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PARKINSN  August 1997, Week 4

PARKINSN August 1997, Week 4

Subject:

Re: PD: Re-post: Excerpts + Abstracts: Selegiline/Deprenyl/Eldepryl

From:

Gary Lesperance <[log in to unmask]>

Reply-To:

Parkinson's Information Exchange <[log in to unmask]>

Date:

Fri, 22 Aug 1997 13:45:11 -0400

Content-Type:

text/plain

Parts/Attachments:

Parts/Attachments

text/plain (396 lines)

At 11:06 AM 8/22/97 -0400, you wrote:
>a supplement of the American Academy of Neurology
>Reprinted in Neurology 1994;44:S1-S52.
>Editors: William Koller, M.D. Ph.D, Dee Silver, M.D., Abraham Lieberman,=
 M.D.
>
>---------------------------------------------------------------------------=
-
>EXCERPT: Young Parkinson's Handbook
>---------------------------------------------------------------------------=
-
>MAO-B inhibitors:
>These drugs work to make the most of the dopamine your brain is still
>producing or is administered to the patient. Dopamine is broken down by an
>enzyme called monoamine oxidase, or MAO for short. MAO exists both outside
>and inside the brain; inside the brain, it is known as MAO-B. Today, a drug
>called selegiline (Eldepryl) is available to inhibit the action of MAO-B,
>therefore increasing the amount of dopamine available in the nigrostriatal
>pathway. More important, by blocking MAO-B, this drug may slow the
>progression of PD.
>
>Edited by Arlette Johnson, Coordinator
>APDA Young Parkinson's Information and Referral Center
>The American Parkinson Disease Association, 1995
>
>---------------------------------------------------------------------------=
-
>EXCERPT: Parkinson's Disease: Hope Through Research
>---------------------------------------------------------------------------=
-
>Selegiline.
>Also known as deprenyl, selegiline has become a commonly used drug for
>parkinson's disease. Recent studies supported by the NINDS have shown that
>the drug delays the need for levodopa therapy by up to a year or more. When
>selegiline is given with levodopa, it appears to enhance and prolong the
>response to levodopa and thus may reduce wearing-off fluctuations. In
>studies with animals, selegiline has been shown to protect the
>dopamine-producing neurons from the toxic effects of MPTP. Selegiline
>inhibits the activity of the enzyme monoamine oxidase B (MAO-B), the enzyme
>that metabolizes dopamine in the brain, delaying the breakdown of naturally
>occurring dopamine and of dopamine formed from levodopa. Dopamine then
>accumulates in the surviving nerve cells. Some physicians, but not all,
>favor starting all parkinsonian patients on selegiline because of its
>possible protective effect. Selegiline is an easy drug to take, although
>side effects may include nausea, orthostatic hypotension, or insomnia (when
>taken late in the day).
>
>This pamphlet was written and published by the National Institute of
>Neurological Disorders and Stroke (NINDS), the United States' leading
>supporter of research on disorders of the brain and nervous system,
>including Parkinson's disease. NINDS, one of the U.S. Government's 17
>National Institutes of Health in Bethesda, Maryland, is part of the Public
>Health Service within the U.S. Department of Health and Human Services.
>
>---------------------------------------------------------------------------=
-
>ABSTRACT: Attempts to obtain neuroprotection in Parkinson's disease.
>---------------------------------------------------------------------------=
-
>It is suggested that oxidant stress is a contributing factor in the
>pathogenesis of Parkinson's disease (PD). Oxidant stress may contribute to
>cell death in PD because oxidative metabolism of dopamine has the potential
>to yield highly reactive and cytotoxic free radicals. Evidence for this
>hypothesis includes: (1) increased dopamine turnover with increased
>hydrogen peroxide formation; (2) decreased glutathione availability; and
>(3) increased reactive iron in the brains of patients with PD. Antioxidant
>therapies might be neuroprotective and could slow the clinical progression
>of the disease whereas metabolites of levodopa therapy may accelerate the
>rate of neuronal degeneration. Laboratory studies demonstrate that both
>selegiline and dopamine agonists can provide neuroprotective benefits.
>Selegiline-treated patients require less levodopa and have a delay in the
>progression of parkinsonian signs and symptoms. Dopamine agonists provide
>antiparkinson benefits and also diminish the need for levodopa.
>
>Neurology 1997 Jul;49(1 Suppl 1):S26-S33
>Olanow CW
>Mount Sinai School of Medicine, New York, NY 10029, USA.
>PMID: 9222272, MUID: 97365445
>
>---------------------------------------------------------------------------=
-
>ABSTRACT: Contemporary approaches to the pharmacotherapeutic management of
>Parkinson's disease: an overview.
>---------------------------------------------------------------------------=
-
>A number of unresolved issues complicate the effective management of
>patients with Parkinson's disease (PD). Chief among these is the role of
>neuroprotective versus symptomatic pharmacologic interventions. Until the
>etiology of PD is further defined, consensus on appropriate management of
>this illness is unlikely. Clinicians may best serve their patients by
>taking a pragmatic approach to the treatment of PD that utilizes
>potentially beneficial interventions in eligible patients. Such an approach
>would incorporate possible neuroprotective (e.g., selegiline, dopamine
>agonists, sustained-release levodopa) and dopamine-sparing (e.g.,
>combination levodopa/dopamine agonist therapy) strategies whenever possible
>while retaining adequate symptomatic control.
>
>Neurology 1997 Jul;49(1 Suppl 1):S2-S9
>Stern MB
>Parkinson's Disease and Movement Disorders Center,
>University of Pennsylvania Health System, Philadelphia, USA.
>PMID: 9222270, MUID: 97365443
>
>---------------------------------------------------------------------------=
-
>ABSTRACT: Deprenyl, excess mortality, and epidemiological traps.
>---------------------------------------------------------------------------=
-
>Compared with the findings for an age-matched group not taking deprenyl, a
>higher risk of mortality in Parkinson's disease patients taking deprenyl
>has recently been reported. Since a biological basis for this observation
>was not apparent, an epidemiological explanation was sought. Expected
>mortality over a 6-year period in four hypothetical age-matched groups was
>determined. Although groups were age matched, ages of individuals within
>the groups varied. Variation of individual ages within each group, without
>affecting the age-match comparability, produced a marked variation in
>expected group mortality. Mortality comparisons between age-matched groups
>can be invalid. This epidemiological trap might account for the recent
>unexplained high mortality observed in a group of Parkinson's disease
>patients taking deprenyl.
>
>Clin Neuropharmacol 1997 Jun;20(3):276-278
>Riggs JE
>Department of Neurology, West Virginia University School of Medicine,
>Morgantown 26506, USA.
>PMID: 9197952, MUID: 97341660
>
>---------------------------------------------------------------------------=
-
>ABSTRACT: Parkinson's disease.
>---------------------------------------------------------------------------=
-
>Parkinson's disease is a common disabling disease of old age. The diagnosis
>of idiopathic Parkinson's disease is based on clinical signs and has poor
>sensitivity, with about 25% of patients confidently diagnosed as having the
>disease actually having other conditions such as multi-system atrophy and
>other parkinsonism-plus syndromes. Benign essential tremor and
>arteriosclerotic pseudo-parkinsonism can easily be confused with
>Parkinson's disease. The cause of Parkinson's disease remains unknown.
>Speculative research highlights the role of oxidative stress and free
>radical mediated damage to dopaminergic cells. Parkinson's disease is the
>one neurodegenerative disorder in which drugs have been demonstrated to be
>of value. There is now a wide variety of drugs and formulations available,
>including anticholinergics, amantidine, L-dopa, dopamine agonists including
>apomorphine, selegiline and soon to be available
>catechol-O-methyltransferase inhibitors. Disabling side-effects of
>treatment, fluctuations, dyskinesias and psychiatric problems require
>strategic use of the drugs available. There is an increasing potential for
>neurosurgical intervention.
>
>Postgrad Med J 1997 May;73(859):257-284
>Playfer JR
>Department of Geriatric Medicine, Royal Liverpool University Hospital, UK.
>PMID: 9196696, MUID: 97340197
>
>---------------------------------------------------------------------------=
-
>ABSTRACT: A dose-ranging study of selegiline in patients with Parkinson's
>disease: effect of platelet monoamine oxidase activity.
>---------------------------------------------------------------------------=
-
>A dose-ranging study of selegiline was performed in patients with
>Parkinson's disease to determine the minimal dosage of the drug able to
>inhibit > or =3D 95% of platelet monoamine oxidase (MAO) activity.=
 Different
>doses of selegiline (5 or 10 mg daily, 10 or 20 mg weekly) were studied in
>four groups of six patients with Parkinson's disease. Platelet MAO activity
>was measured before and after 1 month's treatment with selegiline. The
>doses of 5 or 10 mg daily and 20 mg (i.e., 10 mg x 2) weekly induced a
>complete inhibition of platelet MAO-B activity from day 7 to day 28
>(96.0-99.5%). In contrast, platelet MAO-B inhibition was only 75.9% of the
>basal value after a dosage of 10 mg weekly. These results demonstrate that
>20 mg weekly is the minimal dosage of selegiline able to induce a maximal
>and long-lasting inhibition of platelet MAO-B activity in patients with
>parkinsonism. Further clinical trials are needed to investigate the
>clinical efficacy of this dose.
>
>Mov Disord 1997 May;12(3):293-296
>Andreu N, Damase-Michel C, Senard JM, Rascol O, Montastruc JL
>Laboratoire de Pharmacologie Medicale et Clinique, INSERM U 317, Faculte de
>Medicine, Toulouse, France.=7F
>PMID: 9159721, MUID: 97303396
>
>---------------------------------------------------------------------------=
-
>ABSTRACT: Selegiline as the primary treatment of Parkinson's disease--a=
 long-
>term double-blind study.
>---------------------------------------------------------------------------=
-
>INTRODUCTION: To assess the therapeutic efficacy of selegiline combined
>with levodopa in the long-term treatment of Parkinson's disease (PD).=20
>MATERIAL AND METHODS: A randomized, prospective, double-blind study on 44
>patients with PD needing levodopa therapy after the initial double-blind
>treatment with placebo or selegiline was carried out. The patients were
>followed-up for 5 years under combination therapy.=20
>RESULTS: Selegiline induced a significant (P < 0.001) slowing in the need
>to increase the daily levodopa dose in order to compensate for the
>progression of the disease. After 5 years of combination therapy the mean
>dose of levodopa was on average 320 mg lower in the selegiline group (405
>+/- 59 mg vs 725 +/- 78 mg). The difference in the levodopa doses between
>the two groups increased along with follow-up time, as also the ratio of
>the levodopa doses (placebo/selegiline group). The number of daily levodopa
>doses needed to compensate for the occurrence of motor fluctuations was
>significantly lower in the selegiline group. The parkinsonian disability
>did not differ between the two groups because the clinical condition was
>kept as optimal as possible by adjusting the levodopa dosage. Nine patients
>in the placebo group needed initiation of additional dopaminergic therapy
>in comparison to one in the selegiline group (P =3D 0.004). During the=
 5-year
>follow-up period 11 patients were withdrawn from the selegiline group, 7
>due to adverse events. There was no difference in mortality between the two
>groups.=20
>CONCLUSIONS: Selegiline therapy offers beneficial long-term effets in the
>treatment of PD.
>
>Acta Neurol Scand 1997 Apr;95(4):211-218
>Myllyla VV, Sotaniemi KA, Hakulinen P, Maki-Ikola O, Heinonen EH
>Department of Neurology, Oulu University Hospital, Finland.
>PMID: 9150811, MUID: 97295169
>
>---------------------------------------------------------------------------=
-
>ABSTRACT: Serotonin syndrome and the combined use of deprenyl and an
>antidepressant in Parkinson's disease. Parkinson Study Group.
>---------------------------------------------------------------------------=
-
>The manufacturer of deprenyl (selegeline; Eldepryl) (Somerset
>Pharmaceuticals, Tampa, FL) recently advised physicians to avoid
>prescribing the drug in combination with an antidepressant because of
>potentially serious CNS toxicity that may represent the serotonin syndrome.
>Manifestations of the serotonin syndrome vary but may include changes in
>mental status and motor and autonomic function. To better estimate the
>frequency of the serotonin syndrome in patients with Parkinson's disease
>(PD) treated with deprenyl and an antidepressant, we surveyed all
>investigators in the Parkinson Study Group. Based on estimates provided by
>the 47 investigators (75%) who responded, 4,568 patients were treated with
>the combination of deprenyl and an antidepressant medication. Eleven
>patients (0.24%) were reported to have experienced symptoms possibly
>consistent with the serotonin syndrome. Only two patients (0.04%)
>experienced symptoms considered to be serious. No deaths were reported. We
>also reviewed all published case reports and adverse experiences reported
>to the U.S. Food and Drug Administration and the manufacturer of Eldepryl.
>Available information indicates that serious adverse experiences resulting
>from the combined use of deprenyl and an antidepressant medication in
>patients with PD are quite rare and that the frequency of the true
>"serotonin syndrome" is even rarer.
>
>Neurology 1997 Apr;48(4):1070-1077
>Richard IH, Kurlan R, Tanner C, Factor S, Hubble J, Suchowersky O, Waters C
>University of Rochester Medical Center, NY  14642-8673, USA.
>PMID: 9109902, MUID: 97264030
>
>---------------------------------------------------------------------------=
-
>ABSTRACT: The effects of early selegiline therapy on long-term levodopa
>treatment and parkinsonian disability: an interim analysis of a Norwegian--
>Danish 5-year study. Norwegian-Danish Study Group.
>---------------------------------------------------------------------------=
-
>In this study, we investigated the effects of selegiline on levodopa
>treatment and parkinsonian disability over several years of treatment in
>patients with early Parkinson's disease (PD). The 163 patients were
>randomized to receive either selegiline or placebo in addition to levodopa
>in a double-blind, parallel-group study design, and the patients were to be
>followed up until a defined termination point or for 5 years. All patients
>had previously either never (two thirds) or for < 6 months (one third)
>received levodopa. After 1 year of treatment or at withdrawal from study or
>both, the patients were divided according to specified diagnostic criteria
>into groups of definite, probable, possible, or unlikely PD. The efficacy
>parameters were levodopa therapy, Unified Parkinson's Disease Rating Scale
>(UPDRS) with subscales, and the time to develop wearing-off fluctuations or
>reaching the termination point. Evaluation of efficacy was performed for
>all patients with PD and for patients with a definite and probable disease.
>The results of this study are based on an interim analysis when 80% of the
>163 randomized patients had been followed up for > or =3D 3 years. Nine
>patients were excluded from the study because of protocol violations or
>because the patients were diagnosed as unlikely PD. At the time of interim
>analysis, 39 patients had been withdrawn from the study because of adverse
>effects or their own wish. Eighteen patients had reached the termination
>point, and 97 patients (observation time, 30-54 months) were still in the
>study. Among the patients receiving selegiline, we found a rather stable
>daily levodopa dose during 54 months of therapy, compared with an
>anticipated increase among patients with levodopa monotherapy.
>Concurrently, patients in the selegiline group showed a trend to develop
>less severe parkinsonian disability and a lower frequency of motor
>fluctuations and need for additional antiparkinsonian medication. The
>results of this study indicate that early combination therapy of selegiline
>and levodopa compared with levodopa monotherapy has an increasingly
>favorable impact on the long-term daily levodopa dose and may possibly
>delay the development of disability in PD.
>
>Mov Disord 1997 Mar;12(2):175-182
>Larsen JP, Boas J
>Department of Neurology, Central Hospital of Rogaland, Stavanger, Norway.
>
>PMID: 9087975, MUID: 97242995
>
>---------------------------------------------------------------------------=
-
>ABSTRACT: Selegiline treatment after transient global ischemia in gerbils
>enhances the survival of CA1 pyramidal cells in the hippocampus.
>---------------------------------------------------------------------------=
-
>Selegiline (L-deprenyl) has shown neuroprotective effects in a variety of
>degenerative processes. The present experiments were designed to test
>whether post-ischemia administered selegiline would alleviate delayed
>neuronal death of the gerbil hippocampal pyramidal cells following
>transient global ischemia. Common carotid arteries were occluded for 5 min.
>Saline or selegiline, 0.25 mg/kg s.c., was administered 2 h after the
>ischemia followed by a daily injection for either 3 or 7 days. After
>decapitation, the delayed death of the hippocampal CA1 pyramidal cells was
>assessed using Nissl-stained sections. In situ hybridization was used to
>reveal the expression of hsp70 mRNA 1, 3 or 7 days after the ischemia.
>Animals treated with selegiline for 7 days showed significantly lower
>damage score (scale 0-3: 0, normal; 1, < 10% of the neurons damaged; 2,
>10-50% damaged; 3, > 50% damaged) compared to the saline-treated animals
>1.73 +/- 0.18 and 2.41 +/- 0.16 (mean +/- S.E.M., P =3D 0.0133),
>respectively. A similar trend was found in animals after the 3-day
>treatment: 1.68 +/- 0.32 vs. 2.06 +/- 0.25 (P > 0.5). The expression of
>hsp70 mRNA in the CA1 pyramidal cell layer was strong still 3 days after
>the ischemic insult but vanished by 7 days. Densitometric measurements
>using 14C-plastic standards showed that the intensity of the CA1a hsp70
>signal on the 3rd day correlated negatively to the cell-damage score (r =3D
>-0.72, P < 0.001), suggesting that hsp70 does not serve as a quantitative
>marker for CA1 neuronal injury in this model. Instead, the hsp70 expression
>was associated with improved neuronal survival lasting often longer in
>selegiline-treated animals (P > 0.5). The results show that a low dose of
>selegiline can alleviate the delayed hippocampal neuronal death in gerbils
>when administered 2 h after an ischemic insult.
>
>Brain Res 1997 May 23;757(2):260-267
>Lahtinen H, Koistinaho J, Kauppinen R, Haapalinna A, Keinanen R, Sivenius J
>A.I. Virtanen Institute, University of Kuopio, Finland.
>PMID: 9200755, MUID: 97344228
>
>---------------------------------------------------------------------------=
-
>ABSTRACT: (-)-Deprenyl treatment restores serum insulin-like growth=
 factor-I
>(IGF-I) levels in aged rats to young rat level.
>---------------------------------------------------------------------------=
-
>We studied the effects of treatment with (-)-deprenyl, a monoamine oxidase
>B inhibitor, on plasma levels of insulin-like growth factor-I (IGF-I) (as
>indicator of growth hormone (GH) secretion), levels of monoamines and their
>metabolites, and the activity and content of tyrosine hydroxylase - the
>rate-limiting enzyme in the biosynthesis of catecholamines - in the
>hypothalamus and hypophysis of old male rats. Male Wistar rats (22 months
>old) were treated with 2 mg deprenyl/kg body weight s.c. three times a week
>for 2 months. At the end of the treatment period, blood was collected for
>measurement of plasma IGF-I levels by radioimmunoassay (RIA). The
>concentrations of dopamine, serotonin (5-HT) and their main metabolites
>were determined by high performance liquid chromatography (HPLC) with
>electrochemical detection, and the tyrosine hydroxylase content in
>hypothalamus and hypophysis was determined by enzyme-linked immunoabsorbent
>assay (ELISA). (-)-Deprenyl treatment produced a pronounced increase in
>dopamine and 5-HT in both the hypothalamus and hypophysis (P < 0.01). The
>main dopaminergic metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC),
>decreased in hypothalamus but not in hypophysis, and treatment had no
>effect on the concentration of 5-hydroxyindole-3-acetic acid (5-HIAA). The
>tyrosine hydroxylase activity and tyrosine hydroxylase content increased in
>hypothalamus and hypophysis (P < 0.05). In the hypophysis the increase in
>tyrosine hydroxylase activity was consistent with the increase in tyrosine
>hydroxylase amount. Moreover, (-)-deprenyl treatment restored the IGF-I
>plasma levels in old rats to a concentration similar to those found in
>young animals. Postulated anti-aging effects of (-)-deprenyl could hence be
>due to restoration of hypothalamic hormones such as GH.
>
>Eur J Pharmacol 1997 May 30;327(2-3):215-220
>De la Cruz CP, Revilla E, Rodriguez-Gomez JA, Vizuete ML, Cano J, Machado A
>Departamento de Bioquimica, Bromatologia y Toxicologia, Facultad de
>Farmacia, Universidad de Sevilla, Spain.
>PMID: 9200562, MUID: 97344035
>
>---------------------------------------------------------------------------=
-
>
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>
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President, SiteGen, Inc.
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(voice) 888-748-3436 or 414-832-1113
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September 2013, Week 4
September 2013, Week 3
September 2013, Week 2
September 2013, Week 1
August 2013, Week 5
August 2013, Week 4
August 2013, Week 3
August 2013, Week 2
August 2013, Week 1
July 2013, Week 5
July 2013, Week 4
July 2013, Week 3
July 2013, Week 2
July 2013, Week 1
June 2013, Week 5
June 2013, Week 4
June 2013, Week 3
June 2013, Week 2
June 2013, Week 1
May 2013, Week 5
May 2013, Week 4
May 2013, Week 3
May 2013, Week 2
May 2013, Week 1
April 2013, Week 5
April 2013, Week 4
April 2013, Week 3
April 2013, Week 2
April 2013, Week 1
March 2013, Week 5
March 2013, Week 4
March 2013, Week 3
March 2013, Week 2
March 2013, Week 1
February 2013, Week 4
February 2013, Week 3
February 2013, Week 2
February 2013, Week 1
January 2013, Week 5
January 2013, Week 3
January 2013, Week 2
January 2013, Week 1
December 2012, Week 5
December 2012, Week 4
December 2012, Week 3
December 2012, Week 2
December 2012, Week 1
November 2012, Week 5
November 2012, Week 3
November 2012, Week 2
November 2012, Week 1
October 2012, Week 5
October 2012, Week 4
October 2012, Week 3
October 2012, Week 2
October 2012, Week 1
September 2012, Week 5
September 2012, Week 4
September 2012, Week 3
September 2012, Week 2
September 2012, Week 1
August 2012, Week 5
August 2012, Week 4
August 2012, Week 3
August 2012, Week 2
August 2012, Week 1
July 2012, Week 5
July 2012, Week 4
July 2012, Week 3
July 2012, Week 2
July 2012, Week 1
June 2012, Week 5
June 2012, Week 4
June 2012, Week 3
June 2012, Week 2
June 2012, Week 1
May 2012, Week 5
May 2012, Week 4
May 2012, Week 3
May 2012, Week 2
May 2012, Week 1
April 2012, Week 5
April 2012, Week 4
April 2012, Week 3
April 2012, Week 2
April 2012, Week 1
March 2012, Week 5
March 2012, Week 4
March 2012, Week 3
March 2012, Week 2
March 2012, Week 1
February 2012, Week 5
February 2012, Week 4
February 2012, Week 3
February 2012, Week 2
February 2012, Week 1
January 2012, Week 5
January 2012, Week 4
January 2012, Week 3
January 2012, Week 2
January 2012, Week 1
December 2011, Week 5
December 2011, Week 4
December 2011, Week 3
December 2011, Week 2
December 2011, Week 1
November 2011, Week 5
November 2011, Week 4
November 2011, Week 3
November 2011, Week 2
November 2011, Week 1
October 2011, Week 5
October 2011, Week 4
October 2011, Week 3
October 2011, Week 2
October 2011, Week 1
September 2011, Week 5
September 2011, Week 4
September 2011, Week 3
September 2011, Week 2
September 2011, Week 1
August 2011, Week 5
August 2011, Week 4
August 2011, Week 3
August 2011, Week 2
August 2011, Week 1
July 2011, Week 5
July 2011, Week 4
July 2011, Week 3
July 2011, Week 2
July 2011, Week 1
June 2011, Week 5
June 2011, Week 4
June 2011, Week 3
June 2011, Week 2
June 2011, Week 1
May 2011, Week 5
May 2011, Week 4
May 2011, Week 3
May 2011, Week 2
May 2011, Week 1
April 2011, Week 5
April 2011, Week 4
April 2011, Week 3
April 2011, Week 2
April 2011, Week 1
March 2011, Week 5
March 2011, Week 4
March 2011, Week 3
March 2011, Week 2
March 2011, Week 1
February 2011, Week 4
February 2011, Week 3
February 2011, Week 2
February 2011, Week 1
January 2011, Week 5
January 2011, Week 4
January 2011, Week 3
January 2011, Week 2
January 2011, Week 1
December 2010, Week 5
December 2010, Week 4
December 2010, Week 3
December 2010, Week 2
December 2010, Week 1
November 2010, Week 5
November 2010, Week 4
November 2010, Week 3
November 2010, Week 2
November 2010, Week 1
October 2010, Week 5
October 2010, Week 4
October 2010, Week 3
October 2010, Week 2
October 2010, Week 1
September 2010, Week 5
September 2010, Week 4
September 2010, Week 3
September 2010, Week 2
September 2010, Week 1
August 2010, Week 5
August 2010, Week 4
August 2010, Week 3
August 2010, Week 2
August 2010, Week 1
July 2010, Week 5
July 2010, Week 4
July 2010, Week 3
July 2010, Week 2
July 2010, Week 1
June 2010, Week 5
June 2010, Week 4
June 2010, Week 3
June 2010, Week 2
June 2010, Week 1
May 2010, Week 5
May 2010, Week 4
May 2010, Week 3
May 2010, Week 2
May 2010, Week 1
April 2010, Week 5
April 2010, Week 4
April 2010, Week 3
April 2010, Week 2
April 2010, Week 1
March 2010, Week 5
March 2010, Week 4
March 2010, Week 3
March 2010, Week 2
March 2010, Week 1
February 2010, Week 4
February 2010, Week 3
February 2010, Week 2
February 2010, Week 1
January 2010, Week 5
January 2010, Week 4
January 2010, Week 3
January 2010, Week 2
January 2010, Week 1
December 2009, Week 5
December 2009, Week 4
December 2009, Week 3
December 2009, Week 2
December 2009, Week 1
November 2009, Week 5
November 2009, Week 4
November 2009, Week 3
November 2009, Week 2
November 2009, Week 1
October 2009, Week 5
October 2009, Week 4
October 2009, Week 3
October 2009, Week 2
October 2009, Week 1
September 2009, Week 5
September 2009, Week 4
September 2009, Week 3
September 2009, Week 2
September 2009, Week 1
August 2009, Week 5
August 2009, Week 4
August 2009, Week 3
August 2009, Week 2
August 2009, Week 1
July 2009, Week 5
July 2009, Week 4
July 2009, Week 3
July 2009, Week 2
July 2009, Week 1
June 2009, Week 5
June 2009, Week 4
June 2009, Week 3
June 2009, Week 2
June 2009, Week 1
May 2009, Week 5
May 2009, Week 4
May 2009, Week 3
May 2009, Week 2
May 2009, Week 1
April 2009, Week 5
April 2009, Week 4
April 2009, Week 3
April 2009, Week 2
April 2009, Week 1
March 2009, Week 5
March 2009, Week 4
March 2009, Week 3
March 2009, Week 2
March 2009, Week 1
February 2009, Week 4
February 2009, Week 3
February 2009, Week 2
February 2009, Week 1
January 2009, Week 5
January 2009, Week 4
January 2009, Week 3
January 2009, Week 2
January 2009, Week 1
December 2008, Week 5
December 2008, Week 4
December 2008, Week 3
December 2008, Week 2
December 2008, Week 1
November 2008, Week 5
November 2008, Week 4
November 2008, Week 3
November 2008, Week 2
November 2008, Week 1
October 2008, Week 5
October 2008, Week 4
October 2008, Week 3
October 2008, Week 2
October 2008, Week 1
September 2008, Week 5
September 2008, Week 4
September 2008, Week 3
September 2008, Week 2
September 2008, Week 1
August 2008, Week 5
August 2008, Week 4
August 2008, Week 3
August 2008, Week 2
August 2008, Week 1
July 2008, Week 5
July 2008, Week 4
July 2008, Week 3
July 2008, Week 2
July 2008, Week 1
June 2008, Week 5
June 2008, Week 4
June 2008, Week 3
June 2008, Week 2
June 2008, Week 1
May 2008, Week 5
May 2008, Week 4
May 2008, Week 3
May 2008, Week 2
May 2008, Week 1
April 2008, Week 5
April 2008, Week 4
April 2008, Week 3
April 2008, Week 2
April 2008, Week 1
March 2008, Week 5
March 2008, Week 4
March 2008, Week 3
March 2008, Week 2
March 2008, Week 1
February 2008, Week 5
February 2008, Week 4
February 2008, Week 3
February 2008, Week 2
February 2008, Week 1
January 2008, Week 5
January 2008, Week 4
January 2008, Week 3
January 2008, Week 2
January 2008, Week 1
December 2007, Week 5
December 2007, Week 4
December 2007, Week 3
December 2007, Week 2
December 2007, Week 1
November 2007, Week 5
November 2007, Week 4
November 2007, Week 3
November 2007, Week 2
November 2007, Week 1
October 2007, Week 5
October 2007, Week 4
October 2007, Week 3
October 2007, Week 2
October 2007, Week 1
September 2007, Week 5
September 2007, Week 4
September 2007, Week 3
September 2007, Week 2
September 2007, Week 1
August 2007, Week 5
August 2007, Week 4
August 2007, Week 3
August 2007, Week 2
August 2007, Week 1
July 2007, Week 5
July 2007, Week 4
July 2007, Week 3
July 2007, Week 2
July 2007, Week 1
June 2007, Week 5
June 2007, Week 4
June 2007, Week 3
June 2007, Week 2
June 2007, Week 1
May 2007, Week 5
May 2007, Week 4
May 2007, Week 3
May 2007, Week 2
May 2007, Week 1
April 2007, Week 5
April 2007, Week 4
April 2007, Week 3
April 2007, Week 2
April 2007, Week 1
March 2007, Week 5
March 2007, Week 4
March 2007, Week 3
March 2007, Week 2
March 2007, Week 1
February 2007, Week 4
February 2007, Week 3
February 2007, Week 2
February 2007, Week 1
January 2007, Week 5
January 2007, Week 4
January 2007, Week 3
January 2007, Week 2
January 2007, Week 1
December 2006, Week 5
December 2006, Week 4
December 2006, Week 3
December 2006, Week 2
December 2006, Week 1
November 2006, Week 5
November 2006, Week 4
November 2006, Week 3
November 2006, Week 2
November 2006, Week 1
October 2006, Week 5
October 2006, Week 4
October 2006, Week 3
October 2006, Week 2
October 2006, Week 1
September 2006, Week 5
September 2006, Week 4
September 2006, Week 3
September 2006, Week 2
September 2006, Week 1
August 2006, Week 5
August 2006, Week 4
August 2006, Week 3
August 2006, Week 2
August 2006, Week 1
July 2006, Week 5
July 2006, Week 4
July 2006, Week 3
July 2006, Week 2
July 2006, Week 1
June 2006, Week 5
June 2006, Week 4
June 2006, Week 3
June 2006, Week 2
June 2006, Week 1
May 2006, Week 5
May 2006, Week 4
May 2006, Week 3
May 2006, Week 2
May 2006, Week 1
April 2006, Week 5
April 2006, Week 4
April 2006, Week 3
April 2006, Week 2
April 2006, Week 1
March 2006, Week 5
March 2006, Week 4
March 2006, Week 3
March 2006, Week 2
March 2006, Week 1
February 2006, Week 4
February 2006, Week 3
February 2006, Week 2
February 2006, Week 1
January 2006, Week 5
January 2006, Week 4
January 2006, Week 3
January 2006, Week 2
January 2006, Week 1
December 2005, Week 5
December 2005, Week 4
December 2005, Week 3
December 2005, Week 2
December 2005, Week 1
November 2005, Week 5
November 2005, Week 4
November 2005, Week 3
November 2005, Week 2
November 2005, Week 1
October 2005, Week 5
October 2005, Week 4
October 2005, Week 3
October 2005, Week 2
October 2005, Week 1
September 2005, Week 5
September 2005, Week 4
September 2005, Week 3
September 2005, Week 2
September 2005, Week 1
August 2005, Week 5
August 2005, Week 4
August 2005, Week 3
August 2005, Week 2
August 2005, Week 1
July 2005, Week 5
July 2005, Week 4
July 2005, Week 3
July 2005, Week 2
July 2005, Week 1
June 2005, Week 5
June 2005, Week 4
June 2005, Week 3
June 2005, Week 2
June 2005, Week 1
May 2005, Week 5
May 2005, Week 4
May 2005, Week 3
May 2005, Week 2
May 2005, Week 1
April 2005, Week 5
April 2005, Week 4
April 2005, Week 3
April 2005, Week 2
April 2005, Week 1
March 2005, Week 5
March 2005, Week 4
March 2005, Week 3
March 2005, Week 2
March 2005, Week 1
February 2005, Week 4
February 2005, Week 3
February 2005, Week 2
February 2005, Week 1
January 2005, Week 5
January 2005, Week 4
January 2005, Week 3
January 2005, Week 2
January 2005, Week 1
December 2004, Week 5
December 2004, Week 4
December 2004, Week 3
December 2004, Week 2
December 2004, Week 1
November 2004, Week 5
November 2004, Week 4
November 2004, Week 3
November 2004, Week 2
November 2004, Week 1
October 2004, Week 5
October 2004, Week 4
October 2004, Week 3
October 2004, Week 2
October 2004, Week 1
September 2004, Week 5
September 2004, Week 4
September 2004, Week 3
September 2004, Week 2
September 2004, Week 1
August 2004, Week 5
August 2004, Week 4
August 2004, Week 3
August 2004, Week 2
August 2004, Week 1
July 2004, Week 5
July 2004, Week 4
July 2004, Week 3
July 2004, Week 2
July 2004, Week 1
June 2004, Week 5
June 2004, Week 4
June 2004, Week 3
June 2004, Week 2
June 2004, Week 1
May 2004, Week 5
May 2004, Week 4
May 2004, Week 3
May 2004, Week 2
May 2004, Week 1
April 2004, Week 5
April 2004, Week 4
April 2004, Week 3
April 2004, Week 2
April 2004, Week 1
March 2004, Week 5
March 2004, Week 4
March 2004, Week 3
March 2004, Week 2
March 2004, Week 1
February 2004, Week 5
February 2004, Week 4
February 2004, Week 3
February 2004, Week 2
February 2004, Week 1
January 2004, Week 5
January 2004, Week 4
January 2004, Week 3
January 2004, Week 2
January 2004, Week 1
December 2003, Week 5
December 2003, Week 4
December 2003, Week 3
December 2003, Week 2
December 2003, Week 1
November 2003, Week 5
November 2003, Week 4
November 2003, Week 3
November 2003, Week 2
November 2003, Week 1
October 2003, Week 5
October 2003, Week 4
October 2003, Week 3
October 2003, Week 2
October 2003, Week 1
September 2003, Week 5
September 2003, Week 4
September 2003, Week 3
September 2003, Week 2
September 2003, Week 1
August 2003, Week 5
August 2003, Week 4
August 2003, Week 3
August 2003, Week 2
August 2003, Week 1
July 2003, Week 5
July 2003, Week 4
July 2003, Week 3
July 2003, Week 2
July 2003, Week 1
June 2003, Week 5
June 2003, Week 4
June 2003, Week 3
June 2003, Week 2
June 2003, Week 1
May 2003, Week 5
May 2003, Week 4
May 2003, Week 3
May 2003, Week 2
May 2003, Week 1
April 2003, Week 5
April 2003, Week 4
April 2003, Week 3
April 2003, Week 2
April 2003, Week 1
March 2003, Week 5
March 2003, Week 4
March 2003, Week 3
March 2003, Week 2
March 2003, Week 1
February 2003, Week 4
February 2003, Week 3
February 2003, Week 2
February 2003, Week 1
January 2003, Week 5
January 2003, Week 4
January 2003, Week 3
January 2003, Week 2
January 2003, Week 1
December 2002, Week 5
December 2002, Week 4
December 2002, Week 3
December 2002, Week 2
December 2002, Week 1
November 2002, Week 5
November 2002, Week 4
November 2002, Week 3
November 2002, Week 2
November 2002, Week 1
October 2002, Week 5
October 2002, Week 4
October 2002, Week 3
October 2002, Week 2
October 2002, Week 1
September 2002, Week 5
September 2002, Week 4
September 2002, Week 3
September 2002, Week 2
September 2002, Week 1
August 2002, Week 5
August 2002, Week 4
August 2002, Week 3
August 2002, Week 2
August 2002, Week 1
July 2002, Week 5
July 2002, Week 4
July 2002, Week 3
July 2002, Week 2
July 2002, Week 1
June 2002, Week 5
June 2002, Week 4
June 2002, Week 3
June 2002, Week 2
June 2002, Week 1
May 2002, Week 5
May 2002, Week 4
May 2002, Week 3
May 2002, Week 2
May 2002, Week 1
April 2002, Week 5
April 2002, Week 4
April 2002, Week 3
April 2002, Week 2
April 2002, Week 1
March 2002, Week 5
March 2002, Week 4
March 2002, Week 3
March 2002, Week 2
March 2002, Week 1
February 2002, Week 4
February 2002, Week 3
February 2002, Week 2
February 2002, Week 1
January 2002, Week 5
January 2002, Week 4
January 2002, Week 3
January 2002, Week 2
January 2002, Week 1
December 2001, Week 5
December 2001, Week 4
December 2001, Week 3
December 2001, Week 2
December 2001, Week 1
November 2001, Week 5
November 2001, Week 4
November 2001, Week 3
November 2001, Week 2
November 2001, Week 1
October 2001, Week 5
October 2001, Week 4
October 2001, Week 3
October 2001, Week 2
October 2001, Week 1
September 2001, Week 5
September 2001, Week 4
September 2001, Week 3
September 2001, Week 2
September 2001, Week 1
August 2001, Week 5
August 2001, Week 4
August 2001, Week 3
August 2001, Week 2
August 2001, Week 1
July 2001, Week 5
July 2001, Week 4
July 2001, Week 3
July 2001, Week 2
July 2001, Week 1
June 2001, Week 5
June 2001, Week 4
June 2001, Week 3
June 2001, Week 2
June 2001, Week 1
May 2001, Week 5
May 2001, Week 4
May 2001, Week 3
May 2001, Week 2
May 2001, Week 1
April 2001, Week 5
April 2001, Week 4
April 2001, Week 3
April 2001, Week 2
April 2001, Week 1
March 2001, Week 5
March 2001, Week 4
March 2001, Week 3
March 2001, Week 2
March 2001, Week 1
February 2001, Week 4
February 2001, Week 3
February 2001, Week 2
February 2001, Week 1
January 2001, Week 5
January 2001, Week 4
January 2001, Week 3
January 2001, Week 2
January 2001, Week 1
December 2000, Week 5
December 2000, Week 4
December 2000, Week 3
December 2000, Week 2
December 2000, Week 1
November 2000, Week 5
November 2000, Week 4
November 2000, Week 3
November 2000, Week 2
November 2000, Week 1
October 2000, Week 5
October 2000, Week 4
October 2000, Week 3
October 2000, Week 2
October 2000, Week 1
September 2000, Week 5
September 2000, Week 4
September 2000, Week 3
September 2000, Week 2
September 2000, Week 1
August 2000, Week 5
August 2000, Week 4
August 2000, Week 3
August 2000, Week 2
August 2000, Week 1
July 2000, Week 5
July 2000, Week 4
July 2000, Week 3
July 2000, Week 2
July 2000, Week 1
June 2000, Week 5
June 2000, Week 4
June 2000, Week 3
June 2000, Week 2
June 2000, Week 1
May 2000, Week 5
May 2000, Week 4
May 2000, Week 3
May 2000, Week 2
May 2000, Week 1
April 2000, Week 5
April 2000, Week 4
April 2000, Week 3
April 2000, Week 2
April 2000, Week 1
March 2000, Week 5
March 2000, Week 4
March 2000, Week 3
March 2000, Week 2
March 2000, Week 1
February 2000, Week 5
February 2000, Week 4
February 2000, Week 3
February 2000, Week 2
February 2000, Week 1
January 2000, Week 5
January 2000, Week 4
January 2000, Week 3
January 2000, Week 2
January 2000, Week 1
December 1999, Week 5
December 1999, Week 4
December 1999, Week 3
December 1999, Week 2
December 1999, Week 1
November 1999, Week 5
November 1999, Week 4
November 1999, Week 3
November 1999, Week 2
November 1999, Week 1
October 1999, Week 5
October 1999, Week 4
October 1999, Week 3
October 1999, Week 2
October 1999, Week 1
September 1999, Week 5
September 1999, Week 4
September 1999, Week 3
September 1999, Week 2
September 1999, Week 1
August 1999, Week 5
August 1999, Week 4
August 1999, Week 3
August 1999, Week 2
August 1999, Week 1
July 1999, Week 5
July 1999, Week 4
July 1999, Week 3
July 1999, Week 2
July 1999, Week 1
June 1999, Week 5
June 1999, Week 4
June 1999, Week 3
June 1999, Week 2
June 1999, Week 1
May 1999, Week 5
May 1999, Week 4
May 1999, Week 3
May 1999, Week 2
May 1999, Week 1
April 1999, Week 5
April 1999, Week 4
April 1999, Week 3
April 1999, Week 2
April 1999, Week 1
March 1999, Week 5
March 1999, Week 4
March 1999, Week 3
March 1999, Week 2
March 1999, Week 1
February 1999, Week 4
February 1999, Week 3
February 1999, Week 2
February 1999, Week 1
January 1999, Week 5
January 1999, Week 4
January 1999, Week 3
January 1999, Week 2
January 1999, Week 1
December 1998, Week 5
December 1998, Week 4
December 1998, Week 3
December 1998, Week 2
December 1998, Week 1
November 1998, Week 5
November 1998, Week 4
November 1998, Week 3
November 1998, Week 2
November 1998, Week 1
October 1998, Week 5
October 1998, Week 4
October 1998, Week 3
October 1998, Week 2
October 1998, Week 1
September 1998, Week 5
September 1998, Week 4
September 1998, Week 3
September 1998, Week 2
September 1998, Week 1
August 1998, Week 5
August 1998, Week 4
August 1998, Week 3
August 1998, Week 2
August 1998, Week 1
July 1998, Week 5
July 1998, Week 4
July 1998, Week 3
July 1998, Week 2
July 1998, Week 1
June 1998, Week 5
June 1998, Week 4
June 1998, Week 3
June 1998, Week 2
June 1998, Week 1
May 1998, Week 5
May 1998, Week 4
May 1998, Week 3
May 1998, Week 2
May 1998, Week 1
April 1998, Week 5
April 1998, Week 4
April 1998, Week 3
April 1998, Week 2
April 1998, Week 1
March 1998, Week 5
March 1998, Week 4
March 1998, Week 3
March 1998, Week 2
March 1998, Week 1
February 1998, Week 5
February 1998, Week 4
February 1998, Week 3
February 1998, Week 2
February 1998, Week 1
January 1998, Week 5
January 1998, Week 4
January 1998, Week 3
January 1998, Week 2
January 1998, Week 1
December 1997, Week 5
December 1997, Week 4
December 1997, Week 3
December 1997, Week 2
December 1997, Week 1
November 1997, Week 5
November 1997, Week 4
November 1997, Week 3
November 1997, Week 2
November 1997, Week 1
October 1997, Week 5
October 1997, Week 4
October 1997, Week 3
October 1997, Week 2
October 1997, Week 1
September 1997, Week 5
September 1997, Week 4
September 1997, Week 3
September 1997, Week 2
September 1997, Week 1
August 1997, Week 5
August 1997, Week 4
August 1997, Week 3
August 1997, Week 2
August 1997, Week 1
July 1997, Week 5
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July 1997, Week 3
July 1997, Week 2
July 1997, Week 1
June 1997, Week 5
June 1997, Week 4
June 1997, Week 3
June 1997, Week 2
June 1997, Week 1
May 1997, Week 5
May 1997, Week 4
May 1997, Week 3
May 1997, Week 2
May 1997, Week 1
April 1997, Week 5
April 1997, Week 4
April 1997, Week 3
April 1997, Week 2
April 1997, Week 1
March 1997, Week 5
March 1997, Week 4
March 1997, Week 3
March 1997, Week 2
March 1997, Week 1
February 1997, Week 5
February 1997, Week 4
February 1997, Week 3
February 1997, Week 2
February 1997, Week 1
January 1997, Week 5
January 1997, Week 4
January 1997, Week 3
January 1997, Week 2
January 1997, Week 1
December 1996, Week 5
December 1996, Week 4
December 1996, Week 3
December 1996, Week 2
December 1996, Week 1
November 1996, Week 5
November 1996, Week 4
November 1996, Week 3
November 1996, Week 2
November 1996, Week 1
October 1996, Week 5
October 1996, Week 4
October 1996, Week 3
October 1996, Week 2
October 1996, Week 1
September 1996, Week 5
September 1996, Week 4
September 1996, Week 3
September 1996, Week 2
September 1996, Week 1
August 1996, Week 5
August 1996, Week 4
August 1996, Week 3
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August 1996, Week 1
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July 1996, Week 2
July 1996, Week 1
June 1996, Week 5
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June 1996, Week 1
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May 1996, Week 1
April 1996, Week 5
April 1996, Week 4
April 1996, Week 3
April 1996, Week 2
April 1996, Week 1
March 1996, Week 5
March 1996, Week 4
March 1996, Week 3
March 1996, Week 2
March 1996, Week 1
February 1996, Week 5
February 1996, Week 4
February 1996, Week 3
February 1996, Week 2
February 1996, Week 1
January 1996, Week 5
January 1996, Week 4
January 1996, Week 3
January 1996, Week 2
January 1996, Week 1
December 1995, Week 5
December 1995, Week 4
December 1995, Week 3
December 1995, Week 2
December 1995, Week 1
November 1995, Week 5
November 1995, Week 4
November 1995, Week 3
November 1995, Week 2
November 1995, Week 1
October 1995, Week 5
October 1995, Week 4
October 1995, Week 3
October 1995, Week 2
October 1995, Week 1
September 1995, Week 5
September 1995, Week 4
September 1995, Week 3
September 1995, Week 2
September 1995, Week 1
August 1995, Week 5
August 1995, Week 4
August 1995, Week 3
August 1995, Week 2
August 1995, Week 1
July 1995, Week 5
July 1995, Week 4
July 1995, Week 3
July 1995, Week 2
July 1995, Week 1
June 1995, Week 5
June 1995, Week 4
June 1995, Week 3
June 1995, Week 2
June 1995, Week 1
May 1995, Week 5
May 1995, Week 4
May 1995, Week 3
May 1995, Week 2
May 1995, Week 1
April 1995, Week 5
April 1995, Week 4
April 1995, Week 3
April 1995, Week 2
April 1995, Week 1
March 1995, Week 5
March 1995, Week 4
March 1995, Week 3
March 1995, Week 2
March 1995, Week 1
February 1995, Week 4
February 1995, Week 3
February 1995, Week 2
February 1995, Week 1
January 1995, Week 5
January 1995, Week 4
January 1995, Week 3
January 1995, Week 2
January 1995, Week 1
December 1994, Week 5
December 1994, Week 4
December 1994, Week 3
December 1994, Week 2
December 1994, Week 1
November 1994, Week 5
November 1994, Week 4
November 1994, Week 3
November 1994, Week 2
November 1994, Week 1
October 1994, Week 5
October 1994, Week 4
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October 1994, Week 1
September 1994, Week 5
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September 1994, Week 1
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April 1994, Week 3
April 1994, Week 2
April 1994, Week 1
March 1994, Week 5
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March 1994, Week 3
March 1994, Week 2
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February 1994, Week 4
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February 1994, Week 1
February 1994
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December 1993
November 1993

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