PubMed HealthSearch

Biomedical subjects

C Ryan

Publications and source records attributed to C Ryan.

At least 37 records · Page 2Linked to original sources

Hypoglycemia unawareness in IDDM.

OBJECTIVE: To assess the characteristics of patients with hypoglycemia unawareness (development of neuroglycopenia without appropriate prior autonomic warning symptoms) and its predisposing factors. RESEARCH DESIGN AND METHODS: We studied 43 insulin-dependent diabetes mellitus patients who were objectively categorized as having or not having hypoglycemia using the stepped hypoglycemic clamp technique in which plasma glucose was clamped at plateaus of 4.3, 3.6, 3.0, and 2.3 mmol/l and a statistical criterion (onset of autonomic warning symptoms at a plasma glucose concentration 2 SD below normal) and examined their clinical characteristics and hormonal, symptomatic, and cognitive responses. RESULTS: Eleven (26%) of the patients were classified as having hypoglycemia unawareness. Compared with the other patients, unaware patients had a lower HbA1c level (P < 0.01), a longer duration of diabetes (P < 0.01), and a history of more severe hypoglycemia (P < 0.003). During experimental hypoglycemia, counterregulatory hormone responses, neuroglycopenic symptoms, and cognitive dysfunction all began at lower plasma glucose concentrations in unaware patients (P < 0.01, 0.03, and 0.01, respectively). Moreover, although the magnitudes of their plasma catecholamine responses and autonomic symptoms were reduced (both, P < 0.01), the plasma catecholamine levels at which autonomic symptoms began was not altered. Finally, as seen from glucose infusion rates necessary to maintain identical plasma glucose levels, patients with hypoglycemia unawareness had increased sensitivity to insulin (P < 0.001). CONCLUSIONS: Our results confirm an association between hypoglycemia unawareness and duration of diabetes, glycemic control, and occurrence of severe hypoglycemia, and in addition provide evidence that both autonomic and neuroglycopenic symptoms are affected and that insulin sensitivity is increased, but beta-adrenergic sensitivity is not diminished.

Adult

Parasuicide.

Explore the source record for details and available documents.

Attitude of Health Personnel

Usefulness of supine bicycle stress echocardiography for detection of restenosis after percutaneous transluminal coronary angioplasty.

The role of supine bicycle stress echocardiography (SBSE) for detecting restenosis after percutaneous transluminal coronary angioplasty (PTCA) was evaluated in 80 patients: 41 (51%) with single and 39 (49%) with multivessel PTCA (total 129 dilated vessels). Total revascularization was performed in 54 (68%) and partial revascularization in 26 (32%) patients. Restenosis was angiographically demonstrated in 60 patients (75%) and in 72 vessels (56%) 6.1 +/- 2.9 months after PTCA. The results for detecting restenosis were: (1) SBSE versus exercise electrocardiographic sensitivity, 87 versus 55% (p < 0.001); (2) specificity, 95 versus 79%; and (3) accuracy, 89 versus 61% (p < 0.001). SBSE was 83% sensitive, 95% specific and 88% accurate for restenosis detection in specific vessels with comparable results for single versus multivessel PTCA and total versus partial revascularization. Sensitivity, specificity and accuracy were: 91, 93 and 91% for the left anterior descending coronary artery; 77, 94 and 85% for the right coronary artery; and 76, 96 and 88% for the left circumflex coronary artery. Ninety-four percent of the nondilated diseased vessels were correctly identified. It is concluded that SBSE is an excellent tool for identifying restenosis after PTCA.

Aged

Memory performance during the Amytal test in patients with non-temporal lobe epilepsy.

PROBLEM: The amobarbital (Amytal) sodium test has been considered an indispensable tool in the presurgical examination of patients for epilepsy surgery. However, the accuracy of the Amytal test for predicting memory deficits, especially the amnestic syndrome, has been questioned. METHOD: The Amytal test was administered bilaterally to three groups of patients with epilepsy: temporal lobe (n = 76), frontal lobe (n = 25), and primary generalized (n = 8). Each injected hemisphere for each patient was graded pass or fail for its ability to support memory. RESULTS: The percentages of hemispheres that failed the Amytal test were 31% for the temporal lobe group, 32% for the frontal lobe group, and 56% for the primary generalized group. CONCLUSIONS: The Amytal test may be a sensitive measure of memory dysfunction. However, the high percentage of failures remains at variance with the rare incidence of the amnestic syndrome, suggesting a low specificity for this test.

Adolescent

Heat shock protein is a unique marker of growth arrest during macrophage differentiation of HL-60 cells.

Prior to morphologic and functional maturation, terminally differentiating hematopoietic cells first exit the cell cycle and undergo growth arrest. Relatively little is known about which molecules regulate differentiation-induced growth arrest. In the present report, we sought to determine whether the mammalian low molecular weight heat shock protein (hsp28) was a candidate growth-regulatory molecule during human hematopoiesis. To this end, hsp28 protein expression was examined during phorbol ester (PMA)-induced macrophage differentiation of the human HL-60 promyelocytic leukemic cell line. Whereas hsp28 was constitutively expressed at relatively low levels in an unphosphorylated state, hsp28 was rapidly phosphorylated within 4 hr following PMA-induced differentiation, preceding increased hsp28 protein levels at 24-48 h. In contrast to other differentiative agents, hsp28 steady state mRNA and protein were regulated concordantly in response to macrophage differentiation. More importantly, these changes were transient, and occurred concomitant with the down-regulation of cellular proliferation and the onset of G1 phase cell cycle arrest. In total, these observations implicate hsp28 as an intermediary in the myelomonocytic differentiative pathway of promyelocytic leukemic cells, and will shed light on the events regulating this process.

Biomarkers

An in-frame insertion into the Sindbis virus 6K gene leads to defective proteolytic processing of the virus glycoproteins, a trans-dominant negative inhibition of normal virus formation, and interference in virus shut off of host-cell protein synthesis.

Encoded in the genomes of all alphaviruses is a hydrophobic polypeptide of 55 amino acids, which is post-translationally modified with 4 covalently bound palmitic acids. This protein, noted as 6K, associates with membranes and is transported along with the two virus transmembranal glycoproteins to the site of virus assembly at the infected cell's plasma membrane. Previous studies showed that mutations in the 6K protein led to the slow release of aberrant, multi-cored infectious virions. In this paper, we report that an in-frame insertion of 45 nucleotides into an internal site of the 6K gene of Sindbis virus produced single-cored infectious particles at about 5% the yield of wild-type virus when the mutant was grown on avian, mammalian, and insect cells. Although the 15 amino acids were inserted at position 29 of the 55-amino-acid 6K protein, the mutation interfered with the cotranslational proteolytic processing that cleaves the 6K at its amino terminus from the Sindbis virus p62 glycoprotein and at its carboxyl terminus from the E1 glycoprotein. As a result, the amounts of normal p62 and E1 proteins were only half that made in cells infected with wild-type virus. In addition, the post-translational proteolytic conversion of p62 to E2 occurred at 10% the rate of wild-type proteins and the extensive fatty acylation normally detected on wild-type 6K protein was not found on the altered 6K protein. None of the mutated 6K protein was detected in virions, which were morphologically indistinguishable from wild-type virus. The mutant 6K virions also were similar to wild type in their rate of attachment, uncoating, and formation of an early nonstructural virus protein in avian cells. When compared with the wild-type virus, 6K29-infected cells exhibited a decreased rate of host-cell protein synthesis shut off. However, the rates of virus capsid synthesis were the same, indicating that capsid protein, per se, is not involved in shut off of host-cell protein synthesis. In complementation studies, this mutant exhibited a trans-dominant phenotype. These data provide clues about the topology of 6K protein in the membrane and its function in virus maturation.

Amino Acid Sequence

Coronary rotational ablation: initial experience in 302 procedures.

OBJECTIVES: The aim of this study was to assess the utility of percutaneous transluminal coronary rotational ablation in the treatment of coronary artery disease. BACKGROUND: Although numerous advances have been made in the treatment of coronary artery disease, there are lesions with complex morphology that are not amenable to current intravascular therapy. METHODS: A consecutive series of 242 patients having 302 coronary rotational ablation procedures was analyzed. One hundred nineteen (49%) of the patients had previously undergone attempted coronary angioplasty, which was unsuccessful in 31 patients (13%). The left ventricular ejection fraction was normal in 196 patients (81%). The ablation procedure was attempted in 308 vessels and 346 lesions. Of the 346 lesions treated, 26 (7.5%) were classified as American College of Cardiology/American Heart Association type A, and 320 (92.5%) as either type B or type C. RESULTS: Procedural success was achieved in 284 (94%) of the 302 procedures and 330 (95.4%) of the 346 lesions in which ablation was attempted. Five procedures (1.7%) were unsuccessful, but no cardiac event occurred during the hospital stay. A major cardiac event occurred in 13 cases (4.3%); 9 (3%) of these complications were due to the ablation procedure. Six patients sustained a Q wave myocardial infarction alone, two had a Q wave infarction and required emergency surgery and one needed emergency surgery but did not have a Q wave infarction. No procedural deaths were attributed to the ablation procedure. Follow-up has been obtained in 182 of the 242 patients at a mean interval of 9 +/- 5 months. Of the 182 patients, 174 (95.6%) were alive and free of myocardial infarction. Angiographic follow-up is available thus far in 87 patients. By combining angiographic and clinical outcome, an overall estimated restenosis rate of 37.4% (68 of 182) was calculated. CONCLUSIONS: These data suggest that coronary rotational ablation can be performed on lesions with a variety of morphologic features with high initial success rates. The overall rate of restenosis is similar to that of balloon angioplasty.

Angioplasty, Balloon, Coronary

A proximity-contingent stereoscopic depth aftereffect: evidence for adaptation to disparity gradients.

Prolonged inspection of a surface slanted in the third dimension of visual space typically results in a negative aftereffect such that, after adaptation, a surface in the fronto-parallel plane will appear slanted in the opposite direction. Binocular disparity is not necessary to generate such effects, since they can be obtained monocularly, presumably via adaptation to texture gradient. Six experiments demonstrated durable stereoscopic depth aftereffects in the absence of a texture gradient--by using discrete disparate objects rather than slanted surfaces--and demonstrated that adaptation was to the interobject disparity gradient rather than to the relative disparity of the objects per se. The disparity required to null the obtained aftereffects was inversely proportional to the horizontal separation of elements, for a constant disparity, and directly proportional to the separation of subsequently presented probes. When elements differed in depth (disparity), but were not laterally separated, nulling disparity was significant but invariant with changes in the horizontal separation of probe elements. In that case, adaptation was (i) either to the disparity gradient generated by the vertical separation of probe elements (of which the relative disparity component was tapped); or (ii) to relative disparity per se.

Adult

Glucose dynamics and gluconeogenesis during and after prolonged swimming in rats.

Glucose fluxes and, in particular, gluconeogenic rate were examined during and after prolonged submaximal exercise represented by a 4-h swim and 3-h recovery in 12-h-fasted previously catheterized rats. The metabolic clearance rate and production rate of glucose were measured using an infusion of [6-3H]glucose, and gluconeogenesis was assessed from the incorporation of 14C from [14C]bicarbonate into glucose. Immediately after exercise and after the 3-h recovery, liver glycogen was also determined. During exercise, euglycemia was maintained while glucose production and utilization doubled from 1.58 +/- 0.17 to 3.58 +/- 0.21 mg/min. During recovery, glucose concentrations increased to 131.0 +/- 5.8 vs. 110.8 +/- 5.1 mg/dl for controls (P < 0.05), because the decline in glucose production rate lagged behind the decline in metabolic clearance rate. The index of gluconeogenesis coupled with a metabolic correction factor indicates that gluconeogenesis was the primary source of glucose during swimming and recovery and that the principal substrates were at the level of pyruvate. CO2 production rates calculated using plasma CO2 and label concentrations doubled during exercise. Little repletion of liver glycogen was seen after exercise, indicating that the increased production of glucose after exercise is directed primarily toward the repletion of muscle glycogen. Swimming is therefore a useful model of low-intensity exercise easily implemented in untrained animals. [14C]bicarbonate can be used in the estimation of gluconeogenic rates during exercise.

Animals

Influence of plasma glucose rate of decrease on hierarchy of responses to hypoglycemia.

To test the hypothesis that the rate of decrease in plasma glucose concentration may affect the hierarchy of responses to hypoglycemia, we compared plasma couterregulatory hormone concentrations, autonomic and neuroglycopenic symptom scores, and cognitive function test performance in 10 normal volunteers whose plasma glucose concentration was either rapidly (over 30 min) decreased to 3.7 mmol (66 mg/dL) or was slowly decreased in a stepwise manner to plateaus of 4.3 mmol (78 mg/dL), 3.7 mmol (66 mg/dL), 3.0 mmol (54 mg/dL), and 2.3 mmol (42 mg/dL). Comparable plasma counterregulatory hormone concentrations and autonomic symptom scores were observed in both sets of experiments during the 3.7 mmol (66 mg/dL) plateaus. In the stepwise decrement experiments, significant increases in neuroglycopenic symptom scores and deterioration in cognitive performance occurred only during the last glycemic plateau (2.3 mmol, 42 mg/dL). In the rapid decrement experiments, no increase in neuroglycopenic symptom score or deterioration in cognitive performance was observed during the 3.7 mmol (66 mg/dL) plateau. We, therefore, conclude that in normal volunteers the rate of decrease in plasma glucose concentration does not affect the hierarchy of responses to hypoglycemia.

Adult

Vitamin D deficiency found in the diet of the elderly in South Carolina.

Dietary intake of vitamin D was assessed from a 24-hour food recall collected from 293 independent living adults 55 years of age or older who participated in the South Carolina Nutrition Survey. Mean vitamin D intake was only 46 percent of the RDA. The data in this study indicated that insufficient dietary intake of vitamin D is prevalent among older South Carolinians. Possible methods to correct this include: increased exposure to the sun, increased intake of food sources containing this nutrient or prescribing a vitamin D supplement.

Aged

Growth arrest of human B lymphocytes is accompanied by induction of the low molecular weight mammalian heat shock protein (Hsp28).

A large number of protein and molecular markers have been identified that delineate the early stages of human B cell activation and proliferation. In contrast, few if any molecules are transiently expressed precisely as activated B cells stop proliferating and undergo growth arrest. We demonstrate that the low molecular weight heat shock protein (hsp28) exhibits unique induction kinetics that specifically demarcates this interval. After mitogenic activation of unstimulated splenic B cells, hsp28 protein and phosphorylation transiently increase coinciding precisely with the peak of cellular proliferation and the onset of growth arrest. Although most neoplastic B cells constitutively express hsp28, three cell lines were identified that were hsp28-. No differences in phenotype or growth kinetics were detected between hsp28+ and hsp28- neoplastic B cells demonstrating that hsp28 expression is not essential for cell growth. However, when treated with phorbol ester or heat shock, these hsp28- cell lines synthesize hsp28 followed by the onset growth arrest. The consistency with which hsp28 induction transiently delineates the interval from peak proliferation to the onset of growth arrest suggests hsp28 itself is likely to be involved in regulating this process.

B-Lymphocytes

Inhibitory effects of HSP70 chaperones on nascent polypeptides.

Several of the major heat shock proteins (HSPs) function normally as molecular chaperones to prevent aggregation of immature polypeptides and thereby facilitate folding and oligomerization. To determine their effect on nascent polypeptides, we added purified preparations of different isoforms of HSP70 to in vitro translation reactions primed by the 26S mRNA of Sindbis virus, which encodes an autoprotease that functions cotranslationally, or by the mRNA encoding the yeast vacuolar H+ATPase, which is formed by a novel transpeptidase activity that removes the central region of the initial polypeptide. In the presence of HSP70s both the autoprotease and transpeptidase activities were inhibited, indicating that these chaperones can interact with nascent polypeptides and, in the cases studied here, perturb their normal structures.

Animals

Lesion morphology and coronary angioplasty: current experience and analysis.

From July 1, 1990 to February 28, 1991, 533 consecutive patients with 764 target vessels and 1,000 lesions underwent coronary angioplasty. Procedural success was achieved in 92.3%, untoward (major cardiac) events occurred in 3% (0.8% myocardial infarction, 1.3% emergency coronary bypass grafting and 0.9% both; there were no deaths). An unsuccessful uncomplicated outcome occurred in 4.7%. Lesion analysis using a modified American College of Cardiology/American Heart Association classification system showed that 8% were type A, 47.5% were type B and 44.5% were type C (36% of type B and 11% of type C were occlusions). Angioplasty success was achieved in 99% of type A, 92% of type B and 90% of type C lesions (A vs. B, p less than 0.05; B vs. C, p = NS; A vs. C, p less than 0.01). Untoward events occurred in 1.2% of type A, 1.9% of type B and 2% of type C lesions (p = NS). An unsuccessful uncomplicated outcome occurred in 0% of type A, 6% of type B and 7% of type C lesions (A vs. B, p less than 0.05; B vs. C, p = NS; A vs. C, p less than 0.05). Among the unsuccessful uncomplicated outcome group, occlusion occurred in 49%: 38% of type B and 59% of type C lesions. With B1 and B2 subtypes, success was obtained in 95% and 89.5% and untoward events occurred in 1.5% and 2.3% and an unsuccessful uncomplicated outcome in 3.7% and 8%, respectively. C1 and C2 subtyping showed success in 91% and 86%, untoward events in 1.3% and 6% and an unsuccessful uncomplicated outcome in 7.5% and 8.5%, respectively. Among the 764 vessels, success was obtained in 89.5% and untoward events occurred in 2.5% and an unsuccessful uncomplicated outcome in 8%. Assessment of lesion-vessel combinations showed a less favorable outcome with type C lesions and combinations of A-B, B-C and multiple (more than three lesions) type B and C vessels. Statistical analysis of morphologic factors associated with angioplasty success included absence of (old) occlusion (p less than 0.0001) and unprotected bifurcation lesion (p less than 0.001), decreasing lesion length (p less than 0.003) and no thrombus (p less than 0.03). The only significant factor associated with untoward events was the presence of thrombus (p less than 0.003). Predictors of an unsuccessful uncomplicated outcome included old occlusion (p less than 0.0001) and increasing lesion length (greater than 20 mm) (p less than 0.001), unprotected bifurcation lesion (p less than 0.05) and thrombus (p less than 0.03).

Angioplasty, Balloon, Coronary

Perspective, orientation disparity, and anisotropy in stereoscopic slant perception.

Stereoscopic depth estimates are not predictable from the geometry of point disparities. The configural properties of surfaces (surface contours) may play an important role in determining, for example, slant responses to a disparity gradient, and the marked anisotropy in favour of slant around a horizontal axis. It has been argued that variation in slant magnitude are attributable to the degree of perspective conflict present and that anisotropy is attributable to orientation disparity, which varies with the axis of slant. Three experiments were conducted in which configural properties were varied to try and tease apart the respective roles of orientation disparity and conflicting perspective in determining stereoscopic slant perception and slant axis anisotropy. The results could not be accounted for by the magnitude of the orientation disparities present. Conflicting perspective cues appeared to play a role but only for slant around a vertical axis. It was concluded that there are important configural effects in stereopsis attributable neither to orientation disparity nor to perspective.

Anisotropy

Multicenter evaluation of five commercial rubella virus immunoglobulin G kits which report in international units per milliliter.

In a multicenter study, the consistency of international units expressed by five commercially available rubella virus immunoglobulin G kits was evaluated. The linearity and within-run and between-run precision were determined for each kit. All kits demonstrated good linearity and had within-run and between-run precision coefficients of variation ranging from 5.1 to 21.7% and from 9.5 to 51.0%, respectively. To compare the international units expressed, the results from 40 samples tested in duplicate were compared with the results of a reference enzyme immunoassay calibrated with World Health Organization international standard serum and a hemagglutination inhibition test. The results of the kits were plotted against those of the reference tests, and linear regression analysis was applied. The Pearson correlation coefficient ranged from 0.64 to 0.75 when the commercial kit results were compared with those of the reference enzyme immunoassay, indicating only a moderate degree of correlation. Therefore, the international units expressed by the commercial kits are insufficiently consistent to be of practical use in diagnostic clinical microbiology.

Antibodies, Viral