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Biomedical subjects

P Haddad

Publications and source records attributed to P Haddad.

At least 19 recordsLinked to original sources
PubMed2005

Plants used by the Cree Nation of Eeyou Istchee (Quebec, Canada) for the treatment of diabetes: A novel approach in quantitative ethnobotany.

In the last decade, the Cree Nation of Eeyou Istchee has witnessed a 150% increase in the prevalence of Type II Diabetes (T2D) for people aged over 20 years. Clinical intervention using conventional therapeutic methods has yielded only a limited success within this population. An ethnobotanical survey was carried out to identify potentially antidiabetic plant species used within the traditional pharmacopoeia of the Cree. Interviews were held with 34 Cree Elders using a list of 15 symptoms ranked according to their association to T2D. A total of 18 species were cited during the survey, spanning 9 plant families. Species were prioritized for pharmacological analysis according to a Syndromic Importance Value, based on their frequency of citation by informants and the number and specificity of symptoms for which they were used. Correspondence and clustering analyses were also performed to determine the specificity of association between species and symptoms and the symptom-based correlation between species. A data matrix and species ranking order generated from Cree-specific literature demonstrates significant similarity and correlation to our original matrix and ranking, respectively. This article demonstrates the applicability of various underutilized quantitative tools in ethnobotany, while taking a convincing preliminary step towards a therapy more in harmony with Cree culture and lifestyle.

Cluster Analysis↗
PubMed2005

Factors influencing the use of single vs multiple fractions of palliative radiotherapy for bone metastases: a 5-year review.

AIMS: Evidence from a number of randomised trials and meta-analyses supports the use of single-fraction radiotherapy for the palliation of painful bone metastases. This study explores patient and treatment factors that influence the choice of single compared with multiple-fraction radiotherapy for the treatment of bone metastases in clinical practice. MATERIALS AND METHODS: The Princess Margaret Hospital Palliative Radiation Oncology Program Database served as the basis for our report. All courses of treatment delivered for bone metastases were extracted. Courses were classified into single or multiple fractions. Clinical characteristics were compared between the two groups. RESULTS: Between 1998 and 2002, 882 courses of radiotherapy were delivered for the treatment of bone metastases, of which 283 (32%) were a single fraction. The proportion of single-fraction treatments was 37% in 1998, 30% in 1999 and 43% in 2000, but dropped to 26% and 28% in 2001 and 2002, respectively (P = 0.02). Patients treated with single fractions were significantly older (68 +/- 12 years vs 64 +/- 12 years), and had more weight loss and poor performance status. Single fractions included 20% of treatments in palliative irradiation of the spine, 36% in the pelvis and long bones, and 59% in the chest wall (P < 0.001). There was no significant difference in patients' gender, primary cancers, number of metastatic sites, treating physicians, enrollment in a clinical trial and general radiotherapy waiting time in our department. Multivariate analysis indicated age (P = 0.001), performance status (P < 0.001), anatomical site (P < 0.001) and year of radiotherapy (P = 0.006) as significant. CONCLUSION: One-third of palliative radiotherapy courses for bone metastases in our programme were given as single fractions. Performance status, age and anatomical site were significant factors affecting single compared with multiple fractionation. The variation in the use of single fractions over time may reflect the dynamic process of interpretation and application of evidence from clinical trials to practice.

Aged↗
PubMed2004

Computed tomographic simulation in palliative radiotherapy: the Princess Margaret Hospital experience.

AIM: To examine the pattern of palliative radiation planning and the use of computed tomographic simulation (CTSIM) for this purpose. MATERIALS AND METHODS: We reviewed our department's external radiotherapy database for all courses of treatment with a palliative intent during the period of April to June 2002. Patient characteristics and treatment details were compared based on whether CTSIM had been used or not. RESULTS: During the above period, 593 courses of external radiation treatment were delivered with palliative intent in our department. Of these, 100 treatments (17%) were planned with the help of CTSIM. The mean age of patients with CTSIM (62.9 years) was not significantly different with the patients planned without CTSIM (63.6 years). CTSIM use varied by treatment location, being highest in mediastinum/oesophagus (48%) and pancreas/stomach (47%) treatments, and lowest in spine (6%), lung (3%) and long bones (4%) (P < 0.01). Only 3% of palliative treatments without CTSIM were prescribed using multiple/complex fields (all field arrangements more complex than a single field or two opposed parallel fields). Although significantly higher (P < 0.001), this proportion was also only 24% in the cases planned with CTSIM. Only 12% of treatments without CTSIM were prescribed with more than 5 fractions, whereas 32% of CT-simulated treatments included more than 5 fractions (P < 0.001). CONCLUSION: CTSIM was used much less frequently in our department's palliative radiotherapy compared with its use in radical treatments. The relatively low rate of multiple/complex fields planned in CT-simulated cases suggested that CTSIM was mostly used to improve tumour localisation. The optimal role of CTSIM in palliative radiotherapy will most probably evolve, based on an enhanced understanding of the implications from improved localisation and optimal planning techniques on clinical outcomes, patient convenience and resource accessibility.

Aged↗
PubMed2003

Supportive care management of brain metastases: what is known and what we need to know. Conference proceedings of the National Cancer Institute of Canada (NCIC) Workshop on Symptom Control in Radiation Oncology.

OBJECTIVES: To review the results of published randomised controlled trials in the treatment of brain metastases and, from the knowledge gained from these trials, to identify potential study questions. MATERIALS AND METHODS: The literature was searched for randomised controlled trials that dealt with the management of brain metastases. Potential research questions were identified on the basis of the results of the literature review. RESULTS: A number of research questions were identified. In the context of the NCIC Symptom Control Group, a trial of supportive care alone vs supportive care and whole-brain radiotherapy (WBRT) in a subset of patients with the diagnosis of brain metastases was deemed to be of highest priority. We discussed a number of issues relating to the feasibility of such a trial. CONCLUSIONS: The optimal management of brain metastases remains elusive. Despite the results of numerous randomised controlled trials, many questions remain unanswered. The magnitude of benefit using WBRT above supportive care alone is uncertain. A trial of supportive care alone vs supportive care and WBRT may be successful once target population, feasibility and methodological issues are thoroughly solved.

Brain Neoplasms↗
PubMed2002

Improved assessment of T-cell receptor (TCR) VB repertoire in clinical specimens: combination of TCR-CDR3 spectratyping with flow cytometry-based TCR VB frequency analysis.

Antigen-specific T-cell responses may be described by combining three categories: (i) the specificity and effector functions of a T-cell population, (ii) the quantity of T-cell responses (i.e., the number of responding T cells within the CD4/CD8 population), and (iii) the "quality" of T cells (defined by the T-cell receptor [TCR] structure). Several methods to measure T-cell responses are now available including evaluation of T-cell precursors using limiting dilution, the enzyme-linked immunospot assay, ex vivo TCR variable (v)-segment analysis determined by flow cytometry, and TCR-CDR3 length analysis (spectratyping), as well as identification of peptide-specific T cells using major histocompatibility complex (MHC) class I tetramers containing appropriate peptides. Until now, only a limited set of MHC-peptide complexes have been available as tetramer complexes. We demonstrate that CD8(+) or CD4(+) T cells in patients with cancer can be molecularly defined using a combination of spectratyping (TCR structure and "molecular composition") plus the implementation of an antibody panel directed against 21 individual VB TCR chains ("quantity" of T-cell families). This approach is instrumental in defining and comparing the magnitudes of CD4(+) or CD8(+) T-cell responses over time in individual patients, in comparing the TCR VA and VB repertoire in different anatomic compartments, and in comparing the TCR VA-VB diversity with that in normal healthy controls. This method provides the means of objectively defining and comparing the TCR repertoire in patients undergoing vaccination protocols and underlines the necessity to calibrate the TCR-CDR3 analysis with a qualitative assessment of individual TCR VB families.

CD4-Positive T-Lymphocytes↗
PubMed2000

Systemic lupus erythematosus presenting as mania.

OBJECTIVE: Psychiatric manifestations of systemic lupus erythematosus (SLE) are well recognized but usually occur in the later stages of the illness, with organic syndromes being the most common. This case highlights the fact that SLE can present with mania. METHOD: Single case report. RESULTS: A 32-year-old woman was admitted to hospital with her first manic illness. Physical examination and investigations revealed her to be suffering from SLE although this had not been previously diagnosed. Her physical and psychiatric symptoms settled rapidly following treatment with prednisolone and chlorpromazine. CONCLUSION: The case emphasizes the polymorphous manifestations of SLE and the importance of considering physical disorders in patients with a first episode of psychosis.

Adult↗
PubMed2000

Compliance with antidepressant therapy and antidepressant discontinuation symptoms.

OBJECTIVE: Compliance with antidepressant medication is important in order to achieve all the goals of antidepressant therapy. These goals include symptom resolution, restoration of normal functioning and prevention of relapse or recurrent episodes. METHOD: We discuss compliance and review adverse symptoms that may occur when antidepressant treatment is abruptly discontinued or interrupted. RESULTS: The physician's role in managing compliance includes preventing or minimizing the risk for discontinuation symptoms, counselling patients regarding the risk for symptoms if doses are missed and choosing pharmacotherapy that is forgiving of non-compliance. Physicians also need to recognize the symptoms of discontinuation syndrome in order to differentiate patients who are non-compliant from patients who require a dosage adjustment or adjunctive therapy. Finally, physicians need to understand how to treat discontinuation symptoms when they do occur. CONCLUSION: Since published data indicate that between 30% and 60% of patients do not take their medications as prescribed, non-adherence to antidepressant medication is likely to be a significant clinical issue in the management of many patients.

Antidepressive Agents, Tricyclic↗
PubMed1999

Cytochrome P-450 content and activity after cold storage of rat hepatocytes in university of wisconsin and sodium-lactobionate-sucrose solutions.

We compared the capacity of University of Wisconsin (UW) and of sodium-lactobionate-sucrose (SLS) hypothermic preservation solutions to maintain the integrity of the hepatic cytochrome P-450-dependent mono-oxygenase system. Isolated rat hepatocytes were stored for 0, 10, 24, and 48 hours in UW or SLS solution and were subsequently cultured shortly at 37 degrees C. Cell viability declined slightly but significantly in a time-dependent manner during cold preservation in either UW or SLS solution, and warm culture exacerbated this effect. Total cytochrome P-450 declined gradually after cold preservation and warm culture to reach values of 70% and 52% of unstored controls in cells preserved for 24 and 48 hours in cold UW solution, respectively. Storage in cold SLS solution yielded a similar decrease to 79% and 59% of unstored controls for the equivalent preservation times. Cytochrome P-450 activity was assessed by the metabolism of theophylline after various cold preservation times in UW or SLS solutions. Production of the major metabolite 1,3-dimethyluric acid was not significantly affected by extended cold preservation periods in either UW or SLS solutions. Similarly, the amount of residual theophylline remained stable in all groups, suggesting that alternative metabolic routes were not modified. These studies show that cold preservation in SLS solution is as effective as that in UW solution in terms of cell viability, cytochrome P-450 content, and activity toward theophylline. In addition, the significant reduction in cytochrome P-450 in conjunction with unaffected theophylline disposition suggests that certain cytochrome P-450 isoforms are specifically damaged by cold preservation and rewarming.

Adenosine↗
PubMed1999

Changes in intracellular calcium induced by acute hypothermia in parenchymal, endothelial, and Kupffer cells of the rat liver.

Disturbances in intracellular calcium have been implicated in liver graft damage after cold preservation and warm reperfusion. Despite improvements noted with the use of calcium channel blockers, such as nisoldipine, the exact nature and cellular basis of the presumed changes in intracellular calcium as well as the actual target of these blockers remain unclear. Isolated rat parenchymal, endothelial, and Kupffer cells were cultured and changes in intracellular calcium measured in vitro after acute hypothermia (5-8 degrees C) by fluorescence imaging using FURA-2. Between 50 and 80% of parenchymal, endothelial, and Kupffer cells exhibited significant increases in baseline calcium that were gradual and sustained for the duration of acute hypothermia. Removal of extracellular calcium completely abolished the positive response of hepatocytes and diminished the proportion of responding endothelial and Kupffer cells. The calcium channel blocker nisoldipine (1 microM) slightly diminished the proportion of positive responders in parenchymal but not in endothelial or Kupffer cells. However, nisoldipine did not modify the amplitude of the calcium rise in responding cells of all types. Acute hypothermia causes calcium influx into a majority of parenchymal, endothelial, and Kupffer cells. Nisoldipine does not effectively prevent these changes in intracellular calcium. Pathways of calcium entry resistant to the drug or other than voltage-dependent calcium channels may thus be involved.

Animals↗
PubMed1999

Do antidepressants have any potential to cause addiction?

Addiction/dependence is a syndrome in which the hallmark is a compulsive pattern of drug use. Most authorities do not regard antidepressants as causing addiction but this has been challenged. This debate is explored drawing on case reports and related clinical and pharmacological data. An extensive literature review identified 21 English language case reports of antidepressant addiction (DSM-IV 'substance dependence' criteria) published since 1963. Sixteen involved tranylcypromine or amineptine and may reflect their dopaminergic and stimulant properties. Subject characteristics included male sex (14/21), personality problems (10/21) and prior substance misuse (14/21). Withdrawal or discontinuation symptoms have long been recognized with antidepressants but other features of addiction such as tolerance and compulsive use are exceptionally rare. Common clinical problems are patients taking subtherapeutic dosages and prematurely stopping antidepressants. The pharmacodynamic profiles of most antidepressants and the absence of acute 'desirable' effects make addiction theoretically unlikely. It is concluded that, with the exception of tranylcypromine and amineptine, antidepressants do not have a clinically significant liability to cause addiction. Tranylcypromine and amineptine should be avoided in those with a history of substance misuse. Patients prescribed other antidepressants should be told that they are not addictive.

Antidepressive Agents↗
PubMed1999

Modulation of liver cell membrane NHE-1, Na+-K+ ATPase, and GLUT-2 protein content after cold preservation and rewarming.

Liver cell pH and volume regulation are perturbed by prolonged cold storage in University of Wisconsin solution and subsequent rewarming, but the molecular basis of this effect remains unknown. We prepared membranes from hepatocytes subjected to variable periods of cold preservation with or without subsequent rewarming and probed them by Western blotting with specific antibodies against the Na+ -H+ exchanger isoform NHE-1 and the Na+ -K+ ATPase alpha subunit. Results were compared with the content of GLUT-2, an abundant basolateral protein. NHE-1 decreased significantly as cold preservation times exceeded 10 h. Subsequent rewarming by short-term culture at 37 degrees C did not further reduce this parameter. On the other hand, expression of Na+ -K+ ATPase remained stable during cold storage times lasting up to 48 h, whereas rewarming resulted in a dramatic reduction in cells cold preserved beyond 10 h. In contrast, the membrane content of GLUT-2 was unaffected by cold preservation with or without subsequent rewarming. The results indicate that cold storage and rewarming respectively and selectively modulate the expression of specific hepatocellular membrane transport proteins.

Animals↗