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PubMed2001

Pharmacology and effects of cannabis: a brief review.

BACKGROUND: Increasing prevalence of recreational cannabis use among the young population has stimulated debate on the possible effects of acute and longterm use. AIMS: To highlight recent knowledge of mechanisms of action, effects on psychomotor and cognitive performance, and health risks associated with cannabis consumption. METHOD: A brief review of recent literature on the prevalence of recreational cannabis use, the potency of modern cannabis preparations and the pharmacological actions of cannabis. RESULTS: Cannabinoids derived from herbal cannabis interact with endogenous cannabinoid systems in the body. Actions on specific brain receptors cause dose-related impairments of psychomotor performance with implications for car and train driving, aeroplane piloting and academic performance. Other constituents of cannabis smoke carry respiratory and cardiovascular health risks similar to those of tobacco smoke. CONCLUSIONS: Cannabis is not, as widely perceived, a harmless drug but poses risks to the individual and to society.

Cannabinoids↗
PubMed2001

Quantitative target values of predictors of mortality in rheumatoid arthritis as possible goals for therapeutic interventions: an alternative approach to remission or ACR20 responses?

Predictors of longterm mortality in rheumatoid arthritis (RA) include patient questionnaire measures, grip strength, walk time, physician and patient assessment of global status, joint examination abnormalities, erythrocyte sedimentation rate (ESR), and morning stiffness. In the rheumatology literature, these measures have been analyzed primarily according to mean values in groups or regression analyses, which are valuable to recognize that mortality in RA is predicted by more severe disease, but do not provide the clinician with specific goals of therapy. Goals for therapeutic intervention are often expressed either as complete remission or as statistically significant differences versus a placebo, as in a 20% or even 50% response of a measure such as the American College of Rheumatology Core Data Set. Remission may be too stringent, while statistically significant efficacy of a drug compared to placebo may not necessarily indicate effectiveness to control longterm damage. An alternative approach might be to identify possible target values for therapeutic efficacy that markers of a poor prognosis be "near normal" rather than necessarily at normal or remission levels, as has been explored in management of hypertension and diabetes. However, it remains uncertain whether the goal of therapy should be a "near normal" or entirely normal values for a clinical marker. Better control of quantitative markers that predict early mortality could provide a valuable approach to improving outcomes in RA.

Arthritis, Rheumatoid↗
PubMed2000

Effect of administration of fermented milk containing whey protein concentrate to rats and healthy men on serum lipids and blood pressure.

The effect of fermented milk supplemented with whey protein concentrate on the serum lipid level of rats was investigated. The serum total cholesterol level for the group fed fermented milk with both Lactobacillus casei TMC0409 and Streptococcus thermophilus TMC 1543 was significantly lower than that of the control group (P<0.05) in rats. Furthermore, the effect of the longterm intake of this fermented milk on the serum lipid level of twenty healthy adult men was investigated. During the 8-wk study, the volunteers consumed 200 ml of fermented milk or placebo in the morning and evening. Blood samples were drawn for analysis three times, just before taking the experimental diet, and after 4 wk and 8 wk of consumption. After 8 wk, the high density lipoprotein cholesterol level for the fermented milk group showed a significant rise after 4 wk (P<0.05), whereas that of the placebo group showed no change even after 4 wk (P>0.05). The triglyceride level for the fermented milk group lowered significantly after 4 wk (<0.05), whereas that of the placebo group showed no change even after 4 wk (P>0.05). The atherogenic index [(total cholesterol - high density lipoprotein cholesterol)/high-density lipoprotein cholesterol] for the fermented milk group decreased significantly from 4.24 to 3.52 (P<0.05). The systolic blood pressure lowered significantly by the intake of fermented milk (P<0.05) On the other hand, such effect was not observed in the placebo group (P>0.05). These results indicate potential of the development of fermented milk with multiple therapeutic effects.

Adult↗
PubMed1985

Increased life expectancy resulting from addition of L-deprenyl to Madopar treatment in Parkinson's disease: a longterm study.

In an open, uncontrolled study the longterm (9 years) effect of treatment with Madopar alone (n = 377) or in combination with l-deprenyl (selegiline, selective monoamine oxidase type B inhibitor) (n = 564) have been compared in Parkinsonian patients. In patients who lost their response to conventional Madopar therapy the addition of l-deprenyl resulted in a significant recouping of levodopa effect. The survival analysis revealed a significant increase of life expectancy in Madopar--l-deprenyl group regardless of the fact whether or not the significant demographic differences between the two groups were taken into account. Although the mechanism underlying this action of l-deprenyl is not known, the results are interpreted as indicating l-deprenyl's ability to prevent or retard the degeneration of striatal dopaminergic neurons. l-Deprenyl is the first anti-Parkinson drug having such a property. This hypothesis is not far fetched since l-deprenyl selectively prevents the degeneration of striatal dopaminergic neurons induced in animals by the illicit drug 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Since latter compound is known to cause Parkinsonism in man and primates or Parkinson-like neurochemical and pathological changes in other animals the implications of the present study involving monoamine oxidase activity and l-deprenyl are apparent.

Adult↗
PubMed1999

[Lymph node positive prostate carcinoma. A case for radiotherapy].

The role of radiotherapy of the pelvic lymphatic pathways in patients with node positive prostate cancer remains uncertain. Interpretation of the few prospective studies (RTOG 75-06 and 77-06) is hampered by severe flaws in the study design. Extension of the radiation to the paraaortal region shows no advantage over radiation of the pelvic lymphatics alone and is not warranted. Data on longterm side-effects are only available from older studies with outdated radiation techniques. According to more recent studies short term side effects are considerably higher with radiation of the pelvic lymphatics when compared with radiation of the prostate alone. In summary radiation of the lymphatic pathways in lymph node positive prostate cancer cannot currently be considered as standard treatment and should be carried out within clinical studies.

Clinical Trials as Topic↗
PubMed2000

Genetic modification of haematopoietic cells for combined resistance to podophyllotoxins, other agents covered by MDR1-mediated efflux activity and nitrosoureas.

Genetic transfer and expression of drug-resistance functions into haematopoietic stem and progenitor cells is a promising means to overcome both the acute and longterm side-effects of cytotoxic drugs in bone marrow. Here, we describe a functional analysis of a retroviral vector that co-expresses human cDNAs for multidrug resistance 1/P-glycoprotein (MDR1) and a double mutant of O(6)-alkylguanine-alkyltransferase (hATPA/GA) to high levels. The hATPA/GA protein contains two amino acid substitutions that render it resistant to compounds such as O(6)-benzylguanine that inhibit the wild-type protein which is often overexpressed in resistant tumour cells. Evidence for simultaneous drug resistance of genetically modified primary murine progenitor cells to colchicine or the podophyllotoxin etoposide, both covered by MDR1-mediated efflux activity, and the nitrosourea BCNU, which is counteracted by hATPA/GA, is presented using in vitro colony assays.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1988

Teflon injections in post-prostatectomy incontinence.

Twenty-five males with post-prostatectomy incontinence due to sphincter damage underwent transperineal or transurethral Teflon injections. The results were classified into three grades: good, moderate, and poor. Good or moderate results were obtained in 24%. No major immediate complications or longterm side-effects were observed. This intervention is associated with a minimum of discomfort for the patient and hospitalization can be limited to 48-72 hours. The results are not so good as those obtained in female incontinence, and the procedure cannot be recommended as first choice treatment in patients with post-prostatectomy incontinence, but because of the simplicity of the procedure, it is considered to be a valuable alternative in patients not suitable for prosthetic surgery.

Aged↗
PubMed1999

Cost-minimisation analysis of laparoscopic and open appendicectomy.

OBJECTIVE: To compare the direct and indirect costs of laparoscopic and open appendicectomy. DESIGN: Randomised study. SETTING: University hospital, Sweden. MAIN OUTCOME MEASURES: Total costs for a defined period of time for each option. RESULTS: 102 patients were randomised and 99 were included in the final analysis. All patients had completely recovered within two months of operation. Disposable extra material used for the laparoscopic operation and longer operating time raised its median cost by SEK 912 and 1785, respectively. The mean duration of hospital stay, period off work (indirect costs), and time to complete recovery did not differ between the groups. CONCLUSION: Laparoscopic appendicectomy has higher direct costs than open operation and is not as cost-effective when the longterm outcome is the same in both groups.

Acute Disease↗
PubMed1987

Dose related coronary and systemic haemodynamic effects of intravenous bepridil in patients with coronary artery disease.

The acute coronary and systemic haemodynamic effects of intravenous bepridil were investigated in 27 patients with coronary artery disease; 13 (group 1) received 2 mg kg-1 and 14 (group 2) 4 mg kg-1 over 5 min. An immediate systemic and coronary vasodilation occurred in both groups during and immediately after the infusion. Changes were dose-related with a maximal decrease in left ventricular (LV) systolic pressure of 11% (group 1) and 18% (group 2), in mean aortic pressure of 11% (group 1) and 19% (group 2), and in coronary resistance of 23% (group 1) and 41% (group 2). Coronary flow increased by 17% (group 1) and 47% (group 2) (all changes significantly different from control (C) values and between groups). Cardiac output, measured immediately after bepridil, was unaltered, although in group 2 stroke volume index increased (14%) and systemic resistance decreased (16%), both P less than 0.05 vs C. In group 2, heart rate (HR) and contractility initially increased (8% and 10%, respectively, P less than 0.05 vs C), secondary to the greater fall in afterload, followed by a significant reduction at 5 and 10 min after bepridil (9% and 10%, respectively), accompanied by a 36% increase in LV enddiastolic pressure (P less than 0.05 vs C). No such changes were observed in group 1, apart from a simultaneous decrease in HR (9%, P less than 0.05 vs C). Thus, in humans, a dose-related, biphasic haemodynamic pattern is observed with intravenous bepridil, consisting of an acute, short-lasting vasodilation, followed by late negative chronotropic and inotropic effects, which, with longterm bepridil administration, may be beneficial during myocardial ischaemic.

Adult↗
PubMed1997

Finishing the bridge to diversity.

While much progress has been made to diversify the medical workforce in regard to gender, there is a long way to go with regard to race and ethnicity. The author emphasizes that seeking diversity in the medical professions is imperative to achieve just and equitable access to rewarding careers, improved access to health care for the under-served, culturally competent care (which includes the issue of patients' satisfaction with their care), comprehensive research agenda targeted to the problems of all areas of the population, and use of the rich and diverse pool of the nation's talent to better manage the health care system. In the 1960s the civil rights movement and civil unrest woke up the nation's institutions to the need for affirmative action initiatives, and academic medicine was one of the first to respond: there was a dramatic rise in the percentage of underrepresented minority medical school matriculants. But in the mid-1970s, this trend stalled. To state it again, the AAMC in 1991 created Project 3000 by 2000 as a longterm strategy to effect small scale educational reform in the K-12 schools and colleges that are responsible for the academic preparation of potential underrespresented-minority (URM) applicants. For a few years, the attention to URMs created by this program, and other factors, spurred a significant increase in the percentage of URM matriculants and proved the power of affirmative action. But the increase has not continued. The author maintains that this may be largely because affirmative action is being pursued with less vigor and in some cases has been stopped by law. He concludes with a vigorous defense of affirmative action and maintains that it must be used alongside more long-term solutions such as project 3000 by 2000 to achieve true diversity in the medical professions.

Academic Medical Centers↗
PubMed1980

Bomocriptine treatment of patients with acromegaly resistant to conventional therapy.

Eleven patients with active acromegaly resistant to conventional therapy were treated with bromocriptine for 15 (12--22) months by increasing the daily dose stepwise from 5 to 10--60 mg. A satisfactory response was achieved in all but one of the eight patients, in whom the mean diurnal level of serum GH was less than 50 ng/ml, whereas patients with grossly elevated serum GH levels responded poorly. In the longterm, no overall effects on glucose tolerance or plasma insulin (IRI) levels were observed but the chemical diabetes of three patients ameliorated in two. On the other hand, a dose-dependent acute suppressive effect of bromocriptine on plasma IRI response to oral glucose was observed, suggesting a direct effect of bromocriptine on the release of insulin from beta cells. Bromocriptine seems to be a good alternative in the treatment of patients with acromegaly who have not responded to conventional therapy.

Acromegaly↗
PubMed1982

Clinical use of oral verapamil in chronic and paroxysmal atrial fibrillation.

We evaluated the effectiveness of oral verapamil therapy for control of ventricular rate in digitalized patients with atrial fibrillation (AF) with three clinical problems: chronic AF with rapid rate at rest (four patients), chronic AF with accelerated rate during modest exercise (five patients), and rapid rates during paroxysmal AF (four patients). Patients in the first two categories were evaluated both by open-label dosage titration and by a randomized, double-blind, cross-over protocol. In chronic AF with rapid rate of rest, there was a significant reduction in resting heart rate (from 125 +/- 7 to 87 +/- 14, P less than 0.01) and in peak exercise heart rate (from 162 +/- 33 to 126 +/- 25, P less than 0.01). In chronic AF with rapid rate during exercise, there was also a significant decrease in resting heart rate (from 90 +/- 7 to 66 +/- 4, P less than 0.01) and in peak exercise heart rate (from 126 +/- 19 to 101 +/- 15, P less than 0.01). These effects continued during longterm follow-up of one to 12 months (mean seven months). In patients with paroxysmal AF, verapamil slowed the ventricular response from 16- +/- 24 to 72 +/- 4 P less than 0.01) with only some amelioration of symptoms. Therapy was well tolerated despite a high prevalence (seven of 13 patients) of radiographic cardiomegaly (cardiothoracic ratio greater than 0.55). We conclude that verapamil is a safe and useful drug for control of ventricular rate in digitalized patients with chronic and paroxysmal AF.

Administration, Oral↗
PubMed2006

Prevention effect of orally active heparin derivative on deep vein thrombosis.

The use of heparin as the most potent anticoagulant for the prevention of deep vein thrombosis and pulmonary embolism is nevertheless limited, because it is available to patients only by parenteral administration. Toward overcoming this limitation in the use of heparin, we have previously developed an orally active heparin-deoxycholic acid conjugate (LMWH-DOCA) in 10% DMSO formulation. The present study evaluates the anti-thrombogenic effect of this orally active LMWH-DOCA using a venous thrombosis animal model with Sprague-Dawley rats. When 5 mg/kg of LMWH-DOCA was orally administered in rats, the maximum anti-FXa activity in plasma was 0.35 +/- 0.02, and anti-FXa activity in plasma was maintained above 0.1 IU/ml [the minimum effective anti-FXa activity for the prevention of deep venous thrombosis (DVT) and pulmonary embolism (PE)] for five hours. LMWH-DOCA (5 mg/kg, 430 IU/kg) that was orally administered reduced the thrombus formation by 56.3 +/- 19.8%;on the other hand, subcutaneously administered enoxaparin (100 IU/kg) reduced the thrombus formation by 36.4 +/- 14.5%. Also, LMWH-DOCA was effectively neutralized by protamine that was used as an antidote. Therefore, orally active LMWH-DOCA could be proposed as a new drug that is effective for the longterm prevention of DVT and PE.

Administration, Oral↗
PubMedDate not supplied

[Discontinuation of neuroleptic treatment in patients with schizophrenia].

Neuroleptic maintenance treatment in schizophrenia is a conflicting issue. There is no reliable criteria to identify patients for which neuroleptic withdrawal can be experienced. However, treatment discontinuation, whose risks can be limited, must be attempted for reasons such as the patient's wellbeing, longterm side-effects prevention and patient-doctor relationship management. Anyway, it can lead to more specific indications for drug maintenance.

Antipsychotic Agents↗
PubMed1977

Surgical management of epilepsy.

Therapy with anticonvulsant drugs reduces the frequency and severity of seizures in many but not all epileptic patients. Unfortunately, in a significant number control remains poor even when maximal doses of multiple anticonvulsant drugs are given. Some of these patients are candidates for surgical treatment of epilepsy. The operative management of convulsive disorders is a well-established technique and is available in some centers. In selected cases, such operations are both safe and effective, with good longterm improvement or complete control in 76 percent of patients. We have summarized the 24-year experience with surgical operation for epilepsy at the University of Washington Medical Center.

Adolescent↗
PubMed1997

Systemic lupus erythematosus: demographics, prognosis, and outcome.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disorder with an annual incidence of 50 to 70/million and a prevalence of 500/million population. The highest incidence is observed in women aged 20 to 40 years. The clinical manifestations of SLE are remarkably heterogeneous. Major organ system involvement may occur in the heart, lungs, kidneys, and central nervous system and is responsible for most of the mortality and morbidity caused by the disease. Complications of drug treatment, in particular corticosteroid side effects, contribute to longterm morbidity. The major causes of death are directly related to the disease and include acute vascular neurologic events, renal failure, cardiovascular or pulmonary involvement, infection, and coronary artery disease.

Adolescent↗
PubMed2002

Disease modifying antirheumatic drugs in early rheumatoid arthritis: a longterm observational study.

OBJECTIVE: To investigate the effectiveness, toxicity, and drug survival in an observational longterm study of patients with early rheumatoid arthritis (RA). METHODS: Four hundred twenty-eight patients with early RA were investigated between January 1987 and December 1995. All patients had a disease duration of less than one year and had not been previously treated with any disease modifying antirheumatic drug (DMARD). The following drugs were introduced at the doses specified: hydroxychloroquine (HCQ) (200-400 mg/day), D-penicillamine (D-Pen) (500 mg/day), sulfasalazine (SSZ) (2-3 g/day), auranofin (6 mg/day), intramuscular gold (IM gold, 50 mg/week), methotrexate (MTX) (0.15 mg/kg/week, per os), cyclosporin A (CSA) (3 mg/kg/day), azathioprine (AZA) (2-3 mg/kg/day), cyclophosphamide (CYC) (1-2 mg/kg/day). RESULTS: Three hundred eighty-three patients were treated with one DMARD for at least 6 months. Sixty-five percent of patients were seropositive. The disease duration was 9.2 (3.1) months and the followup period of 12.7 (4.8) years, ranging from 7 months to 13 years. The drugs of first choice were: D-Pen (32%), HCQ (30%), MTX (21%), CSA (8%), and IM gold (7%). After the 2nd, 3rd, and 4th prescriptions, MTX was the most popular drug (27%), while D-Pen and HCQ were prescribed less frequently. The longest drug survival was seen in MTX treated patients, followed by CSA, without significant differences between them. D-Pen, HCQ, and IM gold had the largest dropout rate. The main causes for drug discontinuation were drug inefficacy (HCQ), followed by adverse drug reactions (D-Pen). CONCLUSION: It appears that MTX has the longest survival time, with CSA following in second place. The main reasons for discontinuation of treatment were drug inefficacy, followed by adverse drug reactions.

Antirheumatic Agents↗