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Biomedical subjects

G Marshall

Publications and source records attributed to G Marshall.

At least 19 recordsLinked to original sources

Salvage angioplasty: an alternative to high risk surgery for unstable angina?

This prospective, Human Subjects Committee and Ethics Committee approved investigation was performed to determine if coronary angioplasty (PTCA) might be a reasonable alternative revascularization method for unstable angina patients thought to be at high risk for operative (CABG) mortality. Between March 1990 and October 1991, thirty-four consecutive patients with medically refractory rest angina were deamed to have high risk of surgical mortality and underwent PTCA without surgical backup. Predicted operative mortality was calculated for each patient based upon the VA Surgical Risk Assessment model. Angioplasty of 52 vessels was attempted. Reduction in lumenal narrowing to < 50% and improved angiographic flow was obtained in 47 vessels. There were four complicating infarctions. One death occurred in the lab, and three patients with unsuccessful angioplasty died within 30 days of pump failure. Relief of angina occurred in 30/34. Thirty patients were discharged home. In follow-up from 1 to 12 months, there have been 2 late sudden deaths at 4 months and 9 months, 1 death from lung cancer; 4 patients have stable exertional angina; 2 are awaiting heart transplant but are pain free, and one patient who had PTCA during cardiogenic shock from acute myocardial infarction had elective coronary artery bypass surgery. There have been no late myocardial infarctions. The observed angioplasty 30-day mortality of 11.8% (95% confidence limit 1% to 22.6%) compares favorably with the predicted operative mortality of 23.8% for this group. This prospective but non-randomized series supports the concept that balloon angioplasty may be a reasonable alternative to surgical intervention in some patients with unstable angina and high risk for surgery. A prospective randomized trial is warranted.

Adult

Comparison of tensile strength of solder joints by infrared and conventional torch technique.

Fabrication of a fixed partial denture may require a soldering step. This study compared soldering by a conventional torch procedure with an infrared soldering technique. Comparisons were made for tensile strength, porosity, and time efficiency between the two methods. No significant difference was found in ultimate tensile strength between the two types of solder joints and the nonsoldered control samples. Random samples photographed with a scanning electron microscope revealed no difference in joint porosity between the two techniques. Torch soldering took consistently less time that infrared soldering.

Dental Alloys

Prevention of post-ischemic brain lipid conjugated diene production and neurological injury by hydroxyethyl starch-conjugated deferoxamine.

Hydroxyethyl starch conjugated deferoxamine (DFO) was administered to rats following resuscitation from 6.5 min cardiac arrest (CA) in an attempt to prevent the iron-catalyzed production of oxygen free radicals which may lead to neurologic injury and ultimately death following restoration of spontaneous circulation (ROSC). Brain conjugated dienes were analyzed spectrophotometrically 4 and 24 hr following ROSC, and were found to be significantly elevated when compared to non-ischemic controls. Hydroxyethyl starch-DFO treated rats demonstrated no increased conjugated diene production at either period. Neurologic injury was significantly less in drug treated rats surviving 24 or 72 hours when compared to controls. While mortality was similar in drug treated or control rats for the first 24 hours following ROSC, delayed mortality (days 1-10) was significantly less in drug treated animals, presumably as a result of neurologic protection afforded by post-ischemic drug administration. Administration of DFO conjugated to hydroxyethyl starch appears to modulate the neurologic injury which occurs during brain ischemia and reperfusion.

Alkenes

Limited joint mobility in subjects with insulin dependent diabetes mellitus: relationship with eye and kidney complications.

Three hundred and fifty seven subjects (178 males and 179 females) with insulin dependent diabetes mellitus were evaluated for the presence of limited joint mobility of the interphalangeal joints. Sixty six subjects (19%) had stage 1 and 26 subjects (7%) had stage 2 involvement of their interphalangeal joints. The presence of contractures was significantly related to mean longitudinal glycated haemoglobin (HbA1) concentrations, duration of diabetes, age of onset, mean longitudinal cholesterol concentrations and blood pressure. Limited joint mobility was also significantly associated with early diabetic retinopathy and raised albumin excretion rates. Limited joint mobility remained a significant factor in the logistic regression model for albuminuria and grade of retinopathy when controlled for smoking, cholesterol concentrations, duration of diabetes, age, gender, and blood pressure. However, limited joint mobility was only significantly associated with diabetic retinopathy when the effect of HbA1 concentrations was included in the multivariate model.

Adolescent

Cigarette smoking increases the risk of albuminuria among subjects with type I diabetes.

The effect of cigarette smoking on diabetic renal and retinal complications was evaluated in 359 young subjects with insulin-dependent diabetes mellitus. The prevalence of increased albumin excretion rates was 2.8 times higher in smokers than nonsmokers. Mean glycohemoglobin levels and duration of diabetes were also significant factors in the development of diabetic nephropathy and retinopathy in a logistic regression model. Smoking remained a significant factor in the logistic regression model for albuminuria (but not retinopathy) when controlled for glycohemoglobin level, duration of diabetes, age, gender, and blood pressure. The progression of albuminuria and of retinopathy was also greater in smokers. Albuminuria improved significantly when subjects ceased smoking. It is concluded that cigarette smoking is an independent risk factor and is associated with the development and progression of early diabetic renal damage (albuminuria) and with the worsening of retinal disease in young subjects with diabetes.

Adolescent

Retinal changes and alterations in blood pressure and albumin excretion rate (AER) during exercise in type 1 diabetes.

The association of retinal changes with exercise microalbuminuria and with changes in systolic and diastolic blood pressure (BP) were evaluated in 162 young subjects with insulin-dependent (type 1) diabetes mellitus. Higher systolic and diastolic BPs at rest or after 10 or 20 min of exercise were significantly associated with more severe retinal changes in the subjects with diabetes compared to controls (P less than 0.02; global ANOVA). The mean (+/- SEM) exercise albumin excretion rate (AER) was 17.6 +/- 3.1 if there was no evidence of retinopathy compared to 81.5 +/- 23.5 when only microaneurysms were detected and 467.1 +/- 133.3 when more severe retinopathy was present. The percentage of subjects with abnormal AERs for these three retinal groups was 13, 30 and 60, respectively. (P less than 0.0001, chi-square test). It is clear that retinal changes relate to early renal changes, as monitored by exercise AERs and changes in resting and exercise BPs. It is concluded that the renal and retinal microvascular changes occur concurrently in young subjects with type 1 diabetes.

Adult

Prophylactic use of ganciclovir in allogeneic bone marrow transplantation: absence of clinical cytomegalovirus infection.

Ganciclovir was given prophylactically to 25 patients receiving allogeneic bone marrow transplants for haematological malignancy. Patients who were seropositive for cytomegalovirus (CMV) pre-transplant were given ganciclovir both pre- and post-transplant. Those who were CMV seronegative, but who received marrow from a CMV seropositive donor, received ganciclovir post-transplant. No nonhaemopoietic toxicity was observed. Toxicity was restricted to late reversible haematological toxicity in four of the 19 evaluable patients (one thrombocytopenia, one pancytopenia, two leucopenia). No CMV interstitial pneumonitis (IP) was observed, nor were any other clinically manifest CMV infections detected. Sixteen patients remain alive at greater than 84 to greater than 518 d post-transplant. In a retrospective comparison of 152 recipients of allogeneic transplants for haematological malignancy not given prophylactic ganciclovir, and in whom either the recipient or the donor or both were CMV seropositive, the incidence of all clinically manifest CMV infections was 23% (P = 0.02) and that of CMV IP 17% (P = 0.05). If only patients in the study group and the control group receiving the same cyclosporin/short methotrexate prophylactic immune suppressive regimen, the same prophylactic acyclovir regimen and the same CMV and leucocyte-filtered blood product transfusion strategy were considered, the incidence of all clinically manifest CMV infections in the control group was 24% (P = 0.01) and that of CMV IP 13% (P = 0.07). Ganciclovir appears to reduce the incidence of CMV infections in allogeneic marrow transplant recipients even in those given immune suppressive regimens associated with adequate control of acute graft-versus-host disease.

Acute Disease

Borderline increases in albumin excretion rate and the relation to glycemic control in subjects with type I diabetes.

We evaluated "borderline" increases in overnight albumin excretion rates (AERs)----i.e., those between the upper 95th percentile of normal (7.6 micrograms/min) and the lowest value currently considered predictive of nephropathy (30 micrograms/min)----to determine their importance and to see whether glucose control influenced subsequent changes in the "borderline" AER values. Between 1985 and 1990, we studied 190 subjects with insulin-dependent diabetes mellitus (Type I), analyzing a mean of 6.5 timed overnight urine samples collected per subject. Above-normal AERs were associated with a significantly (by ANOVA) higher mean age (P = 0.03), longer duration of diabetes (P = 0.0002), and greater mean glycohemoglobin values (P = 0.002). The transition rate between borderline and abnormal AERs was significantly higher (P less than 0.0001, chi-square test) than the direct transition rate between normal and abnormal AERs, thus showing the borderline AER to be a definite intermediate stage. Good and poor glucose control were clearly associated with improvement and worsening, respectively, of the borderline AER values (P = 0.032, chi-square test of trend). More attention to borderline AER values is clearly indicated.

Adolescent

Bone marrow transplantation for childhood acute lymphoblastic leukaemia after marrow relapse.

Children with acute lymphoblastic leukaemia in whom relapse in bone marrow occurs have a poor outlook when treated with chemotherapy alone. Twenty-seven patients with childhood acute lymphoblastic leukaemia were treated for marrow relapse with high-dose chemotherapy with or without total body irradiation followed by bone marrow transplantation (BMT). Twenty patients received allogeneic marrow from partially or completely matched histocompatible donors. In this group, nine patients (45%) were free of disease with a median follow-up of 57 months (range, 22 to 126 months) after transplantation, four (20%) died from interstitial pneumonitis and seven (35%) died after a further relapse. Seven patients received autologous marrow collected while they were in remission. In this group, one patient died from infection and six died after a further relapse. We conclude that allogeneic BMT is more effective than autologous transplantation and results in long-term disease-free survival in a significant number of patients. New methods are needed to eradicate residual disease in the patient and to purge marrow ex vivo.

Actuarial Analysis

The use of the Markov process in describing the natural course of diabetic retinopathy.

The natural course of early diabetic retinopathy in young subjects with insulin-dependent diabetes mellitus was evaluated during 693 patient visits for 259 subjects during a mean of 2.4 years. Diabetic retinopathy is considered a progressive disease among people with insulin-dependent diabetes mellitus (type I). Improvement of early retinopathy has not been recognized as a part of the natural course. In our experience, 25% of observations in subjects with early diabetic retinopathy (grades 2 and 3) showed improvement. Thus, 28 of 174 observations of diabetic retinopathy improved from grade 2 to grade 1, and 34 of 79 observations improved from grade 3 to grades 2 or 1. Markov chains indicate that 25% of observations of diabetic retinopathy will change from grade 1 to grade 5 or 6 in 17.0 years and 25% will change from grade 2 to grade 5 or 6 in 16.0 years. Future studies of diabetic retinopathy should consider a matrix of estimated transition probabilities, depending on the population, to judge probabilities of transition between states of retinopathy.

Adolescent

Vitreous fluorophotometry in insulin-dependent diabetes mellitus. Correlation with microalbuminuria and diastolic blood pressure.

Vitreous fluorophotometry was performed on 240 eyes of 120 young subjects who had insulin-dependent diabetes mellitus (type I) and various grades of retinopathy. The concentration of fluorescein was measured in the anterior chamber and posterior vitreous 1 hour after intravenous injection of fluorescein. There was a significant association (P less than .001) between the grade of retinopathy and the level of posterior vitreous leakage. The amount of posterior vitreous leakage in each eye also had a significant association with borderline elevation of diastolic blood pressure. Subjects with excessive posterior vitreous leakage had significantly higher levels of urinary microalbumin excretion. In a multiple linear regression analysis for posterior vitreous leakage, retinal grade consistently entered the model at a significant level (P less than or equal to .00001 to .003). Blood pressure also entered the model for posterior vitreous leakage at a significant level for retinal grades of the right and left eyes and of the worst eye. These results demonstrate an association between leakage of retinal and renal vessels, possibly linked at least in part to elevation in diastolic blood pressure.

Adolescent

Blood pressure and retinopathy in type I diabetes.

The relationship between blood pressure and diabetic retinopathy was evaluated in 249 young subjects with type I diabetes. Although hypertension is known to be associated with an increased risk for retinopathy, the effects of high-normal blood pressure are unknown. Retinopathy (158 of 249 subjects, 63%) is considerably more common in a young diabetic population than is hypertension (7 of 249 subjects, 2%). Thus, if blood pressure is important in the etiology or progression of diabetic retinopathy, levels below the hypertensive range (less than 141/90 mmHg) must be considered. The combined effect of hypertension and high-normal blood pressure (greater than 90th percentile but less than 141/90 mmHg) was studied. Elevation in diastolic blood pressure, alone, and in combination with elevated systolic blood pressure, correlated significantly (P less than 0.03) with retinopathy. The presence of high-normal blood pressure resulted in a prospectively higher occurrence of retinopathy and of progression of preexisting retinopathy. Glycohemoglobin (HbA1) and duration of diabetes also correlated with retinopathy. Both good glycemic control and maintenance of diastolic blood pressure below the 90th percentile for age may be important in relation to diabetic retinopathy.

Adolescent

High-normal blood pressure and early diabetic nephropathy.

The relationship between high-normal blood pressure (BP) levels and early diabetic nephropathy is currently unknown. Blood pressure levels were checked longitudinally for a mean of 6.6 years in 230 subjects to determine their relationship to early diabetic nephropathy as monitored by microalbuminuria. High-normal BP level correlated with the presence of microalbuminuria. Microalbuminuria was 2.8 times as common in subjects with high-normal BP levels compared with those subjects with BP levels below the 90th percentile for their age. The elevated microalbumin excretion was primarily associated with high-normal diastolic BP levels. Our data suggest that either microalbuminuria or high-normal BP levels can precede the other. In a logistics model, diastolic BP and mean HbA1 (over 6.6 years) entered the model at similar levels, followed by duration of diabetes. When the influence of mean HbA1 was removed using logistic regression, the diastolic BP level remained a significant associated factor for the presence of microalbuminuria.

Adolescent

Effects of storage time and temperature on measurement of small concentrations of albumin in urine.

Accurate measurement of albumin excretion rates is important in choosing treatment regimens that may reverse early diabetic renal damage. We report here determinations of slight albuminuria ("microalbuminuria") by radioimmunoassay of fresh specimens, frozen aliquots (stored at -20 degrees C for two, eight, and 24 weeks), and refrigerated specimens (stored at 4 degrees C for one, two, and eight weeks). Seven separate analyses were performed on 101 specimens of urine obtained from 37 subjects with insulin-dependent diabetes mellitus and from 10 nondiabetic healthy controls of a similar age. Storage of urine samples at -20 degrees C resulted in significantly lower measurements of microalbuminuria than in fresh urine (ANOVA, corrected for repeated measures: P = 0.01 to 0.0001). In contrast, storage of urine samples at 4 degrees C for as long as eight weeks did not significantly affect urinary albumin results. The pH values of the specimens were minimally altered and were not a likely cause of the decreased albumin values in the frozen specimens. We conclude that urine specimens for microalbuminuria measurements should either be analyzed as fresh specimens or stored at 4 degrees C and assayed as soon as possible.

Adult

Antiemetic therapy for chemotherapy-induced vomiting: metoclopramide, benztropine, dexamethasone, and lorazepam regimen compared with chlorpromazine alone.

Twenty-six children aged 4 to 15 years who were to receive cancer chemotherapy were enrolled in a double-blind, randomized, crossover trial that compared the antiemetic efficacy of a four-drug regimen (the MBDL regimen: metoclopramide, 8 mg/kg; benztropine, 0.04 mg/kg; dexamethasone, 0.7 mg/kg; lorazepam, 0.1 mg/kg), given over 24 hours, with the efficacy of chlorpromazine, 3.3 mg/kg, given in four doses over 24 hours. The MBDL regimen was more effective than chlorpromazine in both objective and subjective measures of antiemetic control. Of 26 children, 23 (89%) had less vomiting on the MBDL regimen, and 20 (77%) of 26 patients or parents preferred this regimen (p less than 0.01). The MBDL regimen reduced the number of vomiting episodes by a mean of 4.0 (p less than 0.01) and reduced the duration of vomiting by a mean of 3.7 hours (p less than 0.01). A moderate level of sedation was documented at some stage in the 24-hour period of observation in 27% on the MBDL regimen and in 35% receiving chlorpromazine. Dystonia was seen in 1 (4%) of 26 children. We conclude that the MBDL regimen is safe in children and more effective than chlorpromazine.

Adolescent

Orchiopexy: an experimental study of the effect of surgical technique on testicular histology.

Orchiopexy was performed in 35 mature Sprague-Dawley rats using absorbable suture, nonabsorbable suture or a classical dartos pouch technique without suture fixation. Examination of the chromic-fixed testes revealed severe acute inflammation of the suture site and most of the parenchyma in 76 per cent, with abscess formation in 65 per cent, complete absence of spermatogenesis in 82 per cent and evidence of tubular necrosis in 88 per cent. Nylon-fixed testes were adherent only at the sutures, with absent spermatogenesis in 29 per cent, moderate to severe tubular necrosis in 29 per cent and tubular atrophy in 58 per cent. Dartos-fixed testes demonstrated complete circumferential adherence, normal spermatogenesis in 94 per cent and minimal focal tubular atrophy in 23 per cent. Contralateral testes appeared normal in all animals.

Animals

The natural history of medication compliance in a drug trial: limitations of pill counts.

To assess medication compliance over time, we prospectively performed pill counts among 121 ambulatory hypertensive subjects for less than or equal to 12 months. Prescribed regimens consisted of pinacidil or hydralazine administered four times a day and of secondary drugs administered up to twice daily. Surreptitious pill counts occurred every 1 to 12 weeks. Among a middle-aged subject group that had been selected for high rates of compliance, we observed mean compliance rates that approximated 100%. We noted marked intrasubject and intersubject variability for any one medication, between medications, and over time. From baseline blood pressures (+/- SE) of 155.5 +/- 1.9/97.3 +/- 1.0 mm Hg, subsequent mean blood pressures varied by compliance subgroup: "hypocompliers" (less than 80%), 151.3/91.0 mm Hg; "hypercompliers" (greater than or equal to 120%), 147.6/91.4 mm Hg; and "eucompliers" (80% to 119%), 143.3/88.5 mm Hg (systolic blood pressure: F1,52 = -220.9, NS; diastolic blood pressure: F1,52 = -121.4, NS). We concluded that weekly pill counts indicated marked intersubject and intrasubject variability, obscured by long-term averages; that compliance lapses appeared to be random; and that excessive medication-taking was the most consistent with "pill dumping."

Antihypertensive Agents

Arrhythmogenic right ventricular dysplasia in a child with congenital enteropeptidase deficiency and hypogammaglobulinaemia.

A case of arrhythmogenic right ventricular dysplasia in a 10 year old girl is described which provides some evidence for an inherited aetiology of this unusual form of heart disease. The parents of this child were first cousins, thus increasing the possibility of inherited disorders in their offspring. She had been known from infancy to have the rare disorder of congenital deficiency of intestinal enteropeptidase, and low serum immunoglobulins G and A. An untyped adenovirus was grown from a myocardial biopsy taken early in the course of her cardiac disease. However, it is unlikely that this virus was a major factor in the aetiology of her cardiac disease. Both the cardiac and intestinal diseases are now commonly believed to result from hereditary factors, and this report provides further support for this view.

Agammaglobulinemia