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Biomedical subjects

A Long

Publications and source records attributed to A Long.

At least 127 records · Page 7Linked to original sources

Oral treatment for constitutional delay of growth and puberty in boys: a randomised trial of an anabolic steroid or testosterone undecanoate.

Thirty three boys (mean 14.6 years old, range 12.8-16.2 years) with constitutional delay of growth and puberty were randomised into two groups to determine which form of oral treatment would give the better anthropometric response. The two drugs were administered by mouth (one tablet/day) for a mean of 3.5 months (range 3-7 months). At randomisation, 17 boys received testosterone undecanoate (40 mg/day) and 16 oxandrolone (2.5 mg/day). At the start of treatment they were prepubertal or in early puberty, their height SD score was -1.97 in boys treated with testosterone and -2.21 in those treated with oxandrolone, and their growth rates were 4.3 and 4.2 cm/year respectively. Both sex steroid and anabolic steroid treatments induced a significant growth acceleration in all patients except four (three treated with testosterone and one with oxandrolone). When treated with the alternative sex steroid, all four non-responders had a significant anthropometric response. In all boys the induced growth acceleration was sustained when treatment was interrupted. There was no significant difference in the induced growth spurt and bone maturation between the two groups. Spontaneous progress into puberty was achieved in all boys with an increase in testicular volume from a mean of 4.6 to 8.5 ml. The rate of development in secondary sexual characteristics was also similar in the two groups. These data suggest that oral testosterone and oxandrolone are equally effective in the treatment of growth delay in boys with constitutional delay of growth and puberty.

Administration, Oral↗

Performance and metabolic effects of benzodiazepine during submaximal exercise.

The present study examined whether benzodiazepine (BZ) intake alters performance and selected hormonal and metabolic variables during submaximal exercise. Seven triathletes completed two cycling trials at 85% maximum O2 uptake starting 3 h after an ingestion of either a placebo (PLA) of gelatin or BZ (1.5 mg lorazepam) and continuing until exhaustion, according to a double-blind randomized protocol. Blood samples were collected at rest; 5, 10, and 15 min; and exhaustion for dopamine (DA), norepinephrine (NE), epinephrine (Epi), adrenocorticotropic hormone (ACTH), cortisol (CORT), insulin (INS), free fatty acid, blood glucose, and lactate (La) determinations. Time of cycling was not significantly changed after BZ or PLA administration (22.9 +/- 2.5 vs. 23.5 +/- 3.8 min, respectively). A decrease in CORT and an increase in INS (P < 0.05) were observed with BZ before cycling. In comparison with rest, exercise resulted in a decrease in INS and an increase in all the other variables investigated (P < 0.001), but DA, NE, Epi, ACTH, CORT, La, and free fatty acid were significantly less elevated under BZ (P < 0.05). No change was found in glucose and INS levels between the two treatments at the end of the test. There was a strong correlation under both PLA and BZ conditions between DA, NE, Epi, and ACTH and also between Epi and La levels. From these data, BZ intake did appear to alter metabolism but did not influence performance during intense submaximal exercise.

Adrenocorticotropic Hormone↗

The AAQA/ACHS National QA database: a 12 month update. Australasian Association for Quality in Health Care. Australian Council on Healthcare Standards.

In its first 12 months of operation, the AAQA/ACHS National QA Database has succeeded in its aim of providing a networking channel for quality coordinators and managers. Thanks to the cooperation and interest of many health care professionals, the database now holds some 1800 entries and in its first year was accessed by more than 160 individuals. Contributors rated 86% of quality activities submitted as effective or very effective. The majority of entries were submitted by facilities with less than 150 beds and almost half of the entries came from NSW. Over half the entries were submitted by nursing and allied health professionals. The article describes the most common QA methods contributed to the database. Ongoing input to the database is essential. Individuals actively involved in quality activities are urged to contribute their experience, particularly in areas currently under-represented in the database.

Australia↗

Conventional protein kinase C isoforms are not essential for cellular proliferation of a T cell lymphoma line.

The role of conventional protein kinase C (PKC) isoforms in the proliferation of a T cell lymphoma line was investigated, PKC isozyme-deficient cell lines were generated from HuT 78 which expresses PKC isoforms alpha, beta, epsilon and zeta. The first of these, K-4, expresses PKC alpha, epsilon and zeta but not beta. L-2, a mutant of K-4, expresses PKC alpha and zeta but expresses neither PKC alpha, beta, gamma, epsilon nor zeta when cultured continuously in PMA (L-2/PMA). All four cell lines continued to proliferate although at reduced rates in the presence of the PKC inhibitors staurosporine and H-7. K-4 and HuT 78 undergo growth arrest when activated with PMA (rate of proliferation decreases by 76 and 95%, respectively). While PMA-induced growth arrest occurs in L-2 cells which possess PKC alpha and zeta, PMA-induced growth arrest does not occur in L-2/PMA which is deficient in these isoforms. As these cell lines continue to proliferate in the presence of PKC inhibitors and since proliferation occurs in the absence of PKC isoforms (L-2/PMA), the results suggest that neither conventional PKC nor the epsilon and zeta isoforms are essential for proliferation of these cells. These data further suggest that PKC alpha and/or zeta may be involved in PMA-induced growth arrest.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Selective serotonin reuptake inhibitors: meta-analysis of efficacy and acceptability.

OBJECTIVE: To examine the evidence for using selective serotonin reuptake inhibitors instead of tricyclic antidepressants in the first line treatment of depression. DESIGN: Meta-analysis of 63 randomised controlled trials comparing the efficacy and acceptability of selective serotonin reuptake inhibitors with those of tricyclic and related antidepressants. MAIN OUTCOME MEASURES: Improvement in mean scores on Hamilton depression rating scale for 53 randomised controlled trials. Pooled drop out rates from the 58 trials which reported drop out by treatment group. RESULTS: Among the 20 studies reporting standard deviation for the Hamilton score no difference was found in efficacy between serotonin reuptake inhibitors and tricyclic and related antidepressants (standardised mean difference 0.004, 95% confidence interval -0.096 to 0.105). The difference remained insignificant when the remaining 33 studies that used the 17 item and 21 item Hamilton score were included by ascribing weighted standard deviations. The odds ratio for drop out rate in patients receiving serotonin reuptake inhibitors compared with those receiving tricyclic antidepressants was 0.95 (0.86 to 1.07). Similar proportions in both groups cited lack of efficacy as the reason for dropping out but slightly more patients in the tricyclic group cited side effects (18.8% v 15.4% in serotonin reuptake group). CONCLUSIONS: Routine use of selective serotonin reuptake inhibitors as the first line treatment of depressive illness may greatly increase cost with only questionable benefit.

Antidepressive Agents, Tricyclic↗

The role of the nurse providing therapeutic care for the suicidal patient.

In this study, nurses perceived that the implementation of special supervision is the most effective preventive method in the nursing care of suicidal patients, but they also expressed the view that special supervision is non-therapeutic. The results of these findings show that it is possible to provide nursing care in the prevention of further harm to the patient but that nurses may not necessarily be proficient in demonstrating the interpersonal caring skills essential for the development of a therapeutic relationship and hence patient recovery. This paper demonstrates there is now: (a) a need for special supervision as a preventive method when caring for the suicidal patient; (b) a need for a planned therapeutic programme of care during special supervision; (c) a need for the development of essential interpersonal and counselling skills and dimensions for effective therapeutic intervention and empathic nursing care; (d) a need to bridge the gulf between theory and practice by giving nurses the opportunity to practise those skills in the clinical setting under the supervision of an expert clinician; (e) a need for the patient to experience that nurses do care, i.e. experience empathy, during the complete therapeutic programme including the period of special supervision; and (f) a need for further research regarding the patient's perception of nursing care experienced following a failed suicidal attempt.

Adolescent↗

An analytical framework of physician productivity and variation in utilization.

The utilization of medical services by patients is an important determinant of doctor productivity, but this factor does not appear to have been given much attention in previous studies. In order to answer the question of why is there a wide variation in doctor output at low level medical facilities in China, an analytical framework of doctor productivity and utilization is developed. The simulation model is used to produce data that can be analyzed by such a framework. Great uncertainty about patient flows is one reason for the average lower and varying doctor productivity in lower level health facilities. Until uncertainty can be reduced, more flexibility is needed at the lower level to cope with changing utilization patterns and patient characteristics. The management by doctors of non-patient care activities (preventive programmes, medical research, teaching, and administration) is crucial to any approach to using doctor resources more effectively and efficiently.

Ambulatory Care↗

Regulation of CD3 expression in a protein kinase C isozyme-deficient T-cell line.

Using the T-cell lymphoma line HuT 78, and a clone derived from HuT 78, designated K-4, the role of protein kinase C (PKC) isozymes in the expression of a variety of T-cell surface antigens was investigated. HuT 78 expresses PKC isozymes alpha and beta while K-4 expresses only PKC alpha. Flow cytometric analysis revealed that incubation of HuT 78 cells with phorbol 12-myristate 13-acetate (PMA) results in significant down-regulation of surface expression of CD3. While K-4 cells expressed reduced amounts of CD3, a similar reduction in CD3 expression was not observed when these cells were stimulated with PMA. The regulation of expression of CD11a (LFA-1), CD44, CD45RA and CD45RO and of the class II molecules DR and DP in response to PMA, was similar in both cell lines.

Antigens, Surface↗

Neurofilament expression in human T lymphocytes.

The expression of intermediate filaments in normal cells is mainly determined by their embryonal developmental origin. Flow cytometry using monoclonal antibody RT97 demonstrated that neurofilament was detectable in the human HuT 78 T-cell line and on resting T lymphocytes. Expression was greatly increased on lymphocytes activated for 3 days with phorbol ester. Western blotting confirmed the presence of the 200,000 MW form of neurofilament in T lymphocytes. Stimulation of peripheral blood T cells with phorbol myristate acetate (PMA) or with anti-CD3 monoclonal antibodies resulted in a marked increase in detection of phosphorylated neurofilament on Western blotting. Stimulation of HuT 78 cells with anti-LFA-1 resulted in redistribution of neurofilament from a perinuclear spheroid core into dendritic processes. These data indicate that T cells activated through the T-cell receptor associated complex express an intermediate filament usually associated with neurally derived cells. The finding that neurofilament expression and organization are regulated by T-cell surface molecules suggests a role for this intermediate filament in T-cell function.

Blotting, Western↗

Development and characterization of a protein kinase C beta-isozyme-deficient T-cell line.

In the human T-cell lymphoma line, HuT 78, proliferation and phorbol ester-induced growth arrest and differentiation were inhibited by the protein kinase C (PKC) inhibitor, staurosporine. By contrast, an alternative PKC inhibitor, H-7, inhibited proliferation but not phorbol ester-induced growth arrest. The cell line was found to contain both alpha and beta isoforms of PKC by Western blot techniques. A cell line, K-4, was cloned from HuT 78 in the presence of H-7 and this clone was found to be positive for PKC-alpha only. PKC-beta did not return on cultivation in the absence of H-7. Proliferation of K-4 was insensitive to inhibition with both H-7 and staurosporine. However, phorbol ester-induced growth arrest remained staurosporine sensitive. Phorbol-stimulated IL-2 secretion was minimal in the PKC-beta-deficient cell line. These data suggest that PKC-beta may be a regulatory enzyme for proliferation and stimulated interleukin-2 secretion in HuT 78 cells. Heterogeneity of responses to PKC activation may reflect the use of different isozymes in different intracellular pathways. The K-4 cell line should provide a useful tool in the dissection of involvement of PKC isozymes in cellular function.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Controlled trial of antimycobacterial therapy in Crohn's disease. Clofazimine versus placebo.

In order to study the effect of clofazimine, a powerful antimycobacterial and antiinflammatory agent, 49 patients with active Crohn's disease were randomized to either corticosteroids plus clofazimine 100 mg daily (N = 25) or to steroids and matching placebo (N = 24). A total of 28 patients (58%) went into disease remission (clofazimine 16, placebo 12; P = NS) with a fall in disease activity score from 10.5 +/- 4.4 to 3.3 +/- 3.5. Patients were treated for a further eight months with clofazimine or placebo and 18 of 28 maintained their remission and completed the study (clofazimine 12, placebo 6; P = NS). Side effects were minor and consisted of skin rash and increased pigmentation. Clofazimine as a solitary antimycobacterial agent appears ineffective in inducing remission in Crohn's disease but may have a role in either disease maintenance or combination chemotherapy.

Adult↗

Fluorescent markers for hypoxic cells: a study of nitroaromatic compounds, with fluorescent heterocyclic side chains, that undergo bioreductive binding.

Several novel compounds having both a 2-nitroimidazole nucleus and a fluorescent ring system in their molecular structure were prepared and evaluated as potential fluorescent probes for hypoxia. Bioreduction of nitroimidazoles, which is inhibited by oxygen, is known to lead to binding of bioreductive metabolites to cellular macromolecules and this provides a mechanism for binding the fluorescent moiety to hypoxic cells. These compounds can incorporate a wide range of fluorophors and can therefore be designed to suit the laser-line wavelengths available for excitation of fluorescence in the flow cytometer. Several nitroimidazoles with naphthalimide side chains were rapidly taken up into cells and became concentrated in the cells, thus reducing their concentration in the extracellular medium. This suggests a potential microscopic bioavailability problem with probes of this type when used in vivo as they would become progressively depleted in the extracellular fluid as they diffused from blood vessels, through layers of packed cells in tumors, to the hypoxic cells where they could undergo hypoxia-specific metabolism. Synthesis of nitroimidazoles with coumarin fluorophors led to several potentially useful probes for hypoxia; substituents on the coumarin fluorophor had a marked effect on the cellular fluorescence of these compounds.

Animals↗

Flow cytometric evaluation of hypoxic cells in solid experimental tumours using fluorescence immunodetection.

Numerous methods have been proposed for the detection of hypoxic cells using nitroimidazoles labelled with both radioactive and stable isotopes where the isotopic label becomes bound as a result of reductive metabolism of the nitro group. A new probe for hypoxia, 7-(4'-(2-nitroimidazol-l-yl)-butyl)-theophylline, is described where an immunologically recognisable hapten (theophylline) is covalently linked to a 2-nitroimidazole. Bioreduction of the nitroimidazole leads to binding of bioreductive metabolites, and hence the theophylline side-chain, to intracellular molecules. Immunochemical procedures are then used to stain cells containing the bound theophylline using an FITC-conjugated anti-serum. Flow cytometric analysis of stained cells is facilitated by co-staining cellular DNA, which allows discrimination of single cells in the sample and rejection of cell clumps and debris. The alternative use of an immunoperoxidase-conjugated anti-serum has been used to demonstrate the localisation of hypoxic cells in frozen tumour sections.

Animals↗

One man's meat.

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Abattoirs↗