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PubMed2004

Fulvestrant: a review of its use in hormone receptor-positive metastatic breast cancer in postmenopausal women with disease progression following antiestrogen therapy.

Fulvestrant (Faslodex) is a novel estrogen receptor (ER) antagonist that competitively binds to the ER with a much greater affinity than that of tamoxifen. The downregulation of cellular levels of the ER protein results in complete abrogation of estrogen-sensitive gene transcription. This distinct mechanism of action ensures a lack of cross resistance with other hormonal agents and, in contrast to tamoxifen, fulvestrant has no known estrogen-agonist effects. Fulvestrant is administered via monthly intramuscular injections (250mg) and is recommended for the treatment of hormone receptor-positive metastatic breast cancer in postmenopausal women with disease progression following antiestrogen therapy. The efficacy of fulvestrant was similar to that of the aromatase inhibitor anastrozole (1 mg/day) in two, well designed studies in postmenopausal women with locally advanced or metastatic breast cancer that had progressed during prior antiestrogen therapy. Time to disease progression (primary endpoint) and treatment failure, rates of objective response and clinical benefit, overall survival and quality of life were similar in patients treated with fulvestrant or anastrozole. In retrospective noninferiority analyses, fulvestrant was at least as effective as anastrozole in all randomised patients, and in those with or without visceral metastases. Fulvestrant is generally well tolerated and was tolerated as well as anastrozole in clinical trials. Treatment-related adverse events were mostly mild to moderate and led to treatment withdrawal in about 1% of patients who received fulvestrant or anastrozole. The main adverse effects associated with therapy are nausea, asthenia, pain, vasodilation and headache.In conclusion, monthly intramuscular injections of fulvestrant are at least as effective and as well tolerated as oral anastrozole once daily in the treatment of postmenopausal women with advanced breast cancer that has progressed on prior antiestrogen therapy. Because of a different mode of action to that of other hormonal agents, fulvestrant is effective in the treatment of tamoxifen-resistant disease and, unlike tamoxifen, has no known estrogen agonist effects. Thus, fulvestrant provides an effective and well tolerated option for the treatment of hormone receptor-positive metastatic breast cancer in postmenopausal women with disease progression following antiestrogen therapy.

Anastrozole↗
PubMed2004

Aprepitant: a review of its use in the prevention of chemotherapy-induced nausea and vomiting.

Aprepitant (Emend) is the first commercially available drug from a new class of agents, the neurokinin NK(1) receptor antagonists. Oral aprepitant, in combination with other agents, is indicated for the prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV) associated with highly emetogenic chemotherapy in adults. In three randomised, double-blind, placebo-controlled trials comparing aprepitant (125 mg day 1, 80mg once daily on days 2 and 3 or 2-5) plus standard therapy (intravenous ondansetron and oral dexamethasone) with standard therapy plus placebo, overall complete responses (primary endpoint, defined as no emesis and no rescue therapy) were seen in significantly more patients in the aprepitant arms (63-73% versus 43-52%, p < 0.01 for all comparisons). Complete responses and complete protection during the acute and delayed phase, and overall complete protection were also observed in significantly more patients in the aprepitant arms. The difference between treatment groups was more marked in the overall and delayed phases than in the acute phase. The antiemetic efficacy of aprepitant plus standard therapy in the prevention of CINV was maintained for up to six cycles of chemotherapy. Where assessed, more patients in the aprepitant plus standard therapy arms than the standard therapy plus placebo arms reported no impact of CINV on daily life, as assessed by the Functional Living Index-Emesis. Aprepitant is generally well tolerated. The most common adverse events in randomised trials were asthenia or fatigue. Other adverse events experienced by aprepitant recipients include anorexia, constipation, diarrhoea, nausea (after day 5 of the study) and hiccups. In addition to being a substrate for cytochrome P450 (CYP) 3A4, aprepitant is also a moderate inhibitor and inducer of this isoenzyme as well as an inducer of CYP2C9. Thus, aprepitant has the potential to interact with other agents metabolised by hepatic CYP isoenzymes. In one trial, there was a higher incidence of serious infection or febrile neutropenia in the aprepitant plus standard therapy arm than the standard therapy plus placebo arm; this was attributed to a pharmacokinetic interaction between aprepitant and dexamethasone. In subsequent trials, a modified dexamethasone regimen was used. In conclusion, when added to standard therapy (a serotonin 5-HT(3) receptor antagonist and a corticosteroid), aprepitant is effective and generally well tolerated in the prevention of CINV associated with highly emetogenic chemotherapy in adults. Despite marked advances in the prevention of CINV, standard therapy does not protect all patients. The addition of aprepitant to standard therapy provides an advance in the prevention of both acute and delayed CINV in adults with cancer.

Animals↗
PubMed1997

Terazosin. A pharmacoeconomic evaluation of its use in benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is a common disorder in elderly men which carries a substantial economic burden. Urinary symptoms associated with moderate to severe disease can significantly interfere with daily activities and reduce quality of life. Obstruction of urine flow in men with BPH can result from nonmalignant enlargement of the prostate gland (static component of BPH) and from alpha 1 receptor-mediated increased smooth muscle tone of the bladder neck and prostate (dynamic component of BPH). Transurethral resection of the prostate (TURP) is generally very effective and has traditionally been the standard treatment for men with moderate to severe BPH. However, response to therapy with TURP is not universal and the procedure is associated with a number of potential complications. Moreover, many men prefer to avoid or are not suitable candidates for this invasive procedure. Thus, there is an increasing role for less invasive treatment, including drug therapy, in men with moderate to severe BPH. Terazosin is an alpha 1 receptor antagonist which has been shown in placebo-controlled trials to significantly improve American Urology Association (AUA) symptom and quality-of-life scores and symptom problem index ('bother' score), as well as increase peak urinary flow rate, in men with BPH. In a recent large randomised US trial, treatment for 1 year with terazosin titrated to 10 mg/day improved mean AUA symptom score and peak urinary flow rate to a significantly greater extent than finasteride 5 mg/day in men with moderate to severe BPH. The most frequently reported adverse events associated with terazosin include dizziness, asthenia, postural hypotension, somnolence, headache, peripheral oedema, nasal congestion/rhinitis and syncope. Approximately 5% of men with BPH discontinue terazosin because of adverse events. Results of an economic evaluation of terazosin, in which both clinical and economic data were collected prospectively in a randomised placebo-controlled study design, showed similar total direct treatment costs per 1000 patients associated with 1 year of therapy with terazosin ($US3.57 million) and placebo ($US3.78 million) in men with moderate to severe BPH (1992 dollars). The analysis, which was conducted from the perspective of a managed care organisation in the US, demonstrated that the lower medication costs in the placebo group relative to the terazosin group were offset by increased inpatient care costs. Thus, terazosin (titrated to response up to a maximum of 10 mg/day) was significantly more effective than placebo in improving disease-specific symptoms and quality of life, but at a similar overall cost to placebo. Another economic analysis, also conducted from a third-party payer perspective in the US, modelled direct treatment costs associated with terazosin, finasteride and TURP during the first 2 years after initiating therapy in men with moderate to severe BPH. Results of the study favoured terazosin; the private insurance cost per patient undergoing primary treatment with TURP was $US6411, compared with $US2860 with finasteride (45% of the cost of TURP) and $US2422 with terazosin (38% of the cost of TURP). Medicare costs were lower for all 3 treatment groups but the relative comparisons were similar; corresponding costs per patient were $US3874, $US2161 and $US1820 (1992 dollars). A companion break-even cost analysis used a hypothetical cohort of men with BPH starting treatment at age 67 years. Private insurance costs associated with terazosin remained lower then those associated with TURP for approximately 15 years (the corresponding break-even point was 10 years for finasteride vs TRUP). Medicare costs associated with terazosin would not exceed those of TURP for approximately 7 years (5.5 years for finasteride vs TURP). In conclusion, a limited number of detailed pharmacoeconomic analysis of terazosin have been conducted to date, although it has not been compared with other a1 receptor antagonists.

Adrenergic alpha-Antagonists↗
PubMed2001

Pharmacodynamic-tolerability relationships of cholinesterase inhibitors for Alzheimer's disease.

According to the cholinergic hypothesis, the impairment of cognitive function and the behavioural disturbances that affect patients with Alzheimer's disease are mainly due to cortical deficiencies in cholinergic transmission. Numerous cholinesterase inhibitors have been investigated for treatment of this disease, the rationale being to support the cholinergic system by blocking the degradation of acetylcholine released from presynaptic neurons. These drugs can be classified as reversible (tacrine, donepezil and galantamine), pseudo-reversible (physostigmine, eptastigmine and rivastigmine) or irreversible (metrifonate) enzyme inhibitors. This article reviews efficacy and tolerability results from 6-month placebo-controlled studies of 7 cholinesterase inhibitors: tacrine (80 to 160 mg/day), donepezil (5 to 10 mg/day), rivastigmine (1 to 12 mg/day), metrifonate (30 to 80 mg/day), eptastigmine (30 to 60 mg/day), physostigmine (30 to 36 mg/day) and galantamine (8 to 32 mg/day). All these agents have demonstrated a statistically significant, although modest, effect versus placebo on the cognitive and global performance of patients with Alzheimer's disease. Dramatic clinical response has been seen in only 3 to 5% of patients. There are no major differences in terms of efficacy between the different drugs. The mean difference between drug and placebo effects on standardised psychometric scales is about 2 to 4 points on the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog; a 70-point cognitive scale) and 0.2 to 0.5 points on the Clinician's Interview-Based Impression of Change with Caregiver Input (CIBIC-Plus; a 7-point global scale), or 5 to 14% of the average value of the scales. The most common adverse effects observed after administration of cholinesterase inhibitors are nausea, vomiting, diarrhoea, dizziness, asthenia and anorexia, all symptoms linked to cholinergic overstimulation. These effects are dose related and largely depend on the degree of cholinesterase inhibition. Also important is the rate of onset of cholinesterase inhibition, which depends on the kinetics of enzyme inhibition, the presence and rate of titration, and the pharmacodynamic peak-to-trough fluctuations. A model predicting the incidence of nausea based on acetylcholinesterase inhibition and the half-life of acetylcholinesterase recovery is proposed. In conclusion, cholinesterase inhibitors are the only pharmacological agents proved to be effective for the treatment of Alzheimer's disease in large, long term, double-blind, placebo-controlled trials. While the efficacy of different cholinesterase inhibitors is similar, their tolerability profiles differ. For example, the incidence of nausea (in excess of that seen with placebo) at cognitively effective dosages ranges from 1% with eptastigmine 60 mg/day to 53% with physostigmine 30 mg/day. Differences in tolerability profile may be due to the extent of peripheral acetylcholinesterase inhibition needed to reach clinical efficacy. Other contributing pharmacodynamic factors are the rate of onset of and fluctuations in acetylcholinesterase inhibition at steady state.

Alzheimer Disease↗
PubMed2002

Spotlight on paroxetine in psychiatric disorders in adults.

Paroxetine is a selective serotonin reuptake inhibitor (SSRI), with antidepressant and anxiolytic activity. In 6- to 24-week well designed trials, oral paroxetine 10 to 50 mg/day was significantly more effective than placebo, at least as effective as tricyclic antidepressants (TCAs) and as effective as other SSRIs and other antidepressants in the treatment of major depressive disorder. Relapse or recurrence over 1 year after the initial response was significantly lower with paroxetine 10 to 50 mg/day than with placebo and similar to that with imipramine 50 to 275 mg/day. The efficacy of paroxetine 10 to 40 mg/day was similar to that of TCAs and fluoxetine 20 to 60 mg/day in 6- to 12-week trials in patients aged > or = 60 years with major depression. Paroxetine 10 to 40 mg/day improved depressive symptoms to an extent similar to that of TCAs in patients with comorbid illness, and was more effective than placebo in the treatment of dysthymia and minor depression. Paroxetine 20 to 60 mg/day was more effective than placebo after 8 to 12 weeks' treatment of obsessive-compulsive disorder (OCD), panic disorder, social anxiety disorder (social phobia), generalised anxiety disorder (GAD) and post-traumatic stress disorder (PTSD). Improvement was maintained or relapse was prevented for 24 weeks to 1 year in patients with OCD, panic disorder, social anxiety disorder or GAD. The efficacy of paroxetine was similar to that of other SSRIs in patients with OCD and panic disorder and similar to that of imipramine but greater than that of 2'chlordesmethyldiazepam in patients with GAD. Paroxetine is generally well tolerated in adults, elderly individuals and patients with comorbid illness, with a tolerability profile similar to that of other SSRIs. The most common adverse events with paroxetine were nausea, sexual dysfunction, somnolence, asthenia, headache, constipation, dizziness, sweating, tremor and decreased appetite. In conclusion, paroxetine, in common with other SSRIs, is generally better tolerated than TCAs and is a first-line treatment option for major depressive disorder, dysthymia or minor depression. Like other SSRIs, paroxetine is also an appropriate first-line therapy for OCD, panic disorder, social anxiety disorder, GAD and PTSD. Notably, paroxetine is the only SSRI currently approved for the treatment of social anxiety disorder and GAD, which makes it the only drug of its class indicated for all five anxiety disorders in addition to major depressive disorder. Thus, given the high degree of psychiatric comorbidity of depression and anxiety, paroxetine is an important first-line option for the treatment of major depressive disorder, OCD, panic disorder, social anxiety disorder, GAD and PTSD.

Adult↗
PubMed2004

Interferon-beta-1b: a review of its use in relapsing-remitting and secondary progressive multiple sclerosis.

Interferon-beta-1b (Betaseron, Betaferon) is a non-glycosylated recombinant human interferon-beta approved for high-frequency, subcutaneous (SC) administration in the treatment of multiple sclerosis (MS). Its mechanism of action is unknown, but may involve modulation of the autoimmune pathogenic processes of MS. In a randomised, double-blind trial in patients with relapsing-remitting MS (RRMS), SC interferon-beta-1b 250 micro g (8 million International Units [MIU]) every other day reduced the annual relapse rate and increased the proportion of relapse-free patients compared with placebo. It also reduced relapse severity, hospitalisations, and disease activity assessed by magnetic resonance imaging (MRI), and increased the time to first relapse. Progression of disability showed a trend towards reduction relative to placebo and baseline, but did not reach statistical significance. SC interferon-beta-1b 250 micro g every other day was shown in a randomised trial to be superior to intramuscular (IM) interferon-beta-1a 30 micro g (6 MIU) once weekly with respect to reductions in relapse-related parameters, disability progression and MRI-assessed disease activity. In patients with secondary progressive MS (SPMS), SC interferon-beta-1b 250 micro g every other day slowed progression of the disease relative to placebo in one randomised, double-blind trial, but not in another. In both studies, interferon-beta-1b 250 micro g recipients had fewer relapses and less MRI-assessed disease activity than placebo recipients. The difference in primary outcome may reflect differences in patient entry criteria. Interferon-beta-1b is generally well tolerated and the common adverse events (e.g. injection site reactions, asthenia and an influenza-like symptom complex) are clinically manageable. In a randomised trial, the tolerability of SC interferon-beta-1b 250 micro g every other day was generally similar to that of IM interferon-beta-1a 30 micro g once weekly, except for higher incidences of injection site reactions and neutralising anti-interferon-beta antibodies with SC interferon-beta-1b. In conclusion, SC interferon-beta-1b 250 micro g every other day reduces the frequency and severity of relapses and MRI measures of disease activity and may delay the progression of disability in RRMS. The drug appeared to be more effective than, and as well tolerated as, IM interferon-beta-1a 30 micro g once weekly. Interferon-beta-1b also has positive effects on relapse rates and disease activity in patients with SPMS, although its effects on disease progression remain uncertain. The drug is generally well tolerated, and the common adverse events are clinically manageable. Thus, interferon-beta-1b is a valuable first-line therapy for patients with RRMS and a potentially useful option in those with SPMS.

Age Factors↗
PubMed2001

Radioimmunotherapy: potential as a therapeutic strategy in non-Hodgkin's lymphoma.

Lymphomas are the fifth most common malignancy in the United States and are increasing in incidence. Despite being among the most responsive malignancies to radiation and chemotherapy, the majority of patients relapse or have progressive disease. Monoclonal antibodies (MAbs) directed at cell-specific surface antigens have been useful in the diagnosis of lymphomas and, more recently, the therapeutic mouse-human chimeric MAb rituximab has demonstrated effectiveness in B cell lymphomas. Conjugating MAbs to radionuclides is a strategy for improving the efficacy of MAb lymphoma therapy by delivering radiation in close proximity to the tumour (radioimmunotherapy or RIT). In addition, the low dose rate of the delivered radiation may exert a greater antitumour activity than an equivalent dose of conventional external beam radiation. The antigenic targets for MAb therapy have included CD20, CD22, HLA-DR, and B cell idiotype. Radionuclides that have been used include iodine-131, yttrium-90, and copper-67; there are relative merits and disadvantages to each source of radiation. Clinical studies to date have focused on relapsed and refractory patients with both indolent and aggressive lymphomas, although more recent studies have included previously untreated patients with indolent lymphoma. Radioimmunoconjugate has been delivered as either single or multiple doses. Response rates have varied widely, dependent on the patient population and the response criteria. Of note, complete responses can be achieved in this typically refractory patient group. Toxicities have generally consisted of mild infusion-related nausea, fever, chills, and asthenia. Neutropenia and thrombocytopenia are the dose-limiting toxicities and have prompted the incorporation of autologous stem cell support as a means of achieving dose escalation. To date, RIT has been delivered to highly selected patients in relatively few centres with requisite equipment and specialised personnel. In addition to these requirements, cost is likely to be a barrier to widespread use. The combination of RIT with chemotherapy at conventional or high dose, or with biological agents is a fertile area for investigation. The potential of RIT in the treatment for lymphomas will be defined only by well designed comparative prospective clinical studies.

Animals↗
PubMed2004

Spotlight on Interferon-beta-1b in relapsing-remitting and secondary progressive multiple sclerosis.

Interferon-beta-1b (Betaseron, Betaferon) is a non-glycosylated recombinant human interferon-beta approved for high-frequency, subcutaneous (SC) administration in the treatment of multiple sclerosis (MS). Its mechanism of action is unknown, but may involve modulation of the autoimmune pathogenic processes of MS. In a randomized, double-blind trial in patients with relapsing-remitting MS (RRMS), SC interferon-beta-1b 250 micro g (8 million International Units [MIU]) every other day reduced the annual relapse rate and increased the proportion of relapse-free patients compared with placebo. It also reduced relapse severity, hospitalizations, and disease activity assessed by magnetic resonance imaging (MRI), and increased the time to first relapse. Progression of disability showed a trend towards reduction relative to placebo and baseline, but did not reach statistical significance. SC interferon-beta-1b 250 micro g every other day was shown in a randomized trial to be superior to intramuscular (IM) interferon-beta-1a 30 micro g (6 MIU) once weekly with respect to reductions in relapse-related parameters, disability progression and MRI-assessed disease activity. In patients with secondary progressive MS (SPMS), SC interferon-beta-1b 250 micro g every other day slowed progression of the disease relative to placebo in one randomized, double-blind trial, but not in another. In both studies, interferon-beta-1b 250 micro g recipients had fewer relapses and less MRI-assessed disease activity than placebo recipients. The difference in primary outcome may reflect differences in patient entry criteria. Interferon-beta-1b is generally well tolerated and the common adverse events (e.g. injection site reactions, asthenia and an influenza-like symptom complex) are clinically manageable. In a randomized trial, the tolerability of SC interferon-beta-1b 250 micro g every other day was generally similar to that of IM interferon-beta-1a 30 micro g once weekly, except for higher incidences of injection site reactions and neutralizing anti-interferon-beta antibodies with SC interferon-beta-1b. In conclusion, SC interferon-beta-1b 250 micro g every other day reduces the frequency and severity of relapses and MRI measures of disease activity and may delay the progression of disability in RRMS. The drug appeared to be more effective than, and as well tolerated as, IM interferon-beta-1a 30 micro g once weekly. Interferon-beta-1b also has positive effects on relapse rates and disease activity in patients with SPMS, although its effects on disease progression remain uncertain. The drug is generally well tolerated, and the common adverse events are clinically manageable. Thus, interferon-beta-1b is a valuable first-line therapy for patients with RRMS and a potentially useful option in those with SPMS.

Drug Administration Schedule↗
PubMedDate not supplied

Denileukin diftitox.

Denileukin diftitox is a novel interleukin-2 receptor (IL-2R)-targeted diphtheria toxin. It binds to cells expressing IL-2R and inhibits protein synthesis through internalization of the diphtheria toxin fragment. In patients with IL-2R-positive cutaneous T cell lymphoma (CTCL), the overall response rate was 23 and 36%, respectively, after denileukin diftitox 9 or 18 micrograms/kg/day for 5 days every 3 weeks and was 37% in a dose-ranging trial. Quality of life (QOL) improved significantly in patients with CTCL who responded to treatment with denileukin diftitox 9 or 18 micrograms/kg/day compared with QOL at baseline and in nonresponders. In a murine model of IL-2R-expressing malignancy, denileukin diftitox prolonged survival compared with controls. The most common adverse events reported in patients who received denileukin diftitox were hypoalbuminemia, fever/chills, acute hypersensitivity reactions, nausea/vomiting and asthenia. Vascular leak syndrome has occurred during denileukin diftitox therapy. Antibody titers to denileukin diftitox occur in most patients after treatment but the presence of antibodies does not preclude a clinical response.

Animals↗
PubMed2004

Rosuvastatin: a review of its use in the management of dyslipidemia.

Rosuvastatin (Crestor), an HMG-CoA reductase inhibitor (statin), has a favorable pharmacologic profile, including its selective uptake by hepatic cells, hydrophilic nature, and lack of metabolism by cytochrome p450 (CYP) 3A4 isoenzyme. This last property means that the potential for CYP3A4-mediated drug interactions and, as a consequence, adverse events is low in those requiring concomitant therapy with a statin and agents metabolized by CYP3A4. In a broad spectrum of adult patients with dyslipidemias, oral rosuvastatin 5-40 mg once daily effectively and rapidly improved lipid profiles in several large, randomized, mainly double-blind, multicenter trials of up to 52 weeks' duration. After 12 weeks' treatment, rosuvastatin was significantly (all p < 0.05) more effective at milligram equivalent dosages than atorvastatin, pravastatin, and simvastatin in improving the overall lipid profiles of patients with hypercholesterolemia (intent-to-treat analyses). Moreover, overall a significantly (all p < 0.001) higher proportion of patients achieved National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III low-density lipoprotein-cholesterol (LDL-C) goals with rosuvastatin 10 mg/day than with therapeutic starting dosages of these other statins after 12 weeks' treatment in pooled analyses. Rosuvastatin treatment for up to 52 weeks was generally well tolerated in patients with dyslipidemias in clinical trials. The most commonly reported treatment-related adverse events were myalgia, constipation, asthenia, abdominal pain, and nausea; these were mostly transient and mild. The incidence of proteinuria or microscopic hematuria with rosuvastatin 10 or 20 mg/day was <1% versus <1.5% with rosuvastatin 40 mg/day; these events were mostly transient and not associated with acute or progressive deterioration in renal function at recommended dosages. Importantly, very few patients experienced elevations in serum creatine phosphokinase (CPK) levels of over [corrected] 10-fold the upper limit of normal (0.2-0.4% of patients) or treatment-related myopathy (<or=0.1%) [i.e. muscle aches or weakness plus the same elevated serum CPK levels] at dosages of 5-40 mg/day. In conclusion, rosuvastatin treatment effectively and rapidly improves the lipid profile in patients with a broad spectrum of dyslipidemias. In those with hypercholesterolemia (including high-risk patients), rosuvastatin was more efficacious than and generally as well tolerated as atorvastatin, simvastatin, and pravastatin, with significantly more rosuvastatin recipients achieving their NCEP ATP III target LDL-C levels. Thus, rosuvastatin has emerged as a valuable choice for first-line treatment in the management of low- to high-risk patients requiring lipid-lowering drug therapy.

Drug Interactions↗
PubMedDate not supplied

An outbreak of acute pulmonary histoplasmosis in members of a trekking trip in Martinique, French West Indies.

BACKGROUND: Thirteen clustered cases of American histoplasmosis, a deep mycosis caused by Histoplasma capsulatum and acquired through inhalation of airborne spores was reported. Twenty-five persons traveled in Martinique, French West Indies. Thirteen underwent trekking and passed through a mountain tunnel full of bats (tunnel group). The 12 others performed canyoning and did not go through the tunnel (control group). Fifteen days after exposure, 1 patient of the tunnel group developed fever, chills, and cough. METHODS: The index case was diagnosed in the hospital, but 12 cases where initially diagnosed as prolonged influenza. All individuals were contacted and submitted to a phone questionnaire. They were asked about eventual occurrence of influenzalike symptoms, about activities practiced, and the notion of contact with bats. All were invited to have clinical examinations, chest x-ray films, and blood samplings. Serologic testing for histoplasmosis was performed by immunodiffusion. Clinical evidence of infection with H. capsulatum was obtained in all the remaining patients of the tunnel group and in none in the control group. Symptoms occurred with an acute onset in 11 to 23 days: fever and chills, severe asthenia, headaches, digestive tract involvement, and then cough, dyspnea, hepatic involvement. Pulmonary micro- or macronodules and mediastinal adenopathies were seen on radiograph and/or computed tomography scan. RESULTS: H. capsulatum serologic tests were positive in all 13 cases with presence of specific M and or H precipitins, 5 to 13 weeks after exposure, and were negative in control group. All patients were treated with itraconazole 200 mg per day during at least 2 months. Treatment was well tolerated; patients progressively recovered. Clinical and serologic follow-up was obtained for some patients at 1 and 4 years. The present study reports the first large outbreak of histoplasmosis acquired in Martinique. CONCLUSION: Histoplasmosis still occurs and is potentially serious. In patients returning from endemic areas, presenting prolonged influenzalike symptoms, clinicians should look for previous possible exposure to Histoplasma.

Acute Disease↗
PubMed1997

A double-masked placebo-controlled trial assessing effects of various doses of BTS 67,582, a novel insulinotropic agent, on fasting hyperglycemia in NIDDM patients.

OBJECTIVE: To determine the effect over a 4-week period of varying doses of BTS 67,582, a novel nonsulfonylurea insulinotropic agent, on fasting plasma glucose (FPG) levels in sulfonylurea-responsive NIDDM patients. RESEARCH DESIGN AND METHODS: This was a 12-week multicenter, double-masked, placebo-controlled trial. Patients entered a 4-week stabilization period during which they received their previously prescribed sulfonylurea. Qualified patients (FPG < or = 10 mmol/l) then entered a 4-week sulfonylurea withdrawal single-masked placebo run-in period. Qualified patients (FPG 8.9-16.7 mmol/l) were randomized to either placebo (n = 14), 50 mg b.i.d. BTS 67,582 (n = 18), 250 mg b.i.d. BTS 67,582 (n = 18), 500 mg b.i.d. BTS 67,582 (n = 15), 100 mg q.d. BTS 67,582 (n = 17), or 500 mg q.d. BTS 67,582 (n = 16). The primary efficacy variables were mean changes from baseline in FPG and fructosamine (FRUC). Additional variables included mean changes from baseline in HbA1c, fasting serum insulin (FSI), and fasting serum C-peptide. RESULTS: After 4 weeks of treatment, all BTS 67,582 dose groups showed a decrease from baseline in FPG and FRUC compared with the placebo group. The treatment groups of 250 mg b.i.d. (-3.1 +/- 0.7 mmol/l), 500 mg b.i.d. (-2.3 +/- 0.6 mmol/l), and 500 mg q.d. (-1.2 +/- 0.7 mmol/l) had statistically significant (P < 0.05) decreases in FPG compared with placebo (0.7 +/- 0.6 mmol/l). Similarly, there were statistically significant (P < 0.05) decreases from baseline in FRUC for the 250 mg b.i.d (-55 +/- 10 mumol/l), 500 mg b.i.d. (-40 +/- 12 mumol/l), and 500 mg q.d. (-13 +/- 9 mumol/l) treatment groups compared with placebo (15 +/- 11 mumol/l). Although the treatment period was only 4 weeks in duration, there were also significant differences (P < 0.05) in the HbA1c changes from baseline for the 250 mg b.i.d. (0.0 +/- 0.1%) and 500 mg b.i.d. (-0.2 +/- 0.1%) treatment groups compared with placebo (0.6 +/- 0.2%). There were no significant differences among the treatment groups in the changes from baseline for FSI or C-peptide levels. The most frequently reported side effects were headache, asthenia, infection, and thirst, and the incidence of these events as well as the incidence of study drug discontinuation was comparable in all treatment groups including placebo. CONCLUSIONS: Four weeks of treatment with BTS 67,582 at doses of 250 mg b.i.d. and 500 mg b.i.d. in NIDDM patients was effective in reducing FPG and FRUC, with significant results also seen for HbA1c. The drug was well tolerated with an incidence of discontinuations and laboratory side-effect safety profiles comparable to placebo. BTS 67,582 is a safe and effective oral treatment for NIDDM patients.

Adult↗
PubMed1995

Voice evaluation before and after laser excision vs. radiotherapy of T1A glottic carcinoma.

Quality of voice after treatment for T1A glottic squamous cell carcinoma was studied in two matched groups of males treated either with CO2 laser cordectomi (n = 18, mean age 65.2 years) or with full dose radiotherapy (n = 18, mean age 65.1 years). All patients had histologically verified invasive squamous cell carcinoma. Fifteen male patients (mean age 63.9 years) without laryngeal disorders were used as controls. Voice recordings prior to treatment, and both at 3 months and at 2 years after completed treatment were analyzed. Acoustic measures of shimmer, jitter, breathiness, harmonic-to-noise ratio and fundamental frequency (F0) average were calculated with the Soundscope program. Two plain measures were also used: time required to read a running speech voice sample, and number of breaths. Perceptual voice analysis was performed blindly by two groups of listeners, Group A (4 experienced listeners) and Group B (4 naive listeners). Group A estimated quality of voice according to a modified GRBAS score, whereas Group B estimated Grade only. We found voice quality both at 3 months and at 2 years after radiotherapy to be significantly better than after laser treatment, as assessed by the acoustic variables breathiness, jitter, F0 average, running speech voice sample reading time and number of breaths. The perceptual variables Grade (Group A and B), Breathiness, Asthenia and Strain were also significantly better after radiotherapy.

Adult↗
PubMed1995

Gender and clinical presentation in adult celiac disease.

BACKGROUND: Celiac disease may present in various forms. This study aimed to investigate whether gender affects the clinical presentation of the disease in adult celiac patients from the Mediterranean area. METHODS: This study retrospectively analyzes data collected in all adult patients with celiac disease (n = 195) seen during the past 13 years at the Gastrointestinal Unit of the Federico II University of Naples, Italy. RESULTS: In these series of patients the ratio of women to men was 3.33. Age at diagnosis was lower in women that in men (p < 0.05). Except for asthenia, all signs and symptoms were more frequent in women than in men. Hypochromic anemia was the most commonest finding in women and was 40% more frequent in women than in men (p < 0.001). Dyspepsia was twice as frequent in women as in men (p < 0.05); genital disorders were reported by 44% of women and by no men. Recent weight loss or low body mass index was the commonest finding in men. About 60% of men and women reported diarrhea; among patients without diarrhea, the prevalence of hypochromic anemia differed between sexes (p < 0.05), occurring in about 80% of women. CONCLUSION: This study shows that the clinical presentation of celiac disease is not the same in men and women. The disease is not only more frequent in women than in men but is also more severe and more rapid. The data also suggest the need to look for celiac disease in patients with unexplained hypochromic anemia.

Adult↗
PubMed1996

Subjective muscle weakness and hypotonia during clozapine treatment.

Four cases of patients who described an unpleasant subjective experience of weakness and reduced muscle tone during treatment with clozapine are presented. An exacerbation of muscular dystrophy during clozapine treatment is also described. It is hypothesized that these adverse effects are related to the muscle relaxant properties of clozapine. The differential diagnosis of sedation, fatigue, asthenia, and reduced muscle tone is discussed.

Adult↗
PubMed1990

Intrasellar mass with hypopituitarism as a manifestation of sarcoidosis. Case report.

A 45-year-old woman was admitted suffering from headache, weight loss, asthenia, pedal edema, and amenorrhea. Morphological and functional studies revealed an intrasellar mass causing hypopituitarism without diabetes insipidus. Histological examination of the tissue obtained at transsphenoidal surgery was compatible with a diagnosis of sarcoidosis. The clinical and histological features, together with the presence of cutaneous anergy and ocular lesions, led to the diagnosis of sarcoidosis. The presentation of sarcoidosis in this patient was very unusual because it was not accompanied by characteristic intrathoracic findings or by diabetes insipidus.

Female↗
PubMed2000

Osteoreflectory treatment of alcohol abstinence syndrome and craving for alcohol in patients with alcoholism.

Osteoreflexotherapy is used alone as a treatment used for alcohol abstinence syndrome and for alcohol craving by intraosseal stimulation of the processus styloideus ulnae of the patient's left and right hands as well as the processus spinosus of the seventh cervical vertebra and the manubrium sterni osteoreceptors. This is done by intraosseal injection of 0.5 to 1.0 ml of 0.9% NaCl solution during a period of 3 to 5 seconds. Craving for alcohol and depressed mood, strongly manifested Alcohol Abstinence Syndrome (AAS) symptoms before osteoreflexotherapy, were reduced in a most convenient and fast manner under the influence of two sessions of osteoreceptive stimulation. The withdrawal symptoms caused by alcohol abstinence decreased markedly during the first two hours after the first osteoreflexotherapy treatment, continued to decrease in the next 24 hours and by the time the second osteoreflexotherapy session was given, the withdrawal symptoms completely disappeared in 72 hours. The most slowly and least reduced AAS symptoms were asthenia and disturbances of postular equilibrium. Based on clinical observations, it is speculated that osteoreceptive stimulations destroy ethanol dependent functional systems and restore the neurophysiological and neuromediatorial integration of the brain in alcoholismpatients. Primarily because of these two cited factors, the patient can be freed of the craving for alcohol for several years, and he or she also does not suffer from depression.

Adult↗
PubMed2005

Colorectal cancer in geriatric patients: endoscopic diagnosis and surgical treatment.

AIM: To investigate the prevalence of colorectal cancer in geriatric patients undergoing endoscopy and to analyze their outcome. METHODS: All consecutive patients older than 80 years who underwent lower gastrointestinal endoscopy between January 1995 and December 2002 at our institution were included. Patients with endoscopic diagnosis of colorectal cancer were evaluated with respect to indication, localization and stage of cancer, therapeutic consequences, and survival. RESULTS: Colorectal cancer was diagnosed in 88 patients (6% of all endoscopies, 55 women and 33 men, mean age 85.2 years). Frequent indications were lower gastrointestinal bleeding (25%), anemia (24%) or sonographic suspicion of tumor (10%). Localization of cancer was predominantly the sigmoid colon (27%), the rectum (26%), and the ascending colon (20%). Stage Dukes A was rare (1%), but Dukes D was diagnosed in 22% of cases. Curative surgery was performed in 54 patients (61.4%), in the remaining 34 patients (38.6%) surgical treatment was not feasible due to malnutrition and asthenia or cardiopulmonary comorbidity (15 patients), distant metastases (11 patients) or refusal of operation (8 patients). Patients undergoing surgery had a very low in-hospital mortality rate (2%). Operated patients had a one-year and three-year survival rate of 88% and 49%, and the survival rates for non-operated patients amounted to 46% and 13% respectively. CONCLUSION: Nearly two-thirds of 88 geriatric patients with endoscopic diagnosis of colorectal cancer underwent successful surgery at a very low perioperative mortality rate, resulting in significantly higher survival rates. Hence, the clinical relevance of lower gastrointestinal endoscopy and oncologic surgery in geriatric patients is demonstrated.

Aged↗