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Biomedical subjects

M Kelly

Publications and source records attributed to M Kelly.

At least 19 recordsLinked to original sources
PubMed1992

Effect of using protocols on medical care: randomised trial of three methods of taking an antenatal history.

OBJECTIVE: To compare the effectiveness of three methods of taking an antenatal history on the quality of obstetric care. DESIGN: Randomised controlled trial. SETTING: Antenatal clinic of St James's University Hospital, Leeds. SUBJECTS: 2424 women attending the hospital for the first (booking) visit. INTERVENTIONS: Histories were taken by midwives using an unstructured paper questionnaire, a structured paper questionnaire (incorporating a checklist), or an interactive computerised questionnaire (incorporating 101 clinical reminders). MAIN OUTCOME MEASURES: The number of clinical responses to factors arising from the antenatal booking history according to method of taking the history. Actions were categorised as medical and surgical, obstetric, personal, current symptoms and treatment, related to maternal age, and related to two common actions (cervical smear testing and dental hygiene) and were weighted for clinical importance by 10 obstetricians. RESULTS: Overall the unstructured questionnaire generated 1063 actions, the structured questionnaire 1146, and the computerised questionnaire 1122. The clinical importance of these actions was lowest for the unstructured questionnaire (overall total value score 1987 v 2182 and 2110 for the structured and computerised questionnaires respectively). The structured questionnaire was better than the computerised questionnaire in the medical and surgical (total value score 191 v 184), obstetric (275 v 241), and personal (430 v 360) categories but inferior in the current symptoms category (179 v 191). CONCLUSION: Structured questionnaires (computerised or paper) provide more and better information, and their use improves clinical response to risk factors. Computerised systems offer no further advantage in antenatal clinics.

Clinical Protocols↗
PubMed1992

GenBank.

The GenBank nucleotide sequence database now contains sequence data and associated annotation corresponding to 85,000,000 nucleotides in 67,000 entries from a total of 3,000 organisms. The input stream of data coming into the database is primarily as direct submissions from the scientific community on electronic media, with little or no data being keyboarded from the printed page by the databank staff. The data are maintained in a relational database management system and are made available in flatfile form through on-line access, and through various network and off-line computer-readable media. The data are also distributed in relational form through satellite copies at a number of institutions in the U.S. and elsewhere. In addition, GenBank provides the U.S. distribution center for the BIOSCI electronic bulletin board service.

Animals↗
PubMed1992

Motor neurone disease: a hospice perspective.

OBJECTIVE: To describe and evaluate the management of patients with motor neurone disease from the perspective of a hospice. DESIGN: Retrospective analysis of hospice medical and nursing notes. SETTING: Established 62 bed teaching and research hospice. SUBJECTS: 124 patients with motor neurone disease cared for by the hospice between January 1980 and November 1990. MAIN OUTCOME MEASURES: Patient profile; functional status; symptom control and use of opioids; insight; mode and management of death. RESULTS: 124 patients (67 women, 57 men) had a mean age 63.9 years. The median length of admission was 61.5 days (range 1 to 2147). 84 patients (68%) were aware of their diagnosis and its implications when first seen by a hospice doctor. Functionally, the patients were very dependent. Symptoms such as pain, dyspnoea, and insomnia were major problems that responded well to opioids. Many patients were noted to deteriorate "suddenly," and in 58% of cases death occurred within 24 hours of this deterioration. When dying, 106 patients (94%) were peaceful and settled. 101 patients (89%) received opioids during this dying period. No patient chocked to death. CONCLUSIONS: Although motor neurone disease is an uncommon disorder, many of its symptoms occur commonly in medical practice and must be actively treated. Opioids are both safe and effective for such treatment. The term chocking is both inaccurate and inappropriate in describing the cause of death in motor neurone disease and its use should be abandoned.

Adult↗
PubMed1992

Leg extensor power and functional performance in very old men and women.

1. Residents of a chronic care hospital (13 men of mean age 88.5 +/- 6 SD years and 13 women of mean age 86.5 +/- 6 SD years) who had multiple pathologies were assessed for leg extensor capability in several ways. 2. A custom-built rig was used to assess leg extensor power, that is, maximal power output over less than 1 s in a single extension of one leg. Performance measures were obtained by timing chair rises (from a standard chair 0.43 m high), stair climbing (four risers, total height 0.635 m) and a walk (6.1 m). For each measurement the best of several trials were recorded as definitive. 3. Leg extensor power was significantly correlated with all performance measures, but the performance measures were not related to each other except for chair rising and walking speed. 4. Women had significantly less extensor power than men, but their power explained more of the variance in performance, e.g. power accounted for 86% of the variance in walking speed. 5. There was no relation within the group between age and any of the variables measured. 6. Measurement of leg extensor power in frail elderly people may prove useful in focusing effective rehabilitation programmes.

Aged↗
PubMed1992

A longitudinal analysis of adherence and health status in childhood diabetes.

Applied structural equation modeling to a longitudinal data set of 193 youngsters with insulin-dependent diabetes mellitus assessed on two occasions, an average of 1.65 years apart. Six adherence constructs, Injection, Exercise, Diet Type, Testing-Eating Frequency, Calories Consumed, and Concentrated Sweets, were quantified from 24-hr recall interviews conducted with mother and child. Glycemic control was indexed by glycosylated hemoglobin (HA1C); lipid metabolism was indexed by fasting triglyceride levels (TRIG). The relationship of each adherence construct to metabolic control was tested separately. Patient age and disease duration served as exogenous variables in all models. Testing-Eating Frequency was associated with HA1C and Injection was associated with TRIG; in both cases better adherence was associated with better metabolic control. However, the standardized regression weights and variance accounted for were small. Patient age was a predictor of both adherence and metabolic control; older youngsters were less adherent and were in worse metabolic control. Inspection of models for younger versus older children suggested that age-homogeneous models improved prediction, but adherence and metabolic control linkages remained weak. Suggestions for refining the model are provided.

Blood Glucose↗
PubMed1992

Angiotensin II increases proto-oncogene expression and phosphoinositide turnover in vascular smooth muscle cells via the angiotensin II AT1 receptor.

OBJECTIVES: The aim of this study was to determine which angiotensin II receptor (AT receptor) mediates proto-oncogene expression and phosphoinositide metabolism in vascular smooth muscle cells in vitro. DESIGN: The AT receptor antagonists DuP753 (losartan), an AT1 antagonist, and PD 123319, an AT2 antagonist, were used to characterize AT receptors on cultured vascular smooth muscle cells derived from the rat mesenteric artery and to identify which receptor subtype mediates the angiotensin II-induced increase in proto-oncogene expression and phosphoinositide metabolism. METHODS: Rat mesenteric artery vascular smooth muscle cells were grown using standard cell culture methods. Proto-oncogene induction was measured using Northern blotting. Phosphoinositide breakdown was assessed by measuring [3H]-inositol phosphates released from prelabelled cells. RESULTS: Receptor-binding studies revealed that the AT1 receptor predominated on vascular smooth muscle cells. Incubation of quiescent cells with 0.1 mumol/l angiotensin II resulted in a 65% increase in total [3H]-inositol phosphates released compared with unstimulated cells and in a rapid accumulation of c-fos messenger RNA (mRNA). Pre-incubation of the cells with 10(-5) mol/l PD 123319 had no effect on either total inositol phosphates release or c-fos mRNA induction. Both responses, however, were totally abolished by pre-incubation of the cells with 10(-5) mol/l losartan or saralasin. CONCLUSIONS: Angiotensin II acts through the AT1 receptor to increase c-fos expression and phosphoinositide turnover in vascular smooth muscle cells. These mechanisms may be important in angiotensin II-induced smooth muscle hypertrophy.

Angiotensin II↗
PubMed1992

[Controlled study of the effect of silymarin on alcoholic liver disease].

A controlled trial on the use of Silymarin in patients with alcoholic liver disease was performed. Seventy two patients were admitted to the trial and randomly assigned to an experimental or controls group. Experimentals received 280 mg/day of Silymarin and controls an equal number of placebo tablets. Three patients on placebo and nine on Silymarin were lost from control (p = 0.035), remaining in control 34 patients receiving placebo and 25 patients receiving the drug. Both groups did not differ in their initial laboratory assessment and were followed up for an average of 15 months. Ten patients died during the follow up (5 in placebo and 5 in Silymarin); life table analysis did not show significant differences in mortality. Patients who died had lower serum albumin and prothrombin time and higher total bilirubin, alkaline phosphatases and CCLI on the initial clinical and laboratory assessment. Final laboratory values and their changes in those who survived did not differ between Silymarin and placebo. Twenty two patients on placebo (65%) and 14 on Silymarin (58%) recognized alcohol ingestion or had a positive urine sample analysis for alcohol during follow up. Those who abstained from alcohol had a significant fall in gamma glutamyl transferase during follow up. No other significant differences were observed between these two groups. It is concluded that in this trial, Silymarin did not change the evolution or mortality of alcoholic liver disease.

Double-Blind Method↗
PubMed1992

Effects of alcohol on E2 beta-stimulated luteinizing hormone in ovariectomized rhesus monkeys.

Anovulation is a frequent concomitant of alcohol abuse, but it has been difficult to assess the acute effects of alcohol on ovulation. Estradiol benzoate (E2 beta) can stimulate a luteinizing hormone (LH) surge in ovariectomized monkeys that appears to be associated with increased luteinizing hormone-releasing hormone (LHRH) pulse frequency and amplitude. The acute effects of alcohol (2.5 and 3.5 g/kg) and an isocaloric sucrose control solution on LH and follicle-stimulating hormone (FSH) secretory activity were studied in five ovariectomized monkeys 41 to 51 hours after administration of E2 beta (42 micrograms/kg, IM). Integrated plasma samples were collected at 20-minute intervals over 10 hours. Under sucrose control conditions, LH increased to 445 and 584 ng/ml within 46 to 49.3 hours after E2 beta administration in two monkeys and high-amplitude LH pulses were evident in three monkeys. Alcohol (2.5 and 3.5 g/kg) significantly decreased the number of LH peaks and valleys (p < 0.01). Peak blood alcohol levels averaged 195 and 291 mg/dl. After 2.5 g/kg alcohol, there was no LH surge or LH pulses in four of five monkeys. A delayed LH surge occurred in one monkey 48 to 50.6 hours after E2 beta when blood alcohol levels decreased to 62 mg/dl. After 3.5 g/kg alcohol, no monkey had an LH surge and pulsatile LH release was significantly reduced in comparison to control conditions (p < 0.01). FSH levels remained stable across alcohol and control conditions. These data suggest that alcohol attenuates pituitary release of LH in response to E2 beta stimulation. These findings are consistent with menstrual cycle disruptions observed in alcohol-dependent women, social drinkers, and in a primate model of alcoholism.

Animals↗
PubMed1991

Bombinin-like peptides with antimicrobial activity from skin secretions of the Asian toad, Bombina orientalis.

The structures and hemolytic and bactericidal activities of three bombinin-like peptides, or BLP-1-3, from the skin of Bombina orientalis are described. The peptides were isolated from the skin of B. orientalis and sequenced by tandem mass spectrometry and are amphipathic, cationic peptides of 25-27 amino acids in length. The sequence of the most abundant member (BLP-1) is: Gly-Ile-Gly-Ala-Ser-Ile-Leu-Ser-Ala-Gly-Lys-Ser-Ala-Leu-Lys-Gly-Leu- Ala-Lys-Gly-Leu-Ala-Glu-His-Phe-Ala-Asn-NH2. All three peptides were found to share considerable, but not complete, homology with bombinin, an antimicrobial, hemolytic peptide first isolated by Michl and Csordas (Csordas, A., and Michl, A. (1970) Monatsh. Chem. 101, 182-189) from the skin of Bombina variegata. The BLPs have been assayed for antibiotic and hemolytic activity and found to be more potent than magainin 2 (a related antimicrobial peptide from Xenopus laevis) in their ability to kill bacteria. However, no significant hemolytic activity was found for these peptides which suggests a selectivity for prokaryotic over eukaryotic membranes. The molecular basis for antibacterial activity is presumed to be due to their predicted amphipathic alpha-helical structures which is supported by circular dichroism measurements that found significant helical content (63-69% alpha-helix) in 40% trifluoroethanol. Last, a cDNA library was constructed from the skin of B. orientalis and screened with an oligonucleotide probe complementary to the COOH terminus of BLP-1. Several clones were isolated and sequenced that encode BLP-1 and BLP-3, as well as an additional peptide (BLP-4) that differs by two amino acid substitutions from BLP-3.

Amino Acid Sequence↗
PubMed1991

GenBank.

The GenBank nucleotide sequence database now contains sequence data and associated annotation corresponding to 56,000,000 nucleotides in 45,000 entries. The input stream of data coming into the database has largely been shifted to direct submissions from the scientific community on electronic media. The data have been installed in a relational database management system and are made available in this form through on-line access, and through various network and off-line computer-readable media. In addition, GenBank provides the U.S. distribution center for the BIOSCI electronic bulletin board service.

Base Sequence↗
PubMed1991

Latissimus dorsi musculocutaneous flap for elbow extension.

The latissimus dorsi mycocutaneous flap has developed a reputation for its versatility in both skin and soft tissue coverage and for restoration of elbow function in both flexion and extension. In a case presented, a large extra-abdominal desmoid was removed along with the entire deltoid and three-quarters of the triceps. The latissimus dorsi was elevated with a large overlying skin island and rotated on its neurovascular pedicle into the defect in the posterior shoulder and upper arm to replace the resected triceps and deltoid muscle, and to provide coverage in this region.

Back↗
PubMed1991

Direct determination of homovanillic acid release from the human brain, an indicator of central dopaminergic activity.

The plasma concentration of the dopamine (DA) metabolite, homovanillic acid (HVA), is used as an indicator of central nervous system dopaminergic activity. Using percutaneously inserted catheters we were able to obtain blood samples simultaneously from the right and left internal jugular veins. Veno-arterial HVA plasma concentration differences combined with adjusted organ plasma flows were used, according to the Fick Principle, to determine the HVA overflow from the brain. The HVA overflow from the liver was also measured. HVA overflow from the brain represented 12% of the total body HVA production. A similar amount was released from the liver, illustrating the limited validity of peripheral plasma HVA measurements as an indicator of central dopaminergic activity. HVA release from the human brain displayed a degree of asymmetry, the overflow into the left internal jugular vein being 36% greater than that into the right. Cerebral venous blood flow scans indicated that cortical cerebral regions drained preferentially into the right internal jugular; by inference the higher HVA overflow on the left originated from dopamine-rich subcortical brain areas. Since HVA in plasma may arise from the metabolism of DA existing either as a neurotransmitter or a norepinephrine (NE) precursor we measured the internal jugular vein plasma concentrations of NE, and its metabolite dihydroxyphenylglycol (DHPG), to determine whether they displayed a similar pattern of release to HVA. The overflow of both NE and DHPG into the right internal jugular vein was approximately double that on the left. Since the overflow of HVA did not parallel that of NE and DHPG it may be inferred that the origin of much of the subcortically produced HVA is from dopaminergic neurons and not from the metabolism of precursor DA in noradrenergic neurones or cerebrovascular sympathetic nerves.

Adolescent↗
PubMed1991

Effects of intoxication on the catecholamine response to multisystem injury.

In patients suffering isolated head trauma, we have previously shown that levels of circulating catecholamines obtained within 48 hours of trauma correlate with the severity of brain injury and predict outcome and that intoxication blunts this response. The effects of alcohol on the increase in catecholamines in systematically injured patients, however, have not been well defined. From 1983 to 1990, 78 patients (74% male; median age 30 years) with blunt head and multisystem injury, who also had alcohol levels measured within 5 hours of injury, were studied. Norepinephrine and epinephrine levels were assayed by a radioenzymatic technique. Injury severity was assessed by the admission Glasgow Coma Scale (GCS) score (4-15; median, 12), the Injury Severity Score (ISS) (13-50; median, 25) and the volume of blood products administered within the first 24 hours (0-14.4 L; median, 0.5 L). The impact of alcohol on the norepinephrine response to injury was analyzed using multiple linear regression models, including polynomial interaction terms. Norepinephrine levels significantly (p less than 0.0001) correlated with the GCS score and ISS. However, alcohol significantly lowered the norepinephrine response to decreasing GCS score (R = 0.49, p less than 0.002) and to increasing ISS (R = 0.51, p less than 0.0006). The blunting of the catecholamine response was most marked in those severely injured. The rise in norepinephrine concentrations seen with increasing volume of blood replacement was not affected by intoxication. An association between injury severity and epinephrine levels was also present, but not as consistently. Epinephrine concentrations rose with falling GCS score and with increasing ISS values, but unlike norepinephrine, there were no apparent effects of alcohol on changes in epinephrine levels. Thus, in patients suffering head and multisystem injury, catecholamine changes reflect the severity of injury using three different scalers. Furthermore, intoxication blunts only the norepinephrine component of this important biologic response.

Adolescent↗
PubMed1991

Double blind, placebo controlled trial of metronidazole in Crohn's disease.

A double blind study compared the efficacy of metronidazole in two doses (20 mg/kg, 10 mg/kg) with placebo in patients with Crohn's disease. One hundred and five patients participated but only 56 completed the 16 week study -21 were withdrawn for deterioration of symptoms, 17 for adverse experiences, and 11 for protocol violation. Significant improvement in disease activity as measured by the Crohn's disease activity index (metronidazole 20 mg/kg, 97 units; metronidazole 10 mg/kg, 67 units; placebo -1 unit, p = 0.002) and serum orosomucoid (metronidazole 20 mg/kg/day, 49; 10 mg/kg/day, 38; placebo, -9, p = 0.001)) were detected. Changes in C reactive protein concentrations did not achieve significance when all three groups were considered but were significant when all metronidazole treated patients were grouped and compared with the placebo treated patients (0.8 v -0.9, p less than 0.05). Although patients receiving metronidazole 20 mg/kg/day had a greater improvement in disease activity than those receiving 10 mg/kg/day (difference 30 units (95% confidence intervals -27-87), the small sample size may have precluded the detection of statistical significance. Preliminary analysis suggests that metronidazole was more effective in patients with disease confined to the large intestine or affecting both small and large bowel than in those with small bowel disease only. There were no differences in remission rates between metronidazole and placebo treated patients. We conclude that metronidazole warrants further assessment in the treatment of patients with active Crohn's disease.

Analysis of Variance↗