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Biomedical subjects

R F Wilson

Publications and source records attributed to R F Wilson.

At least 19 recordsLinked to original sources

Coronary revascularisation in insulin-dependent diabetic patients with chronic renal failure.

Insulin-dependent diabetic patients found to have substantial coronary artery disease at the time of assessment for renal transplantation have 2-year survival of less than 50%. Because most of these patients have no angina symptoms their management is controversial. We tried to find out whether coronary artery revascularisation in such patients might decrease the combined incidence of unstable angina, myocardial infarction, and cardiac death. 151 consecutive insulin-dependent diabetic candidates for renal transplantation underwent coronary angiography. 31 had stenoses greater than 75% in one or more coronary arteries, atypical chest pain or no chest pain, and a left ventricular ejection fraction greater than 0.35. Of these, 26 agreed to be randomly assigned medical treatment (a calcium-channel-blocking drug plus aspirin) or revascularisation (angioplasty or coronary bypass surgery). 10 of 13 medically managed and 2 of 13 revascularised patients had a cardiovascular endpoint within a median of 8.4 months of coronary angiography (p < 0.01). 4 medically managed patients died of myocardial infarction during follow-up. Thus, revascularisation decreased the frequency of cardiac events in insulin-dependent diabetic patients with chronic renal failure and symptomless coronary artery stenoses. These findings suggest that diabetic renal transplant candidates should be screened for silent coronary artery disease, because revascularisation may decrease cardiac morbidity and mortality in this population.

Adult

End-diastolic volume. A better indicator of preload in the critically ill.

The relative value of pulmonary artery wedge pressure (PAWP) and right ventricular end-diastolic volume index (RVEDVI) as a reflection of the preload status of the critically ill was determined in 29 patients. Regression analysis of 131 hemodynamic studies demonstrated that cardiac index (CI) correlated better with RVEDVI (r = .61) than did PAWP (r = .42). Comparisons of PAWP and RVEDVI showed that possible misleading information concerning filling volume was provided by the PAWP at some time in 15 (52%) of these patients. In 15 patients given 22 fluid challenges, patients with a high PAWP (greater than or equal to 18 mm Hg) "responded" with a rise in CI more frequently than did patients with a low PAWP (less than 12 mm Hg). However, all eight patients with a RVEDVI less than 90 mL/m2 responded with a rise in CI, but all seven patients with a RVEDVI greater than or equal to 139 mL/m2 failed to respond. Thus, RVEDVI more accurately predicted preload recruitable increases in cardiac output.

Adult

The relationship between 48-h dental plaque accumulation in young human adults and the concentrations of hypothiocyanite, 'free' and 'total' lysozyme, lactoferrin and secretory immunoglobulin A in saliva.

Samples of resting and stimulated whole saliva and stimulated parotid saliva were collected from 40 young adults. One week later, after 48 h on a standardized diet without oral hygiene, all available plaque was collected for dry weighing. An inverse relationship was found between the 'free' lysozyme concentration in stimulated parotid saliva and plaque dry weight (r = -0.46, p less than 0.01). There were no other statistically significant correlation coefficients between concentrations of individual salivary constituents and plaque dry weight. However, cluster analysis of constituents in resting whole saliva revealed three groups of subjects with different salivary profiles, and in particular with different concentrations of both IgA and hypothiocyanite. Subsequent analysis revealed differences in plaque dry weight between the groups, demonstrating the potential biological significance of cluster membership based on salivary factors.

Adult

Effect of increased intra-abdominal pressure on mesenteric arterial and intestinal mucosal blood flow.

The effects of increased intra-abdominal pressure (IAP) on intestinal blood flow were studied in eight anesthetized pigs. Mesenteric artery blood flow (MABF), intestinal mucosal blood flow (IMBP), tonometric intramucosal pH (pHi), mean BP (MAP), cardiac output (CO), and pulmonary artery wedge pressure (PAWP) were measured as IAP was raised to 10, 20, 30, and 40 mm Hg by infusing lactated Ringer's solution (LR) into the peritoneal cavity. The MAP was kept constant with IV LR. Cardiac output fell slightly from 5.4 +/- 1.1 at baseline to 4.0 +/- 1.2 L/min at an IAP of 40 mm Hg (p less than 0.05). An IAP of 20 mm Hg caused significant decreases in MABF (73% +/- 22% of baseline) (p less than 0.05) and IMBF (61% + 12% of baseline) (p less than 0.05). These changes became progressively greater as the IAP was increased to 40 mm Hg. The pHi fell to 6.98 +/- 0.14 at 40 mm Hg IAP (p less than 0.01), indicating severe mucosal ischemia. Thus increased IAP can cause severe intestinal ischemia, which may be more important than the cardiac, pulmonary, and renal changes usually described.

Animals

Effect of increased intra-abdominal pressure on hepatic arterial, portal venous, and hepatic microcirculatory blood flow.

The effects of increased intra-abdominal pressure (IAP) on hepatic perfusion were studied in five anesthetized pigs. Doppler flow probes were used to measure hepatic artery blood flow (HABF) and portal venous blood flow (PVBF), and laser Doppler flowmetry was used to assess changes in hepatic microvascular blood flow (HMVBF). Hepatic blood flow responses to 10, 20, 30 and 40 mm Hg increases in IAP were assessed while the mean arterial BP (MAP) was maintained at baseline levels with IV crystalloid infusions. Although cardiac output and MAP were normal, HABF and HMVBF fell significantly with 10 mm IAP, and at 20 mm Hg IAP, HABF was 45% of the control value, PVBF was 65% of the control value, and HMVBF was 71% of the control value (p less than 0.05). At 30 and 40 mm Hg, hepatic blood flow was reduced even more. Thus, modest increases in IAP can cause significant impairment of hepatic perfusion despite a normal BP and cardiac output.

Abdomen

Prevalence of clinically undetected and untreated molar occlusal dentine caries in adolescents on the Isle of Wight.

The prevalence of clinically undetected occlusal dentine caries was determined in a group of adolescents living on the Isle of Wight by comparing data from clinical and radiographic examinations carried out in 1987. 6.3% of maxillary molars and 12.9% of mandibular molars which had been designated as clinically sound showed dentine caries on radiographs. Comparison of the radiographic data from 1975 and 1987 showed that there were more sound and fewer filled occlusal surfaces in 1987, but more primary occlusal caries. Approximately 50% of subjects examined in both 1975 and 1987 had at least one molar tooth with primary and/or secondary caries in dentine on radiograph.

Adolescent

Thrombolysis in unstable angina. Randomized double-blind trial of t-PA and placebo.

BACKGROUND: Because coronary thrombosis is important in the pathogenesis of unstable angina and correlates with in-hospital cardiac events, we hypothesized that thrombolytic therapy would decrease cardiac events. METHODS AND RESULTS: We randomized 70 patients with unstable angina to tissue-type plasminogen activator (t-PA) (0.49 MU/kg for 1 hour followed by 0.07 MU/kg per hour for 9 hours) or placebo. All patients received full doses of intravenous heparin for 96 hours and aspirin (325 mg beginning at 72 hours). The primary end points of the study were in-hospital death, myocardial infarction, and urgent revascularization. Three secondary end points were also evaluated. Myocardial perfusion was assessed with resting planar thallium scintigraphy 90 minutes after initiation of therapy. Silent ischemia was assessed with 48-hour Holter monitoring for ST shift beginning at time of initiation of drug therapy. Coronary angiography was performed at 18 +/- 6 hours and analyzed quantitatively to assess the stenosis responsible for unstable angina, the presence of intraluminal filling defects consistent with intracoronary thrombus, and stenosis morphology and severity. There was no difference in total in-hospital cardiac events between patients receiving t-PA (5% or 14%) and those receiving placebo (7% or 20%) (p = 0.83). Resting thallium defects were larger in the patients receiving t-PA than in those receiving placebo (130 +/- 118 versus 76 +/- 84 degrees, p less than 0.04), and this difference persisted when corrected for previous infarction. Although the numbers of patients with ST shift were similar, the duration of ST shift was significantly longer in the patients receiving t-PA than with placebo (20 +/- 46 versus 3 +/- 10 minutes, p less than 0.045). The frequency of intracoronary thrombi in patients with stenoses greater than 50% was significantly less in patients treated with t-PA (11 of 22, 52%) as compared with placebo (23 of 25, 92%) (p = 0.002), but there was no significant difference in minimal lesion cross-sectional area (0.49 +/- 0.42 versus 0.57 +/- 1.08 cm2, p = 0.75) or ulceration index (0.79 +/- 0.16 versus 0.77 +/- 0.15, p = 0.71) of the culprit artery. CONCLUSIONS: We conclude that a prolonged infusion of t-PA in unstable angina reduces intracoronary thrombi but does not significantly decrease in-hospital cardiac events. The sample size, however, does not provide sufficient power to rule out a treatment effect. Paradoxically, there appears to be an increase in ST shift and worsening of myocardial perfusion with t-PA compared with therapy with heparin alone.

Aged

Coronary angioplasty in cardiac transplant patients. Results of a multicenter study.

BACKGROUND: Accelerated allograft atherosclerosis is the main cause of death of cardiac transplant recipients after the first year after transplantation. Because no medical therapy is known to prevent or retard graft atherosclerosis and transplantation is associated with a shortened allograft survival, alternative, palliative therapy with percutaneous transluminal coronary angioplasty (PTCA) has been attempted. Because no single medical center has performed angioplasty in a large number of cardiac transplant recipients, representatives of 11 medical centers retrospectively analyzed their complete experience of coronary angioplasty in cardiac transplant patients to determine the safety, efficacy, limitations, and long-term outcome of angioplasty in allograft coronary vascular disease. METHODS AND RESULTS: Thirty-five patients underwent 51 angioplasty procedures for 95 lesions 46 +/- 5 months (mean +/- SEM) after transplantation. The primary indications for angioplasty included angiographic coronary disease in 22 cases (43%) and noninvasive evidence of ischemia in 18 procedures (35%). Angiographic success, defined as less than or equal to 50% post-PTCA stenosis, occurred in 88 of 95 lesions (93%). Mean pre-PTCA stenosis was 83 +/- 1.1%; mean post-PTCA stenosis was 29 +/- 2.1% (p less than 0.0001). Periprocedural complications included myocardial infarction and late in-hospital death in one patient and three groin hematomas. Twenty-three of the 35 patients (66%) had no major adverse outcome such as death, retransplantation, or myocardial infarction at 13 +/- 3 months after angioplasty. Four patients died less than 6 months after angioplasty, and four died more than 6 months after angioplasty (range, 6-23 months). Two patients had retransplantation 2 months after PTCA, and one patients had retransplantation 18 months after angioplasty. CONCLUSIONS: Coronary angioplasty may be applied in selected cardiac transplant recipients with comparable success and complication rates to routine angioplasty. Whether angioplasty prolongs allografts survival remains to be determined by a prospective, controlled trial.

Angioplasty, Balloon, Coronary

Prevalence of, and risk factors for, angiographically determined coronary artery disease in type I-diabetic patients with nephropathy.

BACKGROUND--Thirty-five percent of type I-diabetic patients are dead of coronary artery disease by age 55 years, and the risk of death is increased eightfold to 15-fold in patients with nephropathy. However, the prevalence of coronary artery disease with respect to age is unknown and few risk factors have been identified. METHODS--One hundred ten insulin-dependent diabetic patients underwent routine pretransplant coronary angiography and cardiac risk factor assessment. Angiograms were evaluated by two angiographers for presence or absence of coronary artery disease (CAD, defined as one or more coronary artery stenoses of 50% or greater in diameter, and no CAD, defined as no stenosis of 25% or greater in diameter, respectively). Prevalence of CAD by age was determined, and associated risk factors were defined. RESULTS--Fifty-two of 110 patients had CAD. Coronary artery disease prevalence increased significantly with age; 13 of 16 patients older than 45 years of age had CAD. For patients 35 years of age or younger, associated risk factors included a family history of premature myocardial infarction, higher hemoglobin A1c level, hypertension for more than 5 years, lower high-density lipoprotein level, and smoking for more than 5 pack-years. For patients between 35 and 45 years of age, associated risk factors included number of years of diabetes, higher hemoglobin A1c levels, and smoking more than 5 pack-years. CONCLUSIONS--In type I-diabetic patients with nephropathy, CAD prevalence increased significantly with age and was found in the majority of patients older than 45 years of age. Coronary artery disease risk factors operative in the general population were significantly associated with CAD in this high-risk group. In addition, a role for hyperglycemia in accelerated atherogenesis was supported by the association of both higher hemoglobin A1c levels and number of years of diabetes with CAD.

Adult

Electrolyte and acid-base changes with massive blood transfusions.

The case records of 471 patients with massive transfusions of ten or more units of bank blood within 24 hours were reviewed to analyze the electrolyte and acid-base changes. The patients who lived had a less severe acidosis (7.23 +/- 0.15 vs 7.11 +/- 0.17) and the HCO3 was higher (19.8 +/- 15.2 vs 13.4 +/- 6.8) (P less than 0.001). The mean anion gap, despite the low HCO3, was 11.8 +/- 7.8 mEq/L. A combined metabolic and respiratory acidosis, often following bicarbonate therapy, was fetal in 83 per cent (39/47). Serum potassium values (K) were high in 22 per cent and low in 18 per cent of patients. If potassium levels were "corrected" by subtracting 0.5 mEq/L for each 0.1 pH of metabolic acidosis, only 5 per cent of patients were hyperkalemic. Patients dying within 48 hours of the massive transfusions had higher potassium levels (4.9 +/- 1.1 vs 4.4 +/- 0.9; P less than 0.001). Ionized calcium levels (Ca++) were less than normal (1.13-1.32 mmol/L) in 94 per cent of patients and were very low (less than 0.70 mmol/L) in 46 per cent (108/234). The mortality rate with severe ionic hypocalcemia was 71 per cent (vs 40% in patients with more normal values); P less than 0.0001. pH, PCO2, K, and Ca++ must be followed closely with massive transfusions. Rapid correction of volume and pH, without overcorrection, is essential.

Blood Gas Analysis

Diagnosis of acute diffuse pulmonary infiltrates in immunosuppressed patients by open biopsy of the lung.

Herein is a review of the results of open biopsies of the lung performed upon immunosuppressed patients between the years 1982 and 1988. The goal was to assess the safety and value of the procedure on a group of patients who are many times in extremis because of multiorgan failure. Obtaining the correct diagnosis and establishing treatment poses a challenge. The study includes 74 patients. Fifty-four had malignant tumors; 20 had various diseases associated with immunosuppression. The biopsy was obtained from the left side in 65 instances. An adequate thoracotomy was done to permit exploration of the thoracic cavity and obtain a representative sample of tissue. The mortality rate related to the operation was 1.4 percent and the complication rate was 11.0 percent. Forty-six percent of the infiltrates were the result of infection. In 42 percent, a change in treatment was made. Thirty-two percent survived and were discharged from the hospital. Patients with adverse drug reaction, with nonspecific pneumonitis and with bacterial infection had a favorable prognosis and benefited most from open biopsy of the lung.

Acute Disease

Assessment of the human coronary circulation using a Doppler catheter.

Arteriographic estimates of stenosis severity can fail to reflect the impact of an individual stenosis on delivery of blood to the myocardium. Whether a coronary stenosis is truly flow-limiting can be determined by measuring hyperemic blood flow or coronary flow reserve; however, until recently, the tools needed to measure coronary flow reserve in humans--namely, a method of quantitating coronary blood flow in individual arteries and another method for producing maximal microvascular vasodilation--were not available. Over the last 8 years, our laboratory group has developed a catheter for measuring coronary blood flow velocity in humans, using the Doppler principle, and studied the effects of microvascular vasodilators. These studies have enabled us to measure coronary flow reserve in humans and to characterize some of the effects of focal and diffuse atherosclerosis on the coronary circulation. In addition, we have used flow reserve measurements in the diagnosis of microvascular dysfunction in patients with chest pain and normal coronary arteries and as a means of assessing noninvasive methods for detecting focal coronary artery disease.

Adenosine

Influence of thrombolytic agents on human platelet function.

In this study, we have evaluated the effects of four different thrombolytic agents, including Streptokinase from Hoechst and from Kabivitrum, Urokinase from Abbott and tissue plasminogen activator (t-PA) from Genetech, on platelet-rich plasma clots and platelet aggregation. At concentrations lower than 50 ugs/ml, t-PA had no inhibitory effect on clot retraction or platelet aggregation induced by weak or potent agonist. At a higher concentration (greater than 100 ugs/ml), t-PA specifically antagonized the action of thrombin on clot formation and platelet aggregation. Streptokinase (Kabivitrum) potentiated the action of weak agonists on platelet aggregation, but the same agent from Hoechst had no negative or positive influence. None of the drugs tested had an adverse effect on platelet function at suggested therapeutic levels. None of the thrombolytic agents were capable of dissociating preformed clots made from platelet-rich plasma. However, all of them caused lysis of whole blood clots. Also, prior incubation of plasma alone or platelet-rich plasma with any of the agents prevented subsequent clot formation. The studies demonstrate that thrombolytic drugs at therapeutic concentrations do not affect platelet function adversely. They have a potent effect on whole blood clots, but not on clots from platelet-rich plasma. Therefore, platelets may play a critical role in determining the degree of reperfusion and the frequency of reocclusion following treatment with thrombolytic agents in vivo.

Blood Coagulation

Relationship between calcium and inorganic phosphorus concentrations of both resting and stimulated saliva and dental plaque in children and young adults.

Calcium and inorganic phosphorus concentrations of both resting and paraffin-wax stimulated whole saliva and dental plaque were estimated in 39 young adults and 98 children aged 12-14 yr. Plaque was collected from the adults after 48 h without tooth-brushing and consumption of a standardized diet. Plaque was collected from the children without any dietary or oral hygiene restrictions. The results from the study with children provided consistent evidence for a statistically significant relationship between salivary and plaque concentrations of both calcium and inorganic phosphorus. However, multiple regression indicated that only the concentrations in the stimulated secretion were directly associated with concentrations in plaque. The apparent relationship between concentrations in resting saliva and plaque was due to correlation between resting and stimulated saliva. These relationships were less apparent in the young adults, in whom the controlled conditions resulted in a narrower range of mineral concentrations in dental plaque.

Adolescent

A comparison of passive and active shunting for bypass of the retrohepatic IVC.

In order to provide improved shunting of caval blood around the liver for major juxtahepatic venous injuries, a modification of the venovenous bypass (active shunt) used in liver transplantation was developed. Using a porcine model, hemodynamic comparisons of active shunting with an interposed Bio-Medicus pump (group I: n = 6) and passive shunting (group II: n = 4) around the liver for 60 minutes were made. One end of the shunt was placed in the infrahepatic cava and the other end was inserted into the right atrium. Systolic blood pressure (sBP) and cardiac output (CO) were well maintained in group I. However, with passive shunting (group II), sBP fell from 134 +/- 28 to 83 +/- 28 mm Hg (p less than 0.05) and CO fell from 4.1 +/- 0.07 to 1.3 +/- 0.5 L/min (p less than 0.001) after 1 hour. The well-maintained sBP and CO in group I were associated with much better shunt flow rates than in group II (31 +/- 7 vs. 11 +/- 3 mL/kg/min) (p less than 0.001). The cause of the fall in sBP and CO with the passive shunt (group II) in spite of a well-maintained PAWP is unclear at this time. Thus, it appears that active shunting of blood around the liver using a venovenous bypass with a pump is much superior hemodynamically to passive shunting, which relies only on hydrostatic pressure.

Animals