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Biomedical subjects

M Humphreys

Publications and source records attributed to M Humphreys.

At least 19 recordsLinked to original sources
PubMed2001

Relative lung delivery of fluticasone propionate via large volume spacer or nebuliser in healthy volunteers.

OBJECTIVES: High-dose nebulised fluticasone propionate (FP) has been advocated for use in patients with severe persistent asthma. As there is complete first-pass inactivation of FP for the swallowed fraction, systemic absorption is due solely to its lung bioavailability. We wished to compare the relative lung delivery of FP, using adrenal suppression as a surrogate for the respirable dose, when administered via large volume spacer (FP-spacer) or nebuliser (FP-neb) in healthy adults. METHODS: Fourteen healthy subjects, mean (SEM) age 29.4 +/- 2.6 years, were studied in a placebo-controlled, randomised study with three-way crossover design. Single nominal 2-mg doses of the following were given at 1700 hours in randomised sequence: a. FP-spacer: fluticasone pressurised metered dose inhaler (as Flixotide 250 microg ex-valve per actuation), eight puffs via a primed Volumatic 750-ml spacer. b. FP-neb: (as Flixotide Nebule 2 mg/2 ml) via Pari LC Plus nebuliser. c. Placebo nebuliser. Following each dose, measurements were made of corrected 0800-hours urinary cortisol/creatinine ratio (the primary outcome variable) and 0800-hours plasma cortisol. RESULTS: Significant (P<0.05) suppression of both endpoints occurred only with FP-spacer, FP-neb being statistically no different from placebo. Geometric mean fold differences between FP-spacer and placebo were 9.8-fold [95% confidence interval (CI) 3.4, 28.8] for urinary cortisol/creatinine and 4.1-fold (95% CI 2.2, 7.5) for plasma cortisol. Comparing FP-spacer with FP-neb, these differences were 6.8-fold (95% CI 2.3, 20.0) for urinary cortisol/creatinine and 3.3-fold (95% CI 1.8, 6.0) for plasma cortisol. CONCLUSION: For a 2-mg labelled nominal dose of fluticasone, the spacer produced about a sevenfold higher relative lung dose than the nebuliser. This suggests that a very little of the labelled nebulised dose is respirable. Other factors such as patient preference, cost and compliance will determine the inhaler device that is chosen.

Administration, Inhalation↗
PubMed2001

[Does early high dosage dipyridamole in prevention of secondary stroke induce cardiac events?].

In a post hoc analysis of the European Stroke Prevention Study 2 (ESPS2), we investigated whether dipyridamole given as antiplatelet drug in patients with TIA or stroke increases the risk of cardiac events. ESPS2 was a secondary prevention trial including 6602 patients with TIA or stroke. Patients were randomized into one of four treatment arms: 2 x 25 mg acetylsalicylic acid (ASA), 2 x 200 mg slow release dipyridamole (DP), the combination of DP and ASA and placebo. DP did not result in a higher number of cardiac events, e.g., angina pectoris, myocardial infarction or death. The combination of ASA plus DP was superior to either drug alone in the prevention of strokes.

Administration, Oral↗
PubMed2001

Adenovirus-mediated transfer of p53 and p16(INK4a) results in pancreatic cancer regression in vitro and in vivo.

Pancreatic cancer has a very poor prognosis. Current chemotherapy and radiotherapy regimens are only moderately successful. The tumour suppressor genes p53 and p16(INK4a)encode cell cycle regulatory proteins that are important candidates for gene replacement therapy. Over 80% of pancreatic adenocarcinoma cases lack detectable p16 protein while over 60% contain mutated p53 protein. We used replication-deficient recombinant adenoviruses to reintroduce wild-type p16 and p53 into pancreatic cancer cells in vitro and into subcutaneous pancreatic tumours in an animal model to determine the effect on tumour growth. Significant growth inhibition was observed in all five human pancreatic cell lines with these viruses (P < 0.002) compared with similar control viruses expressing either luciferase or beta-galactosidase. G1 arrest was observed in all cell lines 72 h after infection with Adp16. Infection with Adp53 caused significant levels of apoptosis (P < 0.004). Apoptosis was also observed to a lesser degree (P < 0.03) with the Adp16 vector. Subcutaneous pancreatic tumours, generated in nu-nu mice demonstrated significant growth suppression following injection of Adp53, Adp16 and a combination of both Adp53 and Adp16 (P < 0.0001). These results show that transfer of wild-type p53 and p16 produces significant growth suppression of pancreatic cancer in vitro and in vivo.

Adenoviridae↗
PubMed2001

Cardiac safety in the European Stroke Prevention Study 2 (ESPS2).

The second European Stroke Prevention Study investigated the prevention of stroke and/or death in 6602 patients with transient ischaemic attack or stroke with aspirin (25 mg b.d.), dipyridamole (400 mg b.d.), the combination of aspirin and dipyridamole or placebo. This post hoc analysis investigated cardiac events in patients with coronary heart disease or myocardial infarction (MI) at entry. Dipyridamole did not result in a higher number of cardiac events, e.g. angina pectoris, MI, or death from all causes. The combination of aspirin plus dipyridamole was superior to either drug alone in the prevention of stroke.

Angina Pectoris↗
PubMed1999

The matrix metalloproteinases and their inhibitors in the treatment of pancreatic cancer.

Matrix metalloproteinases (MMPs) are a family of zinc-containing proteolytic enzymes that break down extracellular matrix proteins (ECM) in physiological and pathological conditions. Disruption in the tight control of MMP metabolism occurs in cancer, resulting in excessive destruction of the ECM, neovascularization, tumor spread and metastases. Recent studies have shown that overexpression of MMPs is associated with poor prognosis. Several MMP inhibitors have been developed and preclinical trials have confirmed a reduction in tumor spread and metastases. Marimastat is a broad spectrum inhibitor, and recent published results shows the drug is well tolerated in patients with advanced cancer. Phase II studies which have used marimistat alone or in combination with other cytotoxic agents, have produced encouraging results with improved survival. Phase III trials are now underway for the use of marimastat in advanced pancreatic cancer and as an adjuvant therapy in patients following resection of pancreatic cancer.

Animals↗
PubMed1998

Consultant psychiatrists' knowledge of mental health legislation in Scotland.

There has been increasing concern recently over an apparent lack of knowledge of mental health law among psychiatrists and other medical practitioners involved in its use. This has been particularly highlighted by the introduction of new and complex legislation intended to facilitate care in the community. As a result of findings from previous studies of other groups of medical practitioners in Scotland, a national survey of consultant psychiatrists working there was undertaken to determine their level of understanding of the statutory provision for the care of the mentally disordered. A purpose-designed instrument was used at interview with 72 consultants chosen at random from all psychiatric specialties. Their knowledge of even the most basic definitions and fundamental areas was limited, with only just over half being able to give the correct title of one relevant piece of legislation and only one in 10 being able to define mental disorder in terms of the Act. Otherwise knowledge was generally patchy. Greater emphasis should be placed upon training in mental health law for consultant psychiatrists in general, as the findings are unlikely to reflect purely localized patterns. Attitudes to the use of compulsory measures also need to be addressed.

Commitment of Persons with Psychiatric Disorders↗
PubMed1998

Water won't run uphill: the New Deal and malaria control in the American South, 1933-1940.

During the 1930s the United States Government poured significant funds into malaria control, via a variety of New Deal agencies. These projects were largely confined to drainage of mosquito-producing wetlands. Malaria had diminished significantly by the early 1940s, and this paper queries whether that reduction was due to the control projects of the thirties, and, if so, whether such projects should be a model for the current developing world, where malaria is a growing problem today. Malaria statistics from the 1930s and 1940s are unreliable, making this assessment, from the outset, complex. Further, the so-called "malaria projects" from the 1930s were, in fact, poorly planned "make-work" enterprises promoted by the Works Projects Administration and its ilk for the creation of unskilled, ditch-digging jobs. The drainage work lacked the oversight of competent engineers (many of them proving, in fact, that water wont's run uphill), and little of the work had permanent impact as the ditches were not maintained. Further, the work was not necessarily concentrated in malarious areas, since the unemployed's distribution did not overlap that of greatest mosquito density. Of the conflicting goals--unemployment relief and malaria control--the former consistently dominated the latter. The results were predictable. The author suggests that the depopulation of the rural south in the late 1930s had more of an impact (albeit indirect and unintended) on the malaria rates than did the large sums spent allegedly for the purpose of malaria control.

Animals↗
PubMed1997

Klinefelter syndrome and non-Hodgkin lymphoma.

Patients with a 47,XXY karyotype (Klinefelter syndrome) appear to have an increased risk of developing cancer, especially male breast cancer and germ cell tumors, but rarely malignant hematologic disorders. We report a patient with a low grade B-cell non-Hodgkin lymphoma with a 47,XXY karyotype in both the tumor and constitutional cells. This is only the 13th reported case of malignant lymphoma in a patient with Klinefelter syndrome. Although some authors postulate that the 47,XXY karyotype may be a predisposing factor in the development of hematological malignancies, the lack of reported cases suggests that such associations may be no more than chance findings.

Aged↗
PubMed1997

Physical restraint of patients in a psychiatric hospital.

Use of physical restraint occurs within British psychiatric hospitals yet there has been little evaluative research on current practice. The present study aims to describe a group of disturbed in-patients who had required physical restraint at some point during the course of their stay in hospital and to classify the reasons for its use. Cases were identified using Case Register data and information obtained from patients' records. In the 48 episodes of physical restraint identified, patients were predominantly schizophrenic (60%), male (67%) and had been restrained because of physical violence to others (44%) or because they were attempting to abscond (31%). Although the majority of patients were compulsorily detained prior to the use of physical restraint, three remained informal. The findings are discussed in the context of the legal justifications for use of restraint. Further research on current practice is required to enable formulation of clear guidelines.

Adult↗
PubMed1997

Characteristics of in-patients transferred to a locked ward in a Scottish psychiatric hospital.

OBJECTIVE: To identify and characterise in-patients transferred from open wards to the locked facility (IPCU) of a psychiatric teaching hospital, and to classify reasons for transfer. DESIGN: Retrospective case note study using the Lothian Psychiatric Case Register. A reason for transfer classification was devised. SETTING: Intensive Psychiatric Care Unit (IPCU) of the Royal Edinburgh Hospital. SUBJECTS: All in-patients transferred from other wards of the Royal Edinburgh Hospital to the IPCU during one year. RESULTS: Over one year there were 131 transfer episodes involving 97 patients. Ninety-eight per cent of episodes could be allocated to one of six categories of reason for transfer, with physical violence to others being commonest (30%). Patients' mean age was 31 years. There was a predominance of schizophrenics (51%) and males (66%). In 20% of transfers, patients were not detained under mental health legislation. Associations emerged between schizophrenia and physical violence, hypomania/mania and generally disruptive behaviour, personality disorder and self harm. In half of all transfers the patient had already been an in-patient for at least 1 month. Fifty-seven per cent of patients were transferred more than once over the preceding five years. Most (90%) transfers originated from acute wards, and patients stayed in the IPCU less than two weeks (70%) before returning to the open wards (23% less than 24 hours). CONCLUSIONS: Local locked wards deal with a range of disturbed behaviour and can be an important component in the spectrum of secure provision. Further evaluative research is required.

Adolescent↗