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Biomedical subjects

M Kelly

Publications and source records attributed to M Kelly.

At least 325 records · Page 18Linked to original sources

Glucose tolerance and the insulin response in recently drinking alcoholic patients: possible effects of withdrawal.

To investigate possible effects of withdrawal on carbohydrate metabolism in chronic alcoholic patients, intravenous glucose tolerance tests were performed in three periods in 11 alcoholic patients: early abstinence (less than three days), early abstinence plus ethanol (1 g/kg/BW IV), and late abstinence (three weeks later). According to liver biopsy results and laboratory tests, patients were classified as a group with liver damage (four cases) and a group without it (seven cases). In the group without damage, glucose tolerance expressed as K% and compared to a control group, was significantly decreased in early and late abstinence but not after the infusion of ethanol. Cases with damage also had glucose intolerance at admission. Plasma insulin levels after the glucose load were significantly lower at ten and 30 minutes in the group without damage, in early or late abstinence. They were normal in the presence of ethanol. Patients with liver damage presented higher basal and postglucose plasma insulin concentrations. It was concluded that glucose intolerance in alcoholic patients is a common finding that occurs in the presence or absence of liver damage. In cases with liver damage it seems to be due to peripheral insulin resistance. In those without damage it is related to low peripherovenous insulin levels.

Acute-Phase Proteins↗

Transient hypogonadotrophic hypogonadism after head trauma: effects on steroid precursors and correlation with sympathetic nervous system activity.

Transient hypogonadotrophic hypogonadism commonly occurs after major medical insults. Because data on testosterone precursors are sparse and because little is known about the aetiology of these changes, we studied the interactions of traumatic brain injury with gonadal steroidogenesis and with sympathetic nervous system activation. Patients were divided into two groups based upon the severity of neurological dysfunction using the Glasgow Coma Score (GCS); Group 1 less than 8, Group 2 greater than or equal to 8. Group 1 was further divided into those patients treated (Group 1b) and those not treated with dexamethasone (Group 1a). Plasma levels of testosterone, androstenedione, 17-hydroxyprogesterone, DHEA sulphate, cortisol, LH, FSH, and the catecholamines noradrenaline (NE), adrenaline (EPI) and dopamine were measured in 31 acutely brain injured men, aged 18-95, shortly after their accident and 4 days later. In all patients, NE and EPI were elevated on admission (NE: 841 +/- 105 (SEM) pg/ml; EPI: 191 +/- 32 pg/ml and there were highly significant inverse correlations between admission NE (r = -0.52, P less than 0.003) and EPI (r = 0.44, P less than 0.02) levels and day 4 testosterone concentrations. Testosterone fell 53% (P less than 0.001) in 13 Group 1a men, but only 25% (P = NS) in the less severely injured. Similar reductions occurred in cortisol and the steroid precursors. However, only testosterone, 17-hydroxyprogesterone, and DHEA sulphate levels were significantly lower than normal on day 4. LH and FSH levels were also significantly reduced from elevated admission levels. In the eight men treated with dexamethasone (8-40 mg/ml) (Group 1b), the decrease in testosterone, LH and FSH concentrations were similar to those present in Group 1a. Thus, severe traumatic brain injury leads to hypogonadotrophic hypogonadism which affects testosterone and its precursors. The magnitude of the hormonal dysfunction is dependent upon the severity of the neurological insult. Finally, the decrease in testosterone is significantly correlated with admission catecholamine levels, which may suggest a role for the sympathetic nervous system (SNS) in mediating this response in men.

Adolescent↗

Retinoic acid-induced differentiation of human neuroblastoma: a cell variant system showing two distinct responses.

Retinoic acid (RA) has been shown to induce the differentiation of human neuroblastoma cells in vitro. In this study, we describe two variants of the SK-N-SH human neuroblastoma cell line that have dramatically different responses to RA. RA induces neuronal-like differentiation characterized by extensive neurite outgrowth, thick neurite bundles, and large cellular aggregates of SK-N-SH-N (SH-N) cells. In contrast, RA treatment of SK-N-SH-F (SH-F) cultures transforms the small neuroblast cells into large flattened, fibroblastic or epithelial-like cells. Karyotype analysis verified that the SH-N and SH-F cultures were derived from a common precursor cell. Confirmation of their markedly different responses to RA was obtained by metabolic labelling of glycoproteins and SDS-PAGE analysis. While both sublines showed very similar Coomassie-labelled protein bands and glycoprotein profiles in control cultures, dramatic differences between the lines were revealed following RA treatment. In contrast to their similar protein profiles, untreated SH-N and SH-F cells had quite different patterns of ganglioside biosynthesis in that GM3 was detected in SH-F cells but not in SH-N, while GM1 was only detected in SH-N. Cellular RA binding protein (CRABP) was detected in both SH-F and SH-N cells and their RA-transformed derivatives. These results demonstrate heterogeneity in the response to RA of neuroblastoma cells derived from a common origin that cannot be accounted for by differences in CRABP content. The SH-N and SH-F neuroblastoma sublines should provide a useful system for further studies of the molecular processes through which RA exerts its differentiation-inducing activity on this type of tumor.

Carrier Proteins↗

Fibrous dysplasia of the paranasal sinuses.

Fibrous dysplasia (FD) of the paranasal sinuses is rare and often presents a diagnostic challenge. It is usually secondary to extension of disease from adjacent bones and is rarely limited to the sinuses. We have described three cases of FD involving the paranasal sinuses, including the first reported case of FD isolated to the sphenoid sinus. A brief update of the clinical aspects, radiographic appearance, diagnosis, and management of craniofacial FD is provided.

Adolescent↗

Infarcts of the inferior division of the right middle cerebral artery: mirror image of Wernicke's aphasia.

We searched the Stroke Data Bank and personal files to find patients with CT-documented infarcts in the territory of the inferior division of the right middle cerebral artery. The most common findings among the 10 patients were left hemianopia, left visual neglect, and constructional apraxia (4 of 5 tested). Five patients had an agitated confusional state that was characterized by hyperactivity, restlessness, and easy distractibility. Motor and sensory abnormalities were not severe or persistent. The most common cause was cardiogenic embolism.

Aged↗

The kinetic response of haemopoietic precursor cells, in vivo, to highly purified, recombinant interleukin-3.

Interleukin-3 is a murine haemopoietic cell growth factor which has now been prepared in recombinant form, rIL-3. This purified material has been shown to act, in vitro, in a comparable manner to the native material and has recently been shown to have an in vivo effect on the committed, in vitro colony-forming cells. We have examined the effects, in vivo, of low acute and chronic infusion doses on the pluripotent haemopoietic spleen colony-forming cells, CFU-S, (stem cells). The proliferation rate of CFU-S is rapidly increased after administration of rIL-3. This is followed by a migration of the more mature CFU-S to the spleen where, particularly under chronic rIL-3 treatment there is a large increase in CFU-S numbers. The increased proliferation of CFU-S is accompanied by increased differentiation in the form of a large increase in in vitro IL-3 responsive cells. The changes observed were not the result of endotoxin contamination in the rIL-3 preparation. Significantly, however, larger doses of lipopolysaccharide, did mimic the effects of rIL-3 in vivo. IL-3 was not detected in the blood following LPs treatment but it is suggested that LPS acts indirectly on haemopoietic precursor cells by eliciting local production of IL-3, perhaps from adjacent T cells or stromal cells.

Animals↗

The total condylar prosthesis.

Forty knees with total condylar prostheses have been followed for ten years or more. There were five failures, one due to infection and four directly related to either improper selection or technical reasons. Thirty-five knees (87.5%) have a satisfactorily functioning arthroplasty after ten years. There were no loose components and no complete radiolucent lines. Technique and correct alignment are most important and, provided that the operation is correctly performed, conventional polymethyl methacrylate cement fixation is completely adequate. The absence of progressive adverse radiologic changes suggests that knee arthroplasties have a considerable life expectancy.

Aged↗

Pharmacist involvement in the Concord Hospital clinical review programme.

Drug audits have continued at Concord Hospital and the Pharmacy Department now contributes to the Clinical Review Programme on a frequent basis. Drug audits are descriptive observational studies which provide information as a tool for discussion, and the opportunity to review prescribing habits. From this very simple beginning the pharmacy has progressed to a series of more complex criteria based audits.

Adult↗

The response of several murine embryonal carcinoma cell lines to stimulation of differentiation by alpha-difluoromethylornithine.

In an attempt to better establish the relationship between polyamine levels and the differentiation of embryonal carcinoma cells, we have examined the ability of alpha-difluoromethylornithine (DFMO), a known inducer of differentiation in one embryonal carcinoma cell line, to stimulate the differentiation of embryonal carcinoma cells from a variety of cell lines. Differentiation was monitored using a variety of criteria including morphological alterations and changes in biochemical and antigenic parameters. Depending on their response to difluoromethylornithine, three classes of cell lines could be identified, those which 1) differentiate extensively, 2) differentiate poorly, and 3) fail to differentiate. Three different classes of embryonal carcinoma cell lines reflect differential changes in polyamine levels resulting from inhibition of ornithine decarboxylase enzyme activity by DFMO. The specific cell lines which exhibit large decreases in both ornithine decarboxylase activity and polyamine levels also show extensive differentiation. The cell lines which show only moderate decreases in enzyme activity and polyamines differentiate poorly while the cell lines which fail to respond to DFMO in that polyamines do not drop below the threshold level necessary to induce differentiation fail to differentiate. These studies suggest that decreases in intracellular polyamines induce EC cell differentiation in vitro.

Animals↗

Alterations in polyamine metabolism during embryonal carcinoma cell differentiation in vitro.

Murine embryonal carcinoma (EC) cells can be stimulated to differentiate by several chemical inducers. Since the response of EC cells to induction is likely to occur shortly after exposure to the inducer, we report here the changes that occur in polyamine levels in a number of EC cell lines shortly after exposure to two chemical stimuli, alpha-difluoromethylornithine (DFMO) and retinoic acid (RA). Our results suggest that polyamine levels are important in determining the state of EC cell differentiation, but that reduction in these levels alone is not sufficient to induce differentiation in all the EC cell lines tested. Also, it is apparent that RA does influence levels of polyamines. However, this influence does not seem to be mediated through direct interaction with ODCase.

Animals↗

Transient hypogonadotropic hypogonadism caused by critical illness.

The effects of acute severe illness on pituitary-gonadal function were determined in 35 men and 19 women, including 12 who were postmenopausal. Seventeen men and 5 women had traumatic brain injury which resulted in coma. Twelve postmenopausal and 2 premenopausal women had intracranial vascular accidents. Eleven men had myocardial infarctions, while 7 men underwent elective surgery. Serial plasma samples were examined for testosterone (men), percentage of ultrafiltrable testosterone (men), estradiol (women), sex hormone-binding globulin, LH, and FSH. In men, mean testosterone levels fell by 271 +/- 72 (+/- SE), 202 +/- 63 and 195 +/- 75 ng/dl within 24 h of brain injury, myocardial infarction, or elective surgery, representing decreases of 55%, 43%, and 58%. Further declines occurred in the first and third groups to mean nadirs of 93 +/- 16 and 117 +/- 5 ng/dl, respectively. During recovery of neurological function there was no correlation between the testosterone level and the degree of neurological impairment; testosterone levels eventually returned to normal (627 +/- 77 ng/ml). The percentage of ultrafiltrable testosterone and sex hormone-binding globulin did not change in any group. Although significant decreases in mean immunoreactive LH and FSH levels were found after head trauma, and decreases in FSH were found in the men after surgery, these changes occurred after the decline in testosterone. Despite the fall in basal gonadotropin levels in the head trauma group, there were no significant differences in the gonadotropin responses to GnRH (100 micrograms) in 4 patients during their acute illness or recovery. LH, FSH, and estradiol levels in the premenopausal women were significantly lower on the second day of brain injury (LH, 10.3 +/- 4.7 vs. 3.5 +/- 0.6 mIU/ml; FSH, 3.8 +/- 1.9 vs. 1.4 +/- 0.8 mIU/ml, estradiol, 200 +/- 41 vs. 102 +/- 16 pg/ml) and remained suppressed for 7 days. Gonadotropin levels also fell in the postmenopausal women within 24 h; reductions in LH of 74% and in FSH of 62% were present by day 7 of study. We conclude that both men and women who are critically ill uniformly develop temporary hypogonadotropic gonadal insufficiency regardless of their illness. In men, it is manifested by low testosterone levels, while a comparable decrease in estradiol is present in women. The low testosterone concentrations are not due to reduced sex hormone-binding capacity. Based upon our data in postmenopausal women, hypogonadotropism also occurs in the presence of nonfunctioning gonads. Although our studies do not completely establish the pathophysiology of this disorder, they suggest a suprapituitary origin.

Adolescent↗

Is percutaneous coronary angioplasty less expensive than bypass surgery?

Percutaneous transluminal coronary angioplasty is widely considered to be an acceptable and less expensive alternative to bypass surgery in carefully selected patients. We compared expenditures related to cardiac care for 79 unselected patients undergoing coronary angioplasty with expenditures for 89 unselected patients undergoing elective coronary bypass surgery without a previous attempt at angioplasty. All the patients had single-vessel disease. The mean aggregate one-year monetary outlay was 15 per cent lower in the angioplasty group than in the bypass-surgery group. A major component of the expense of angioplasty was the treatment of restenosis in the 33 per cent of patients in this group in whom this late complication occurred. We conclude that percutaneous transluminal coronary angioplasty has potential for reducing expenditures for cardiac revascularization and that a further reduction may be obtainable when the rates of restenosis are improved.

Angioplasty, Balloon↗

Abused, neglected, and nonmaltreated children's conceptions of moral and social-conventional transgressions.

The effect of child maltreatment on children's social-cognitive development was examined by investigating abused, neglected, and nonmaltreated children's judgments regarding the permissibility of social-conventional and moral transgressions pertaining to physical harm, psychological distress, and the unfair distribution of resources. Abused and neglected children and a control group of nonmaltreated children matched on IQ, age, and social class judged the seriousness, deserved punishment, generalizability, and rule contingency of familiar transgressions for themselves and others. Abused subjects were more likely than neglected subjects to consider psychological distress to be universally wrong for others; neglected subjects were more likely than abused subjects to judge the unfair distribution of resources to be universally wrong for themselves. Abused and control children, but not neglected children, judged all transgressions to deserve more punishment when committed by others than when committed by the self. All children distinguished between morality and social convention and between different types of moral transgressions on all 4 criteria. Furthermore, all children were more egocentric in their judgments for the self than for others. These findings are discussed in relation to research on the effects of child maltreatment and on moral judgment.

Child↗