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Biomedical subjects

G Russell

Publications and source records attributed to G Russell.

At least 19 recordsLinked to original sources

Immunohistochemical evidence that Met-enkephalin and GABA coexist in some neurones in rat dorsal horn.

A pre-embedding immunohistochemical method to detect Met-enkephalin was combined with postembedding immunohistochemistry with GABA and glycine antisera, in order to determine whether or not Met-enkephalin coexisted with either of these inhibitory transmitters in neuronal cell bodies within the superficial dorsal horn of the rat. The distribution of immunostaining with the three antisera was similar to that which has been described previously. Of 74 enkephalin-immunoreactive neurones in laminae II and III, 51 were immunoreactive with the GABA antiserum and 23 were not. All of the neurones which were not GABA-immunoreactive were located in lamina II. None of the enkephalin-immunoreactive cells showed glycine-like immunoreactivity. These results suggest that enkephalin is present both in GABAergic neurones and in neurones which do not contain GABA within the rat superficial dorsal horn. It is likely that the population of neurones immunoreactive with both enkephalin and GABA antisera includes lamina II islet cells and that the population which were enkephalin-immunoreactive but not GABA-immunoreactive includes stalked cells. In addition, this latter group may correspond to those cells which possess both enkephalin- and substance P-like immunoreactivity and which have been described previously in this area.

Animals

Respiratory symptoms and atopy in Aberdeen schoolchildren: evidence from two surveys 25 years apart.

OBJECTIVE: To estimate changes in the prevalence of respiratory symptoms and the reported diagnoses of asthma, eczema, and hay fever in primary school children in Aberdeen between 1964 and 1989. DESIGN: Determination of incidence prevalence and prevalence from survey data. SETTING: Aberdeen, Scotland. PARTICIPANTS: 2743 primary school children (aged 8-13) from 1964 and 4003 [corrected] from 1989. MAIN OUTCOME MEASURES: Survey data on whether, according to the parent or guardian, the child wheezed or was troubled with shortness of breath; the number of episodes of breathlessness in the past year; and whether asthma, eczema, or hay fever had ever been diagnosed. RESULTS: Questionnaires were completed by the parents of 2510 children in 1964 and 3403 children in 1989. The prevalence of wheeze rose from 10.4% in 1964 to 19.8% in 1989, and the prevalence of episodes of shortness of breath increased from 5.4% to 10.0%. In both surveys wheeze and shortness of breath were more prevalent in boys than in girls. The reported diagnosis of asthma rose from 4.1% to 10.2%, hay fever from 3.2% to 11.9%, and eczema from 5.3% to 12%. The proportion of boys suffering from eczema rose from 47.7% to 60.0%. Hay fever showed a similar increase, from 49.4% to 60.1%, in boys over the 25 year period. Though the parents of a higher proportion of children with wheeze were aware of the diagnosis of asthma in 1989, because of the increased prevalence of wheeze the absolute number of parents of wheezy children who were not aware of a diagnosis of asthma increased from 7.4% to 9.6% of the population studied. CONCLUSION: The higher diagnosis rate for asthma is due not simply to changes in diagnostic fashion but reflects an increase over the past 25 years in the prevalence of respiratory symptoms, which in turn may reflect a more general change in the prevalence of atopy, the increase in which was particularly noticeable in boys. This increase explains some of the increase in hospital admission rates for children with asthma.

Adolescent

Oestradiol inhibits the release of tumour necrosis factor but not interleukin 6 from adult human osteoblasts in vitro.

Oestrogens may control bone remodelling by directly regulating the synthesis of cytokines in osteoblasts. We have investigated the effects of oestradiol on the release of two cytokines, IL-6 and TNF, known to be produced by normal human osteoblast-like cells. The effect of oestradiol on basal and stimulated IL-6 and TNF release was investigated. The concentration of IL-6 and TNF in 24 h bone cell-conditioned medium was determined using bio- and immunoradiometric assays. The results showed that 17 beta-oestradiol (10(-10) and 10(-8) M) inhibited IL-1-stimulated TNF release in a dose dependent manner in 7 out of 9 patients. Maximal inhibition was observed with 10(-8) M 17 beta-oestradiol, producing an average 30% reduction in TNF release. In contrast 17 beta-oestradiol (10(-12)-10(-8) M) failed to consistently regulate basal or stimulated IL-6 release. IL-6 mRNA levels were also shown not to be modulated by 17 beta-oestradiol (10(-9) M) under stimulatory conditions. rhIL-1 alpha (10 U/ml) was a consistent and potent stimulator of IL-6 and TNF release, and the glucocorticoid hydrocortisone was found to be a powerful suppressor of both IL-6 and TNF release under basal or stimulatory conditions. In conclusion direct regulation of bone remodelling by oestradiol does not appear to be effected via the control of IL-6 production in osteoblasts. However, a suppression of osteoblastic TNF release could represent one facet of the control of bone formation and resorption by oestrogens.

Cells, Cultured

Mechanisms of action of cyclosporine and effects on connective tissues.

Cyclosporine is a potent immunomodulatory agent with an increasing number of clinical applications. Its major mode of action is inhibition of the production of cytokines involved in the regulation of T-cell activation. In particular, cyclosporine inhibits the transcription of interleukin 2. Although cyclosporine's major actions are on T cells, there is some evidence that it produces direct effects on other cell types. Its immunosuppressive action is closely linked to its binding of cyclophilin, a member of a family of high-affinity cyclosporine-binding proteins widely distributed in different cell types and in different species. The cyclophilins have been shown to have peptidyl-prolyl cis-trans isomerase enzyme activity that is blocked by cyclosporine. Although this may be a factor in cyclosporine's selective inhibition of cytokine gene transcription, it is still unclear whether inhibition of this activity is the mechanism through which cyclosporine exerts its effects on target cells. The ubiquitous presence of cyclophilins raises the question of why cyclosporine has major effects on T cells. Perhaps the critical proteins affected are transcriptional regulators restricted in their tissue distribution. The effects of cyclosporine on T cells and, directly or indirectly, on connective tissue cells, all of which can produce a range of cytokines, are of interest in relation to the tissue changes that occur in such inflammatory conditions as rheumatoid arthritis.

Animals

Immunocytochemical evidence that GABA and neurotensin exist in different neurons in laminae II and III of rat spinal dorsal horn.

Pre-embedding immunocytochemistry with antiserum to neurotensin was combined with post-embedding immunocytochemistry with GABA antiserum, in order to identify neurotensin- and GABA-containing neurons in laminae I-III of rat spinal dorsal horn. The distribution of cell bodies containing these two compounds was similar to that which has been described previously. None of the 88 neurotensin-immunoreactive neurons which were tested showed GABA-like immunoreactivity, which suggests that GABA and neurotensin exist in different cells in this region. Since both compounds are thought to be present in islet cells, it is likely that there are two neurochemically distinct populations of islet cells in lamina II of rat spinal cord.

Animals

The ranges of insulin response and glucose tolerance in lean, normal, and obese women during pregnancy.

OBJECTIVE: We characterized insulin secretion and glucose disposal in a large unselected group of women, encompassing the full spectrum of glucose tolerance in pregnancy, and related the findings to maternal obesity. STUDY DESIGN: Intravenous glucose tolerance and first-phase insulin response were measured at about 32 weeks' gestation in 690 unselected pregnancies. The women were designated as "lean," "normal," or "obese" on weight-for-height criteria. RESULTS: The distribution of insulin response was bimodal, but there was no corresponding dichotomy in maternal glucose disposal rate. Insulin response was greatest and glucose disposal rate slowest in obese women. In general, "poor" glucose tolerance was associated with relatively low insulin output. It was not possible to identify any cluster of women, obese or otherwise, in whom poor glucose tolerance was specifically associated with an unusually high insulin response. CONCLUSION: The data indicate that the distribution of glucose tolerance in pregnancy is a continuum. Glucose intolerance represents one end of that spectrum and is attributable to insufficient insulin secretion. This relative insufficiency is most frequent with maternal obesity.

Blood Glucose

Markers of bone and collagen breakdown in early inflammatory arthritis.

Inflammatory arthritis has the potential to cause irreversible erosive damage to cartilage and bone. This may occur very early in the course of the disease. At present it is not possible at diagnosis to identify those patients who will develop erosive damage. If this were possible, it would enable aggressive therapy to be targeted to those patients at greatest risk. There is therefore a need for sensitive markers to detect and quantify joint damage at as early a stage as possible. In this chapter we review potential biochemical markers of such damage and assess their clinical usefulness.

Arthritis

Evaluation of mean transit time in children as an indicator of airways obstruction.

Mean transit time was evaluated as a test of pulmonary function in normal and asthmatic children. It was found to be independent of body size and negatively correlated with PEFR, FEV1 and FVC in normal children. Mean transit time was less sensitive in detecting the effects of bronchodilator therapy in asthmatic children than other simpler tests of lung function. The range of normal was so wide that there was no clear demarcation between normal and abnormal. The degree of overlap makes isolated tests of mean transit time of little diagnostic value. It is therefore concluded that mean transit time though it theoretically offers the attractive advantage of being a sensitive indicator of both large and small airways obstruction, is unlikely to play a major part in the routine evaluation of lung function in asthmatic children.

Adolescent

Spontaneous release of interleukin-I and interleukin-6 by peripheral blood mononuclear cells after oophorectomy.

1. We studied the changes in interleukin-1 and interleukin-6 secretion by peripheral blood mononuclear cells from 12 premenopausal women after oophorectomy and seven premenopausal women who had undergone simple hysterectomy. 2. The results showed that 1 month after surgery interleukin-1 secretion increased by 414 +/- 171% (mean +/- SEM) and interleukin-6 secretion increased by 1354 +/- 481% in oophorectomized women, whereas only non-significant fluctuations in the secretion of both cytokines (-9% +/- 29% for interleukin-1 and -31% +/- 19% for interleukin-6) were seen in the women who had undergone simple hysterectomy. The difference between the two groups was significant (P = 0.035 for interleukin-1 and P = 0.003 for interleukin-6). In addition, oophorectomy, but not simple hysterectomy, was followed by significant increases in plasma ionized calcium concentration (P < 0.05), plasma alkaline phosphatase activity (P < 0.01) and plasma osteocalcin concentration (P < 0.02), and a reduction in plasma parathyroid hormone level (P < 0.01). 3. We conclude that ovary ablation may modify cytokine secretion by peripheral blood mononuclear cells. If this phenomenon occurs in the bone microenvironment, it could be important in the loss of bone observed after oophorectomy. However, the possibility of an independent alteration induced by the lack of gonadal hormones but unrelated to bone turnover cannot be excluded.

Adult

Asthma, inhaled corticosteroid treatment, and growth.

To evaluate the effects on growth of inhaled corticosteroid treatment (ICT) and of the quality of control of asthma, height velocity was studied in 58 prepubertal children attending a specialist asthma clinic because of chronic asthma that was difficult to control. The height velocity standard deviation (SD) score was maximal when the asthma was well controlled both before (0.01) and after (-0.07) starting ICT. It was least when the asthma was poorly controlled both before (-1.50) and after (-1.55) starting ICT. The effectiveness of control correlated significantly with the height velocity SD score, both before and after ICT was started. No evidence was found that the administration of ICT has an adverse effect on growth.

Administration, Inhalation

High-dose megestrol acetate as third-line endocrine therapy for metastatic breast cancer.

High-dose megestrol acetate (800 mg/day) was administered to 34 patients as third-line endocrine therapy for metastatic breast cancer after progression on standard-dose megestrol acetate (160 mg/day). Among the 32 evaluable patients, no complete or partial response occurred. Ten patients remained stable and 22 progressed. No patients remained on study. Median time to progression was 2 months (range, 1-13 months). The use of high-dose megestrol acetate did not result in objective responses but may have been effective in delaying progression in one third of patients.

Adult

Occupational role and perceptions of substance misuse in Australia.

This study examined ways in which people from different occupational backgrounds in South Australia perceived issues relevant to the misuse of substances. Questionnaires were completed by representatives from eight occupational groups, namely, Doctors, Nurses, Ambulance Officers, Social Workers, Youth Workers, Teachers, the Police, and Probation and Parole Officers (in total, N = 276). Significant differences were found between occupational groups in their judgments of the relative incidence of substance misuse in the community, the comparative harmfulness of alcohol and marijuana, the attribution of alcohol misuse to personal inadequacy, and the efficacy of treatment of alcohol misuse.

Attitude to Health

A reproducible porcine vertebral fracture for biomechanical testing of spinal fixation devices.

To evaluate vertebral fracture fixation devices in the laboratory, it is necessary to produce identical and unstable fractures either in anatomic specimen or animal models. Consistent achievement of this goal has not been reported in the literature. This report presents a technique for the study of reproducibility for a particular vertebral fracture model. A precise anterior defect was created in a vertebra of each specimen drawn from a homogeneous population of mature sow spines. The spines were loaded to failure. Fracture reproducibility was shown by measurement of load and displacement, and confirmed by roentgenographic evaluation. The technique is easily applied to human specimens. Because there is a plethora of fracture fixation devices based on hooks, wires, or, more recently, plates and pedicle screws, the reliability of comparative testing of these devices in the laboratory requires an appropriate and reproducible fracture.

Animals

The diagnosis of intra-abdominal abscesses in patients with severe Crohn's disease.

A series of 24 patients with severe relapses of Crohn's disease responding poorly to conventional treatment with corticosteroids was studied to determine the incidence of intra-abdominal abscesses and the best means to detect them. Ultrasound scans proved to be difficult to interpret and unreliable. Computed tomography demonstrated abnormal bowel thickening in most cases, and showed seven of the eight intraabdominal abscesses. 111In leucocyte scintigraphy always demonstrated inflamed areas of bowel, but underestimated the extent of disease in three patients and overestimated it in five. All eight abdominal abscesses were detected, and there were no false-positive results. It was always possible to distinguish the abscess from inflamed bowel wall. Intra-abdominal abscess is not uncommon in patients with severe relapses of Crohn's disease which are not responsive to corticosteroid therapy, being present in about one-third of patients. 111In leucocyte scintigraphy is a simple and helpful test for differentiating between active inflammatory bowel disease and complicating abscesses, contributing significantly to the management of patients with severe Crohn's disease.

Abscess

Home detoxification from alcohol: its safety and efficacy in comparison with inpatient care.

The safety and short-term effectiveness of home detoxification (HD) was investigated by contrasting rates of treatment completion and of complications of 41 service users with those of a retrospectively matched inpatient comparison group. The latter comprised patients of a detoxification unit matched for age, sex and degree of alcohol dependence with HD subjects. HD subjects had severe problems with alcohol--they averaged 28.7 on the SADQ, 4.6 serious alcohol-related problems in the previous 2 months, a GGT of 123.8 and 174.6 reported units of alcohol consumed in the week before treatment. A high follow-up rate was achieved for both HD subjects and their relatives; there was close agreement between clients' reports, carers' reports and breathalyser readings with regard to further alcohol consumption. The HD subjects were visited at home an average of 6.9 times over 6.15 days. Chlormethiazole was prescribed in 36 cases at an average maximum daily dose of 6.3 capsules--significantly fewer than for the inpatient group. Both rates of completion and complication were virtually identical in the 2 groups. It is concluded that these data suggest HD is equivalent in both its safety and immediate efficacy to more expensive inpatient care.

Adult

Congestive heart failure and converting enzyme inhibition: failure of current prognostic criteria for predicting subsequent renal insufficiency.

Angiotensin-1-converting enzyme inhibitors have an effective and established role in the treatment of patients with congestive heart failure. However, a small number of such patients will subsequently develop renal insufficiency. These patients may be identified prior to, or shortly after, commencement of therapy by recognized criteria. This report describes 4 patients with congestive heart failure who developed severe renal insufficiency secondary to either enalapril or captopril therapy in the absence of any currently recognized predisposing factors. One patient died.

Aged