mU/l, with an integrated GH 29.3 +/- 6.4 mU/l.h. When euthyroid the peak mean level was 17.0 +/- 5.0 mU/l and the integrated GH 22.8 +/- 4.2 mU/l.h. Neither change was statistically significant. Hypothyroid subjects had a peak mean level of 5.0 +/- 2.7 mU/l and integrated GH of 5.9 +/- 1.7 mU/l.h and when euthyroid a peak mean level of 7.1 +/- 4.8 mU/l and integrated GH of 8.1 +/- 3.6 mU/l.h. Body weight did not change significantly in this group of hypothyroid subjects with prolonged treatment. The increase in GH response to GHRH previously reported following replacement therapy may reflect a treatment-induced decrease in body weight, or may be a short term effect.

Adolescent↗
PubMed1989

Somatostatin analogues in diabetes mellitus.

Growth hormone (GH) has long been considered to have importance in diabetes. With poor control in Type 1 diabetes GH levels are high and may aggravate poor metabolic control. Pharmacological suppression of GH release at this stage might reverse the metabolic changes, with the possible added benefit of lower plasma insulin concentrations. Diabetic patients with life-long GH deficiency rarely develop retinopathy, while pituitary ablation in patients with retinopathy often leads to improvement. Growth hormone release inhibiting factor, somatostatin, has a short plasma half-life, and multiple effects on the endocrine system and on the gastrointestinal tract, making it unsuitable for clinical use as a GH suppressant. Long-acting analogues have a long half-life, but remain non-specific in their effects. In Type 2 diabetes the analogue Octreotide suppresses insulin and glucagon release, leaving glucose levels either unchanged or somewhat elevated. Gastrointestinal side-effects have been common, but may diminish with long-term treatment. In Type 1 diabetes insulin requirement is decreased by Octreotide, but as in Type 2 diabetes GH suppression has been observed consistently only when the drug was given at bed-time. The decrease in insulin requirement may reflect suppression of glucagon release and/or gut effects. Amelioration of the 'dawn phenomenon' has not proved possible, and hypoglycaemia has proved a particular problem with Octreotide given subcutaneously at night. The lack of effective GH suppression (particularly in patients with proliferative retinopathy), lack of specificity, and the gut and hypoglycaemic side-effects, argue strongly against a clinical role for the current somatostatin analogues in diabetes mellitus.

Diabetes Mellitus, Type 1↗