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Biomedical subjects

J Duffy

Publications and source records attributed to J Duffy.

At least 91 records · Page 5Linked to original sources

Stability of interleukin 1 beta (IL-1 beta) in aqueous solution: analytical methods, kinetics, products, and solution formulation implications.

The thermal stability of IL-1 beta in aqueous solution as a function of temperature (5-60 degrees C), pH (2-9), buffer (acetate, citrate, tris, and phosphate), and cyroprotectants (sugars, HSA) was investigated in this study. The analytical methodologies included RP-HPLC, SEC, ELISA, IEF-PAGE, SDS-PAGE, and bioassay. The degradation and inactivation of IL-1 beta at or above 39 degrees C were attributed to autoxidation of the two cysteine residues in the denatured protein, followed by hydrophobic/covalent aggregation and precipitation. At or below 30 degrees C, IEF- and SDS-PAGE results suggest a possible deamidation reaction. The difference in mechanism of degradation precludes the prediction of formulation shelf life from accelerated temperature data. Nonetheless, the good stability observed at 5 degrees C suggests that a solution formulation may be feasible for IL-1 beta.

Drug Stability↗

A sibling-controlled study of intelligence and academic performance following Reye syndrome.

The authors compared the intellectual, cognitive and academic abilities of 22 survivors of Reye syndrome attending normal schools with the sibling nearest in age as control. The British Ability Scales, visual and verbal IQ, short-term memory scales and attainment tests were administered to all children. Reye syndrome children as a group differed significantly from the controls only on the basic number skills test. However, children with severe encephalopathy and those whose illness occurred in infancy had significant deficits on many of the tests. 18 children recovered without requiring 'additional educational provision'; the mean IQ of the 22 Reye syndrome children was 101. Nonetheless, these children's poor performance on the basic number skills test has important implications for teachers, and careful monitoring of future educational performance is essential.

Achievement↗

Association of age and social class with suicide among men in Great Britain.

STUDY OBJECTIVE: The aim was to investigate suicide and "undetermined" deaths by age, economic activity status, and social class in Great Britain among males of working age. DESIGN: The study was a cross sectional analysis of Registrar General's data for England and Wales around 1981, repeated for around 1971, and for Scotland around 1971 and 1981. MEASUREMENTS AND MAIN RESULTS: For England and Wales around 1971, suicide and undetermined death rates showed a progressive increase with age and a markedly higher rate in the lower social classes. A significant interaction effect was identified in the central age groups of the lower occupational categories. This interaction was confirmed in the remaining three data sets, notwithstanding some differences in the profile of age specific mortality. Other findings included a higher standardised mortality ratio for the economically inactive, who also showed an earlier peak in age specific mortality, and a relative concentration of undetermined as compared to suicide deaths in the lower social classes, but not all these further results were fully replicated. CONCLUSIONS: There is a concentration of suicide and undetermined deaths in the middle age groups of the lower social classes. Plausible explanations include both the social drift and the social genesis hypotheses, the latter including the effects of long term unemployment.

Adolescent↗

Lyme disease: a clinical review.

Lyme disease is caused by the spirochete Borrelia burgdorferi, which is transmitted primarily by Ixodes dammini ticks in the Northeast and Upper Midwest, by Ixodes pacificus in Western states, and by Ixodes ricinus in Europe. Lyme disease can affect the skin, nervous system, heart, eyes, and joints, and is diagnosed in patients with these characteristic clinical features: exposure to an endemic area and usually a positive serologic test for B. burgdorferi six or more weeks after infection. Full recovery is possible with early diagnosis and treatment.

Animals↗

The clinical spectrum of the eosinophilia-myalgia syndrome associated with L-tryptophan ingestion. Clinical features in 20 patients and aspects of pathophysiology.

We describe the clinical spectrum of the L-tryptophan-associated eosinophilia-myalgia syndrome in 20 patients. In all but one case, patients met the Centers for Disease Control (CDC) case definition for the syndrome: peripheral blood eosinophilia (eosinophil count greater than 1.0 x 10(9)/L) and generalized, disabling myalgias without other recognized causes. Three patients with eosinophilia and myalgia developed eosinophilic fasciitis, and 4 other patients developed, respectively, pneumonitis and myocarditis, neuropathy culminating in respiratory failure, encephalopathy, and fibrosis about the common bile duct. No relation was apparent between dose or duration of L-tryptophan exposure and the eosinophilia-myalgia syndrome. No organic contaminants were identified in L-tryptophan preparations taken by patients or asymptomatic users when these preparations were examined by chromatography or mass spectroscopy. Biopsy specimens in 12 patients showed a mononuclear exudate with a variable admixture of eosinophils in affected tissues, including skin, fascia, muscle, and some viscera. Eosinophil toxic granule proteins, major basic protein, and eosinophil-derived neurotoxin were elevated in the serum and urine of patients compared with normal control subjects (P less than 0.01 and P less than 0.02, respectively). Immunofluorescence showed major basic protein deposited outside of eosinophils in affected tissues, indicating that toxic granule proteins are released in diseased organs. Treatment included withdrawal of L-tryptophan in all cases. Corticosteroids were prescribed for 16 patients and diuretics alone for 1 patient; no drugs were prescribed for 3 patients. Four patients have recovered fully, others are stable or slowly recovering, and 1 is gravely ill despite prolonged treatment.

Adult↗

French influence on the development of medicine in Louisiana.

The paper presents a brief survey of the state of medicine in the 18th century with an emphasis upon developments in France. In the early nineteenth century the emergence of the Paris Clinical School made France pre-eminent in medicine. Its leaders emphasized localism, correlated symptoms with postmortem reports, and introduced clinical statistics. They also introduced the stethoscope and the techniques of auscultation and palpation and were the first to recognize that excessive bloodletting, purging and other depletory measures were harmful. The French population in Louisiana continued to look to France for educational and intellectual leadership well into the nineteenth century, and the findings of the Paris Clinical School had an immediate impact upon Louisiana medicine, leading to a clash between the French-speaking physicians who emphasized moderation and good nursing and the English-speaking practitioners who believed in drastic intervention.

Clinical Medicine↗

Absolute and relative perceptual codes in young children.

Three experiments were conducted to ascertain whether young children's perceptual codes, as evidenced by choice reaction times, were related to either the absolute difference or the ratio between stimuli. In Experiments 1 and 2, children were shown pairs of line lengths and were asked to choose either the longer or shorter line within each pair. In Experiment 3, children chose which of two birds on a map was closer to themselves or to the experimenter. In all three experiments, children's reaction times were related to both the absolute differences and ratios between pairs of stimuli. The findings suggest that perceptual judgments in young children may be based on both absolute and relational codes.

Attention↗

Lyme disease.

Lyme disease is a complex multisystem disorder recognized on six continents that is epidemic in some parts of the world during spring, summer, and fall seasons. It is an infectious disease caused by a spirochete, B. burgdorferi, which is transmitted chiefly by I. dammini and pacificus ticks in the United States and I. ricinis in Europe. It is a disease with early and late cutaneous manifestations plus involvement of the nervous system, heart, eye, and joints in variable combinations. Diagnosis is based on patient contact with an endemic area, one or more characteristic clinical features, particularly erythema migrans rash, and a positive serologic test for B. burgdorferi infection in the majority of cases with illness greater than 4 to 6 weeks' duration. Although infection is the primary cause, immune mechanisms almost certainly play a synergistic role in some manifestations during late stages. Prompt diagnosis and treatment are important for full recovery. Therapy with doxycycline or amoxicillin is effective in the earliest stages but serious late complications require high doses of intravenous penicillin or ceftriaxone. Some sequelae respond well to antibiotic therapy while others such as chronic arthritis or advanced central nervous system disease may not. Anti-B. burgdorferi antibodies appear to be protective in certain experimental studies but data are limited and inconclusive in humans.

Animals↗

Development and characterization of a lyophilized dosage form of IL-1 beta.

The development and characterization of a lyophilized dosage form for recombinant Interleukin-1 beta is described. Included in the evaluation of the drug product are accelerated and long-term stability studies utilizing a number of biophysical techniques (reverse-phase HPLC, SDS-PAGE, isoelectric focusing and ELISA). Data collected with these methods were examined for correlations with biological activity assessments provided by an in-vitro cell culture system (mouse thymocyte proliferation). Results of these studies demonstrate that a lyophilized dosage form of Interleukin-1 beta can be prepared which retains its potency for at least 1 year when stored at ambient temperature. The analytical methodology used to assess the physicochemical integrity of the protein provided a sensitive and reproducible means of predicting changes in biological activity.

Animals↗

Alcohol consumption, cigarette sales and mortality in the United Kingdom: an analysis of the period 1970-1985.

This paper examines official published statistics for various causes of death in the United Kingdom between 1970 and 1985. The variables selected were mainly those that had been linked to alcohol or cigarette use. In particular, changes in mortality due to acute myocardial infarction, cancer of trachea, bronchus and lung, cirrhosis of the liver and 'alcoholism' were found to be associated with each other. Changes in all of these were highly associated with changes in both alcohol consumption and cigarette sales. For most of the causes of death examined, correlations were higher for changes in the current year than they were for lagged data. Thus even chronic disorders related to prolonged heavy alcohol or tobacco use appear to be influenced rapidly by shifts in general levels of drinking and smoking.

Alcohol Drinking↗

Changes in food intake and activity after quitting smoking.

Quitting smoking often results in weight gain. The causes of the gain are not known. The present study evaluated changes in calories, total sugars, sucrose, fat, protein, and nonsugar carbohydrates as well as changes in activity levels after quitting smoking. Ninety-five subjects were randomly assigned to either early (Week 2) or late (Week 6) quit dates. Subjects were assessed on weight, food intake, activity levels, and smoking levels at baseline, at Weeks 4 and 8, and at Weeks 12 and 26 postquit. The results indicated significant increases in calories, sucrose, and fats 2 weeks after the quit date. Changes for total sugars were less consistent. Activity levels did not change significantly. Early caloric increases predicted weight gain at 26 weeks for abstinent women. No relation was found for abstinent men, but interpretation of this finding is weakened by a small subsample size. Abstinent subjects gained over 9 lb by 26 weeks postquit. Despite this gain, Week 26 results showed that caloric intake for abstinent women was approximately equal to that observed at baseline, whereas that for abstinent men had dropped significantly.

Adult↗

Alcoholic and non-alcoholic liver disease in relation to alcohol consumption in Scotland, 1978-84. Part I: Epidemiology of liver diseases.

A common strategy in epidemiological studies linking alcohol consumption in the general population with liver cirrhosis mortality is to use non-specific cirrhosis mortality rates in which alcoholic and non-alcoholic causes of death are not distinguished. Evidence is presented from Scottish mortality data for 1979 to 1984 that the two forms of cirrhosis have quite different epidemiological profiles. Similar findings emerge from morbidity data. The two forms of disease should be distinguished in future studies in which liver cirrhosis is used as a proxy for consumption, despite the manifest shortcomings of currently available data.

Adult↗

Reducing smoking among pregnant adolescents.

Pregnant adolescents who smoke present a double obstetrical risk. Not only is the adolescent mother at risk from the biological, social, educational, and economic factors associated with childbearing at a young age, she and her developing infant also risk the complications associated with maternal smoking. This paper describes a psychosocial intervention designed to reduce smoking in a group of pregnant adolescents. Five modules are presented. Each is designed to: (1) heighten awareness of the issue, (2) provide motivational messages, (3) enhance the adolescent's social skills, and (4) teach specific smoking-cessation skills.

Adolescent↗

Eosinophilia associated with perimyositis and pneumonitis.

We describe a patient who had severe myalgias, bronchial asthma, pulmonary infiltrates, and eosinophilia. The findings on physical examination and the erythrocyte sedimentation rate were normal; there was no elevation of the serum creatine kinase. Muscle biopsy demonstrated an inflammatory exudate that contained eosinophils, localized primarily to the perimysium. Pulmonary and muscle manifestations responded to corticosteroids. Systemic eosinophilic disease associated with perimyositis or myositis has not been reported previously. In addition, we review the spectrum of eosinophilic muscle diseases--eosinophilic perimyositis, eosinophilic polymyositis, and focal eosinophilic myositis.

Biopsy↗

Diagnosing Lyme disease: the contribution of serologic testing.

Lyme disease is a multisystem disorder caused by a tick-transmitted spirochete, Borrelia burgdorferi. The diagnosis is based on clinical findings in most patients, particularly those with erythema migrans or exposure to geographic locations endemic for the disease. Detection of a specific antibody to B. burgdorferi is a useful confirmatory test in many patients. In atypical cases, however, a positive test result can be pivotal for determining the diagnosis and can lead to institution of definitive treatment. Serologic testing should not be used indiscriminately to diagnose Lyme disease or as the sole basis for administration of antibiotic therapy.

Aged↗

Suppression of postprandial glucose, insulin, C-peptide, and glucose-dependent insulinotropic peptide (GIP) in man by oral administration of a prostaglandin analogue (enprostil).

Enprostil, a long-acting, orally active dehydroprostaglandin E2 with cytoprotective and gastric antisecretory properties, is a potent inhibitor of meal-stimulated gastrin release. Recent data have suggested suppression of additional other gastrointestinal peptide hormones following single doses of enprostil. The current investigation was conducted to further clarify the effects of enprostil administration on gastrointestinal hormones and glucose metabolism under physiologic conditions and to determine whether these effects were present following multiple doses of the agent. Enprostil 70 mcg/d and its placebo were each administered for 7 1/2 days to eight normal male subjects in a study of crossover design, each treatment period lasting 7 1/2 days and separated by a 7 day washout period. Subjects received a test meal on days 1 and 8 and an oral glucose challenge on day 3 of each treatment period following enprostil or its placebo. Following the test meal, there was a delay and suppression of the maximum measured serum glucose levels. Mean overall peak glucose concentrations were lower during the enprostil phase compared to placebo (112 vs. 121 mg/dd, P = 0.025) with a trend toward delay in the time to achievement of peak glucose concentrations. Mean overall peak levels for insulin, C-peptide, and glucose-dependent insulinotropic peptide (GIP) were significantly suppressed by 36%, 16% and 60%, respectively by enprostil when compared to placebo. The overall integrated postprandial responses for insulin, C-peptide, and GIP were significantly reduced by 42%, 39% and 90%, respectively while that for glucose above baseline was reduced by 44% (P = 0.098). Similar effects were present following the oral glucose challenge.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

The antihypertensive efficacy of nifedipine alone and in combination in general practice.

A multi-centre study in general practice involving 3242 hypertensive patients, aged up to 70 years, was carried out to evaluate the efficacy and tolerability of nifedipine used alone or in combination with other antihypertensive agents in step-care treatment. Patients were treated for up to 8 weeks with one of four regimens: nifedipine monotherapy; diuretic and nifedipine; beta-blocker plus nifedipine; and nifedipine added to a combination of diuretic and beta-blocker. All patients received 20 mg nifedipine, in slow-release tablet form, twice daily; at Week 4, dosage was increased to 40 mg twice daily in 8.5% patients because their supine diastolic blood pressure still exceeded 95 mmHg. Changes in mean blood pressure of the total study group for systolic and diastolic, supine and standing, were highly significant both from baseline (Week 0) to Week 4 (p less than 0.0001) and from baseline to Week 8 (p less than 0.0001). Mean blood pressure reduction was 29/18 mmHg supine and 27/18 mmHg standing. Statistical differences in blood pressure response between age, sex and treatment groups were not of clinical significance. Statistically significant reductions in heart rate (mean 1.9 beats/min, p less than 0.001) and body weight (mean 0.48 kg, p less than 0.001) were noted, but were not of clinical relevance. Nifedipine produced a net increase of 12% in side-effects at Week 4 compared to the profile at entry.

Adult↗