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Biomedical subjects

B Lord

Publications and source records attributed to B Lord.

13 recordsLinked to original sources
PubMed2006

Histamine H3 receptor antagonists: from target identification to drug leads.

The successful cloning and functional expression of the histamine H(3) receptor in the late 1990 s has greatly facilitated our efforts to identify small molecule, non-imidazole based compounds to permit the evaluation of H(3) antagonists in models of CNS disorders. High-throughput screening identified several series of lead compounds, including a series of imidazopyridines, which led to JNJ-6379490, a compound with high affinity for the human H(3) receptor. Analysis of structural features common to several series of non-imidazole H(3) receptor ligands resulted in a pharmacophore model. This model led to the design of JNJ-5207852, a diamine-based H(3) antagonist with good in vitro and in vivo efficacy but with an undesirable long half-life. However, further modifications of the template provided an understanding of the effect of structural modifications on pharmacokinetic properties, ultimately affording several additional series of compounds including JNJ-10181457, a compound with an improved pharmacokinetic profile. These compounds allowed in vivo pharmacological evaluation to show that H(3) antagonists promote wakefulness, but unlike modafinil and classical psychostimultants, they do not increase locomotor activity or produce any alteration of the EEG power spectral activity in rats. H(3) antagonists also increase extracellular acetylcholine and norepinephrine but not dopamine in rat frontal cortex and show efficacy in various models of learning-memory deficit. In addition, cFos immunoreactivity studies show H(3) antagonists activate neuronal cells in restricted rat brain regions in contrast to widespread activation after modafinil or amphetamine treatment. Therefore, H(3) antagonists are promising clinical candidates for the treatment of excessive day time sleepiness and/or cognitive disorders.

Animals↗
PubMed2004

Acute wake-promoting actions of JNJ-5207852, a novel, diamine-based H3 antagonist.

1 1-[4-(3-piperidin-1-yl-propoxy)-benzyl]-piperidine (JNJ-5207852) is a novel, non-imidazole histamine H3 receptor antagonist, with high affinity at the rat (pKi=8.9) and human (pKi=9.24) H3 receptor. JNJ-5207852 is selective for the H3 receptor, with negligible binding to other receptors, transporters and ion channels at 1 microm. 2 JNJ-5207852 readily penetrates the brain tissue after subcutaneous (s.c.) administration, as determined by ex vivo autoradiography (ED50 of 0.13 mg kg(-1) in mice). In vitro autoradiography with 3H-JNJ-5207852 in mouse brain slices shows a binding pattern identical to that of 3H-R-alpha-methylhistamine, with high specific binding in the cortex, striatum and hypothalamus. No specific binding of 3H-JNJ-5207852 was observed in brains of H3 receptor knockout mice. 3 In mice and rats, JNJ-5207852 (1-10 mg kg(-1) s.c.) increases time spent awake and decreases REM sleep and slow-wave sleep, but fails to have an effect on wakefulness or sleep in H3 receptor knockout mice. No rebound hypersomnolence, as measured by slow-wave delta power, is observed. The wake-promoting effects of this H3 receptor antagonist are not associated with hypermotility. 4 A 4-week daily treatment of mice with JNJ-5207852 (10 mg kg(-1) i.p.) did not lead to a change in body weight, possibly due to the compound being a neutral antagonist at the H3 receptor. 5 JNJ-5207852 is extensively absorbed after oral administration and reaches high brain levels. 6 The data indicate that JNJ-5207852 is a novel, potent and selective H3 antagonist with good in vitro and in vivo efficacy, and confirm the wake-promoting effects of H3 receptor antagonists.

Administration, Oral↗
PubMed2001

The development of an Australian national classification system for social work practice in health care.

Australian Social Work, over recent years, has been challenged to develop a standardised and accurate classification system for social work interventions. The need for such a system arose through changes in funding arrangements based on the Diagnosis Related Groups (DRGs) treated within hospitals. In Australian hospitals, the mix of DRGs treated became known as its 'casemix.' These new funding arrangements made it necessary for Social Work to classify and measure activity with each patient to ensure continuing resource allocation to social work services in hospitals. A national Casemix Network was formed under the auspice of the Australian Association of Social Workers to develop a classification system. The Network worked collaboratively with other allied health professions to produce a generic framework for professional activities and also developed a classification of social work interventions. These activity classifications have been incorporated into procedure coding in Australian hospitals. The challenges associated with casemix funding required Social Work to address a number of philosophical and methodological issues related to classification of professional activities to ensure an outcome that recognised the unique contribution of Social Work to health care.

Australia↗
PubMed2000

Macrophage inflammatory protein 1alpha attenuates the toxic effects of temozolomide in human bone marrow granulocyte-macrophage colony-forming cells.

Macrophage inflammatory protein 1alpha (MIP-1alpha) is a chemokine that may act principally by preventing hemopoietic cells from entering G1, thereby attenuating the cytotoxic effects of cell cycle-specific chemotherapeutic agents. Here we examine the effect of MIP-1alpha on the sensitivity of human granulocyte-macrophage hemopoietic progenitor cells (granulocyte-macrophage colony-forming cells; GM-CFCs) with the cytotoxic effects of antitumor agents that act mainly via alkylation at the O6 position of guanine in DNA. Mononuclear cell preparations from human bone marrow were used in an in vitro GM-CFC colony-forming assay. The GM-CFC survival from individual patients displayed a range of sensitivities to the methylating agent temozolomide [(Tz) 20-55% survival at 10 microg/ml Tz]. However, in all 16 cases, MIP-1alpha (50 ng/ml) protected against GM-CFC killing: survival in the presence of MIP-1alpha ranged from 65-97% at 10 microg/ml Tz, with GM-CFCs being 1.5-4.5-fold more resistant than control cells from the same patient. The highest levels of protection were seen in the GM-CFCs with the highest sensitivity in the absence of MIP-1alpha. Similar degrees of protection were seen for the methylating agent streptozotocin, but no protection was detected for the chloroethylating agents carmustine or mitozolomide in the samples for which there was protection against the toxic effects of Tz. Whereas the mechanism of this effect remains to be established, the results may have potential immediate clinical application in the attenuation of hematological toxicity after administration of methylating antitumor agents.

Antineoplastic Agents, Alkylating↗
PubMed1998

Perceptions of social work intervention with bereaved clients: some implications for hospital social work practice.

The study focussed on social work bereavement intervention in a large Australian teaching hospital comparing client and social work perceptions of the service provided. The study involved the completion of a series of questionnaires and client interviews over a three month period. A combination of content and statistical analysis was used to interpret the findings. Eighty-eight percent of clients contacted indicated satisfaction with the social work service received. The results indicated a positive match between clients' and social workers' perceptions of the intervention, and affirmed the role of social work in bereavement care. Seventy percent of clients made recommendations regarding potential improvements to social work services. These recommendations contained four specific suggestions: that social workers be present when the doctor breaks bad news; that additional support be provided in how to talk to doctors; that social workers be involved from the point of admission of the patient; and that a primary social worker remain with the family throughout the hospital stay.

Australia↗
PubMed1997

Phase II trial of rhIL-6 (interleukin-6) prior to and concurrently with VAD (vincristine, doxorubicin and dexamethasone) chemotherapy for patients with multiple myeloma.

We examined the tolerability and safety of interleukin-6 (rhIL-6) when administered prior to and concurrent with vincristine, doxorubicin and dexamethasone (VAD) in patients with progressive multiple myeloma previously treated with VAD alone. Typical rhIL-6-related effects such as fever, chills, acute phase reactions and reversible abnormalities in liver function tests were observed. The study examined whether rhIL-6 predictably modulated indices of myeloma activity. No consistent, predictable change in myeloma-related parameters was documented upon rhIL-6 administration for either 8 days or 11 days prior to and concurrent with VAD. Two patients showed improved sensitivity to VAD chemotherapy when this was administered with rhIL-6. The overall response rate to rhIL-6 and VAD therapy in this study of relapsed and refractory patients was 50%, comparable to our previous experience with VAD alone in this cohort of patients.

Aged↗
PubMed1994

Providing easy access to distributed medical data.

Many hospitals are fragmented along departmental boundaries, leading to islands of information about patients. This makes data integration difficult, and therefore can increase hospital costs and reduce patient care. This paper presents an architecture to provide uniform and transparent access to computerized data and functions available in this kind of heterogeneous computer environment.

Computer Communication Networks↗
PubMed1990

Eccentric nephroscopy for the incarcerated nephrostomy.

Following a percutaneous stone extraction and demonstration of antegrade flow, conventional methods of traction and coaxial dilatation failed to allow removal of a Stamey-Malecot nephrostomy. An eccentric track was created for nephroscopy. Grasping forceps were used to cut the fibrous tissue from the "wings" of the nephrostomy tube to allow its easy withdrawal. The combined approach by the radiologist and urologist safely overcame the fibrous entrapment.

Aged↗
PubMed1988

The fiber caliber of 5-HT immunoreactive axons in the dorsolateral funiculus of the spinal cord of the rat and cat.

Although there is considerable evidence that the analgesic action of electrical brain stimulation is mediated in part by serotonergic (5-HT) axons in the dorsolateral funiculus (DLF) of the spinal cord, studies in the rat have questioned the existence of this pathway. In this study, we used antisera directed against a conjugate of 5-HT and bovine serum albumin (BSA) to identify immunoreactive 5-HT axons in the DLF of the rat and cat. Both light and electron-microscopic studies were performed so that the fiber caliber of the labeled axons could also be determined. We found a rich complement of immunoreactive 5-HT axons in the DLF of both rat and cat. Although these could be seen without difficulty in the normal cat, in the rat it was necessary to make a lesion of the DLF to build up the staining rostrally. Ultrastructural analysis established that almost all of the labeled axons (in rat and cat) were unmyelinated. We conclude that there are indeed 5-HT immunoreactive axons in the DLF of the rat and cat. These presumably derive from neurons of the medullary nucleus raphe magnus (NRM), which have been implicated in the descending controls exerted by opiates and electrical brain stimulation. The results suggest that previous physiological studies of the properties of the opiate-responsive, spinally projecting NRM neurons were not made from those that are 5-HT containing.

Animals↗
PubMed1988

Deoxycytidine, insulin and epidermal growth factor overcome the effect of two natural inhibitors of the haemopoietic system.

The effect of 2'-deoxycytidine on a pluripotent haemopoietic stem cell proliferation inhibitor, as assayed in the mouse spleen colony technique and on the synthetic haemoregulatory pentapeptide (acting predominantly on myeloid determined cells) as assayed in the agar colony technique, was studied. 2'-deoxycytidine was able to overcome the effect of both inhibitors. The inhibition was also blocked by insulin or epidermal growth factor. Since these results are in agreement with those on other cells and other inhibitors, they may describe a more general phenomenon. It is suggested that the mode of action of the inhibitors involves, probably indirectly, interaction with the activity of ribonucleotide reductase.

Animals↗
PubMed1982

Papillary adenocarcinoma of kidney. II. Radiographic and biologic characteristics.

Papillary adenocarcinoma of the kidney is an uncommon variant of renal adenocarcinomas which, on radiographic evaluation, presents characteristically as a predominantly solid, hypovascular or avascular mass. At the present time, surgery is still mandatory to distinguish this lesion from other solid renal lesions. Finally, because of its slow-growing nature, seemingly well-encapsulated appearance, and apparently more favorable biologic prognosis, these patients conceivably might be treated with less radical surgery in selected instances. As demonstrated by one of our patients (Case 1) enucleation is a reasonable alternative, particularly in patients with a solitary kidney, with compromised renal function, or in patients medically incapable of withstanding radical surgery.

Adenocarcinoma, Papillary↗
PubMedDate not supplied

Gender and cancer support group participation.

PURPOSE: Although support groups are offered to many patients who have received a diagnosis of cancer, a majority of patients choose not to participate. This article reports the results of a study comparing the behavior of men diagnosed with prostate cancer and women diagnosed with breast cancer in their responses to invitations to participate in support groups. DESCRIPTION OF STUDY: One hundred thirty women with breast cancer and 87 men with prostate cancer completed a structured telephone interview. The interview included questions about the patients' choices about support group participation. RESULTS: Interview findings showed that men are less likely to join a support group, but those men who do join attend meetings for about 1 year, as do the women who join. Men and women cite essentially the same reasons for participation: to learn more about their diagnosis, to share their, concerns to compare their physical and emotional progress with other individuals. CLINICAL IMPLICATIONS: These results indicate the need for further exploration of effective interventions for men and women who have been diagnosed with prostate and breast cancer, respectively, in an effort to offer support for the difficult psychological and emotional issues associated with their diagnoses. Although more women than men join support groups, the majority of both populations (67% for women, 87% for men) do not attend any support group meetings. Innovative approaches are needed to encourage participation in existing support groups or to design alternative interventions.

Aged↗