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Biomedical subjects

J Higginson

Publications and source records attributed to J Higginson.

At least 19 recordsLinked to original sources
PubMed1995

The acute phase protein response in patients receiving subcutaneous IL-6.

IL-6, tumour necrosis factor-alpha (TNF-alpha) and IL-1 are thought to be the key mediators of the acute phase response although much of the evidence is based on in vitro studies. It is not clear to what extent each of the acute phase proteins are regulated in vivo by each of these cytokines. The aim of this study was to examine the effects of IL-6 treatment in eight patients with cancer on the concentrations of an extensive range of positive and negative acute phase proteins. It was part of a larger investigation to assess the value of IL-6 in the management of chemotherapy-induced thrombocytopenia. IL-6 was administered by a daily subcutaneous injection for 7 days at a dose level of 1, 3, or 10 micrograms/kg/day. Increases in the positive acute phase proteins, serum amyloid A, C-reactive protein, alpha 1-acid glycoprotein, alpha 1-antichymotrypsin, haptoglobin, alpha 1-antitrypsin, fibrinogen, complement component C3, and caeruloplasmin, were observed, with the greatest incremental changes and fastest responses being seen for C-reactive protein and serum amyloid A protein. The negative acute phase proteins transferrin, transthyretin and retinol binding protein all fell to a nadir within 48-96 h after the first IL-6 injection. Increases in complement component C4 were only found in two patients, which may be related to the increase in circulating TNF-alpha concentrations found only in these patients. This study has therefore shown that IL-6 is capable of causing changes in the majority of acute phase proteins in vivo. Although secondary induction of TNF-alpha was not observed in the majority of patients examined, it is still possible however that other cytokines involved in regulation of the acute phase response, such as IL-1, may have been induced and contributed to the overall response.

Acute-Phase Proteins↗
PubMed1994

A prospective study of the prevalence of clear-cut endocrine disorders and polycystic ovaries in 350 patients presenting with hirsutism or androgenic alopecia.

OBJECTIVE: To determine the frequency of polycystic ovaries (PCO) on ultrasound and the incidence of clearcut endocrine disorders leading to virilization in patients complaining of hirsutism or androgenic alopecia. The major purpose was to determine a coherent policy for the routine biochemical assessment of such women. DESIGN: A prospective study of women attending a joint skin/endocrine clinic complaining of these problems. PATIENTS: Three hundred and fifty consecutive women with hirsutism and/or androgenic alopecia were assessed. MEASUREMENTS: Baseline endocrine screens were conducted on two occasions and included measurement of serum testosterone, androstenedione, dehydroepiandrosterone sulphate, sex hormone binding globulin, LH, FSH, 17-hydroxyprogesterone and PRL. The ovaries were visualized by high-resolution pelvic ultrasound scanning. RESULTS: Eight women were identified with relevant endocrine disorders; of these, one was acromegalic and one had a microprolactinoma--in both cases the association may have been fortuitous. Three had clear-cut 21-hydroxylase deficiency, one a rare hepatic enzyme deficiency (11-reductase), one a virilizing adrenal carcinoma and one a Leydig cell tumour. The latter six cases all had persistently elevated levels of serum testosterone (> 5 nmol/l). In all, 13 women had baseline testosterone levels in excess of 5 nmol/l. Polycystic ovaries were present in 81% of the cases who had erratic cycles and 52% of those with regular cycles; PCO were present in two of the women with 21-hydroxylase deficiency and in the woman with 11-oxoreductase deficiency. The Leydig cell tumour (1.2 cm diameter) was not detected on ultrasound or CT scan. CONCLUSIONS: For the exclusion of enzyme deficiencies and virilizing tumours clinical assessment and a single serum testosterone measurement will suffice.

Adult↗
PubMed1992

Abdominal irradiation in childhood; the potential for pregnancy.

OBJECTIVE: To investigate the impact of premature ovarian failure due to whole abdominal radiotherapy (DXT) in childhood on uterine physical characteristics and blood flow and measuring the uterine response to exogenous sex steroid replacement. DESIGN: A comparative observational study SUBJECTS: 10 women with premature ovarian failure due to treatment with whole abdominal irradiation in childhood. A comparison group of 22 women with premature ovarian failure who had not received whole abdominal DXT. MAIN OUTCOME MEASURES: Uterine length and uterine blood flow measurement plus serial assessment of endometrial thickness during a cycle of exogenous sex steroid replacement. RESULTS: Uterine length was significantly less (P less than 0.01) in women who had been exposed to whole abdominal DXT in childhood (mean 4.1 cm, 2SE 0.8) compared with a mean of 7.3 cm (2SE 0.6) in the comparison group. The three women in the DXT group who were studied serially had no increase in endometrial thickness in response to physiological sex steroid replacement therapy and most of the 10 irradiated women had no detectable uterine blood flow with Doppler ultrasound. CONCLUSIONS: Uterine musculature and blood flow are irreversibly affected by high dose irradiation in childhood. Non-invasive assessment of this nature may predict potential for pregnancy following ovum donation and embryo transfer.

Adult↗
PubMed1991

Restricted electrophoretic heterogeneity of immunoglobulin light chains in urine: a cause for confusion with Bence Jones protein.

The detection of Bence Jones protein, an important part of the investigation of suspected myeloma, is most commonly done by agarose or cellulose nitrate electrophoresis followed by immunofixation. Bence Jones protein is recognized as single or multiple bands of one type of light chain. Unfortunately, improvements in sensitivity of these techniques (use of high-affinity antisera and higher resolution electrophoresis) frequently allow detection of multiple light chain bands in the urine of patients who do not have a B-cell dyscrasia. The bands are usually kappa, although they may be accompanied by lambda bands. This pattern may lead to the misdiagnosis of Bence Jones protein and oligoclonal light chain production in patients. Here we show that this pattern is produced by polyclonal light chains; it is present in the urine of all patients with a tubular proteinuria of any etiology and may be induced in healthy individuals by blocking their renal tubular protein reabsorption. Polyclonal light chains separate into monomers and dimers on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and into four major bands with many minor bands by isoelectric focusing. This difference in charge and possibly size results in the banding pattern seen on good-quality electrophoresis and immunofixation.

Aged↗
PubMed1989

The value of C-reactive protein in the diagnosis of intestinal perforation in typhoid fever.

Serum C-reactive protein concentrations were measured in 28 Nigerian patients with typhoid fever on presentation at hospital and at intervals thereafter. Five of the 28 (18%) were subsequently diagnosed as suffering from ileal perforation. These patients had concentrations of C-reactive protein during the first 24 h of admission which were significantly higher (mean = 229 mg/L) than those without perforation (mean = 91 mg/L). C-reactive protein may have a role in the prediction of early diagnosis of perforation in patients with typhoid fever.

C-Reactive Protein↗
PubMed1988

Changing concepts in cancer prevention: limitations and implications for future research in environmental carcinogenesis.

While the cause and nature of certain human cancers are known, definitive preventative guidelines still cannot be offered for many types of tumors. This is partly due to the inherent biostatistical and epidemiological limitations involved in the identification and interpretation of complex carcinogenic risk factors and potential low-risk hazards. Two divergent control strategies have emerged: (a) regulatory programs designed to control or eliminate minute quantities of pollutants in the ambient environment, based on fairly rigid quantitative risk assessment; (b) a biological research effort to understand the fundamental biological mechanisms with the objective of eventually manipulating or intervening in carcinogenesis through chemoprevention or therapy. Apart from more intensified effort on certain already recognized causal factors, current research indicates that the eliminatory approach will have little impact on the cancer burden and that the mechanistic approach, although difficult and slow, represents the most logical alternative. This will require long-term major investments in fundamental research and manpower. This biological approach, however, is largely ignored by the public and legislative bodies concerned with cancer control strategies, partly due to lack of formal input to appropriate national bodies by experts in chemical carcinogenesis. Informed scientists have an important role in ensuring that the public and legislative bodies are aware of current scientific views on carcinogenesis and the need to establish priorities in research.

Carcinogens, Environmental↗
PubMed1987

Everything is a carcinogen?

The public has developed the impression that in an industrialized society environmental carcinogens are ubiquitous and that all chemical exposures, irrespective of the dose, influence carcinogenesis. Such impressions are influenced by many nonscientific considerations and often reflect insufficient knowledge of scientific data and methods. Such misconceptions are thus partly explained by the multistage nature of carcinogenesis, the absence of a clear understanding, and definition of the multiple factors which influence cancer induction. It is obvious that not all chemicals are carcinogenic and it is reasonable to accept that not all substances (including primary chemical carcinogens) that are found to enhance carcinogens in animals are necessarily carcinogenic to humans under conditions of usual human exposure.

Animals↗
PubMed1985

Acute phase response of serum amyloid A protein and C reactive protein to the common cold and influenza.

C reactive protein (CRP) and serum amyloid A protein (SAA) are sensitive and rapid acute phase reactants, and their measurement for monitoring inflammatory disease and assessing the prognosis in secondary amyloidosis is gaining widespread acceptance. The changes in these proteins in eight subjects suffering from natural colds, 15 subjects with experimentally induced colds (rhinoviruses E1, 3, 9, 14, or 31), and eight with experimentally induced influenza (A/Eng/40/83) were studied. SAA concentration increased in 21 of the 23 subjects with natural or experimental rhinovirus colds (mean increase 95 mg/l); CRP concentration increased in 11 (mean increase 11 mg/l). All subjects with influenza showed pronounced increases in SAA concentrations (mean increase 642 mg/l) while six showed increases in CRP concentration (mean increase 22 mg/l). All these increases were highly significant (p less than 0.001). Asymptomatic excretors of both rhinovirus and influenza virus showed significant increases in SAA concentration (p = 0.015 for rhinovirus and p less than 0.001 for influenza virus) but not in CRP concentration. No changes in SAA or CRP values were seen in 12 volunteers after challenge with saline. These observations suggest that caution is required in the interpretation of estimations of SAA concentration and that it may be too sensitive an acute phase protein for clinical use as its concentration may be raised in both trivial and asymptomatic viral infections.

Amyloid↗
PubMed1985

Cancer risk factors in human studies.

The historical developments leading to the acceptance of the influence of dietary and behavioral aspects of our life-style on cancer are reviewed. However, present information is usually insufficient to permit description of the complex mechanisms involved that are unlikely to yield to classical epidemiologic approaches alone. Better integrated laboratory epidemiologic studies are required that use more advanced nonintervention techniques. Progress may be slow in the identification of such factors in view of the many parameters involved, the absence of a single predominant or avoidable cause in many cancers, and the lack of adequately developed laboratory techniques for epidemiologic application.

Behavior↗
PubMed1985

DDT: Epidemiological evidence.

The use of DDT as a pesticide, until its banning in many countries, is reviewed briefly. The tissue levels of DDT can be regarded as an index of past exposures, and findings in several countries are described. It is emphasized that insufficient case-control studies are available for evaluation and that assessment of the potential carcinogenic effects of DDT in humans is largely dependent on inferences from descriptive epidemiology. DDT is a non-genotoxic carcinogen in animals and a mild hepatoxic agent. The liver is a probable target organ in man. No correlation at the population level can be demonstrated between exposures to DDT and the incidence of cancer at any site. It is concluded that DDT has had no significant impact on human cancer patterns and is unlikely to be an important carcinogen for man at previous exposure levels, within the statistical limitations of the data.

Adipose Tissue↗