drugadvisor

Solitary plasmacytoma of bone--a rare disorder with an unusual evolution.

Solitary plasmacytoma of bone--a rare disorder with an unusual evolution. A 40 year old woman presented with a spinal epidural tumour, which on histology was shown to be a plasmacytoma. At that time she had no evidence of multiple myeloma. Ten months later, she developed a second isolated plasmacytoma in the spleen, for which she underwent splenectomy. Two years after her initial presentation she had another recurrence in the liver, followed by a full-blown picture of multiple myeloma. The myeloma was progressive and resistant to all forms of chemotherapy. She finally died of a massive gastrointestinal haemorrhage. The clinical features, natural evolution and management of solitary plasmacytomas are discussed. Journal ISSN: 0032-5473 Issue: 69-808 (1993) Pages: 153-4

Studies on the antihypertensive action of L-tryptophan.
Studies on the antihypertensive action of L-tryptophan. The administration of L-tryptophan to spontaneously hypertensive rats caused a dose-related decrease in blood pressure. Maximal reductions occurred 2 hr postinjection. This effect could be attenuated by 1) coadministration of valine, an amino acid that competes with tryptophan for brain uptake; 2) pretreatment with metergoline, a serotonin receptor antagonist; and 3) pretreatment with parachlorophenylalanine, which inactivates tryptophan hydroxylase. In contrast, the effect of tryptophan on blood pressure could be enhanced by pretreatment with fluoxetine, a drug which blocks serotonin reuptake into presynaptic terminals. Taken together, these results indicate that tryptophan injection lowers blood pressure by a mechanism involving increased tryptophan uptake into brain, followed by enhanced conversion of the amino acid to serotonin (not tryptamine) and, ultimately, increased release of serotonin by brain neurons. The data thus support the notion that serotonergic neurons in the rat brain function in circuits that lower blood pressure. Journal ISSN: 0022-3565 Issue: 221-2 (1982) Pages: 329-33

Differential effects of fluoxetine and zimelidine on the uptake of 5-hydroxytryptamine and tryptamine by cortical slices and on responses of cortical neurones to stimulation of the nucleus raphe medianus.
Differential effects of fluoxetine and zimelidine on the uptake of 5-hydroxytryptamine and tryptamine by cortical slices and on responses of cortical neurones to stimulation of the nucleus raphe medianus. Intravenous administration of fluoxetine inhibited the uptake of tryptamine and 5-hydroxytryptamine by cortical slices. In contrast, zimelidine inhibited the uptake of 4-hydroxytryptamine only. In vivo, inhibitory and excitatory response of cortical neurones to stimulation of raphe medianus were potentiated by fluoxetine whereas only excitatory responses were enhanced by zimelidine. The results are consistent with the suggestion that the inhibitory effects of raphe stimulation are mediated by tryptamine and the excitatory responses by 5-hydroxytryptamine. Journal ISSN: 0014-2999 Issue: 81-4 (1982) Pages: 681-5

Intraperitoneal high-dose cisplatin and etoposide with systemic thiosulfate protection in second-line treatment of advanced ovarian cancer.
Intraperitoneal high-dose cisplatin and etoposide with systemic thiosulfate protection in second-line treatment of advanced ovarian cancer. Several randomized trials of various malignancies treated with cisplatin indicate a dose-response relationship with higher MST and longer survival achieved with high-dose compared to standard dose cisplatin regimens. Thirty-five patients with stages II-IV ovarian cancer with refractory cancer at second look or recurrent disease were treated second line with intraperitoneal (ip) combination chemotherapy of high-dose cisplatin (100-200 mg/m2) plus etoposide (350 mg/m2) in 1-6 cycles. Sodium thiosulfate was given as an intravenous antidote to cisplatin. A WBC nadir < 2.0 x 10(9)/liter was registered in 39 courses and a platelet nadir < 50 x 10(9)/liter in 3 courses. Severe nephrotoxicity was observed in 2 patients. Nonhematologic and nonrenal toxicity was mild except for vomiting and nausea and alopecia. No severe neurotoxicity was observed. A total of 127 courses were administered. Total median administered dose was 960 mg and 49 mg/m2/week. Treatment was changed in 5 (14%) patients due to severe nausea and vomiting, in 4 (11%) patients due to PAC problems, and in 2 (6%) patients due to nephrotoxicity. In 4 (11%) patients the dose was reduced due to hematologic toxicity. No toxic death was recorded. Median survival time from date of diagnosis was 21.8 (mean 37.9) months and the median progression-free survival from start of ip chemotherapy was 13.7 months. For patients with MRD < or = 2 cm the MST was 18.1 months. At the closing point of this study after a median follow-up time of 16.1 (range, 4.6-55.6) months, 7 (20%) patients were alive without evidence of progression, 4 (11%) were alive with cancer, and 23 (66%) were dead of cancer and 1 (3%) was dead of intercurrent disease. Journal ISSN: 0090-8258 Issue: 49-2 (1993) Pages: 166-71

Antiproliferative effects on human peripheral blood mononuclear cells and inhibition of in vitro immunoglobulin synthesis by Podophyllotoxin (CPH86) and by semisynthetic lignan glycosides (CPH82).
Antiproliferative effects on human peripheral blood mononuclear cells and inhibition of in vitro immunoglobulin synthesis by Podophyllotoxin (CPH86) and by semisynthetic lignan glycosides (CPH82). A mixture of natural and semisynthetic (modified) glycosides from Podophyllum emodi (Proresid) has been used for many years in the treatment of rheumatoid arthritis, but its use is hampered by gastrointestinal side effects. Highly purified podophyllotoxin (CPH86) and a preparation containing two semisynthetic podophyllotoxin glycosides (CPH82) are currently being tested in clinical trials. In this study these drugs were shown to inhibit in vitro [3H]-thymidine uptake of human peripheral blood mononuclear cells stimulated by the mitogens concanavalin A, phytohemagglutinin and pokeweed mitogen. Complete inhibition was observed with CPH86 in concentrations > or = 20 ng/ml and with CPH82 in concentrations > or = 1 microgram/ml. In vitro production of IgG, IgM and IgA by PWM-stimulated cells cultured for 7 days was unaffected by 10 ng/ml CPH86 and 100 ng/ml CPH82, but was strongly inhibited by concentrations of CPH86 at > or = 20 ng/ml and CPH82 at > or = 1 microgram/ml. In conclusion, both CPH86 and CPH82 inhibit mitogen induced lymphocyte proliferation and immunoglobulin synthesis and the results may be of help in determining optimal dose levels if related to treatment effects. Journal ISSN: 0392-856X Issue: 11-2 (1993 Mar-Apr) Pages: 179-82

Anti-inflammatory activity of H1-receptor antagonists: review of recent experimental research.

Anti-inflammatory activity of H1-receptor antagonists: review of recent experimental research. OBJECTIVE: To compare the anti-inflammatory effects of fexofenadine with other H(1)-receptor antagonists in vitro. DATA SOURCES: Published literature. STUDY SELECTION: Recent experimental studies on anti-inflammatory effects of H(1)-receptor antagonists. Databases searched: Medline, Medscape. Period covered: 1990-2003. Search terms: second-, third-generation antihistamines; sedating, nonsedating antihistamines; in vitro anti-inflammatory activity; cetirizine; ebastine; loratadine; fexofenadine; desloratadine. RESULTS: Second- and third-generation H(1)-receptor antagonists may demonstrate significant in vitro anti-inflammatory activity at concentrations considered to be clinically relevant. In some instances, higher (supraclinical) concentrations are required to achieve comparable effects. CONCLUSIONS: Experimental research suggests that second- and third-generation H(1)-receptor antagonists may achieve anti-inflammatory effects in a clinical context. Further studies are required to support this conclusion. Journal ISSN: 0300-7995 Issue: 20-1 (2004) Pages: 73-81

Amitriptyline plasma protein binding: effect of plasma pH and relevance to clinical overdose.
Amitriptyline plasma protein binding: effect of plasma pH and relevance to clinical overdose. Reversing ventricular ectopy with plasma alkalinization following acute tricyclic antidepressant overdose is a recognized mode of therapy. The mechanism responsible for this effect is unclear. Changes in plasma protein binding of free drug, effects of the sodium ion on the myocardium, and alterations of plasma concentrations of alpha-1-acid glycoprotein may all interact to alter toxicity of tricyclics in overdose. An in vitro investigation using equilibrium dialysis was designed to examine the effect of altering plasma pH on percentage of free amitriptyline at clinical overdose plasma concentrations. A 1973 report on this effect lacked adequate controls and was faulty in experimental protocol. The current investigation used plasma concentrations typically present in amitriptyline overdose, a sensitive gas liquid chromatographic assay to detect total and free drug, and adequate control of plasma pH. The results of two separate experiments demonstrated a significant decrease in percentage of free amitriptyline of 20% over a pH range of 7.0-7.4 (P less than 0.05) and 42% over a pH range of 7.4-7.8 (P less than 0.05). The rate of change in slope in both experiments was not significantly different (P less than 0.01) indicating similar effects of pH change on plasma protein binding of amitriptyline within the two groups. Journal ISSN: 0735-6757 Issue: 4-2 (1986) Pages: 121-5

Effects of combined administration of L-tryptophan and tricyclic antidepressants on alpha 2- and beta-adrenoceptors and monoamine levels in rat brain.
Effects of combined administration of L-tryptophan and tricyclic antidepressants on alpha 2- and beta-adrenoceptors and monoamine levels in rat brain. In order to test whether co-administration of a serotonin precursor with antidepressant drugs could potentiate the effects of the antidepressants on monoamines or adrenoceptors in rat brain, L-tryptophan (20 mg/kg) was administered to rats daily for 7 or 15 days, either alone or in combination with desipramine (10 mg/kg) or amitriptyline (10 mg/kg). After treatment with L-tryptophan for 7 days, increases were observed in rat hypothalamic and frontal cortex 5-hydroxy-3-indoleacetic acid levels as well as in hypothalamic dopamine and nucleus accumbens 3,4-dihydroxyphenylacetic acid levels. After 15 days, hippocampal beta-adrenoceptor density was found to be decreased. There was no evidence of potentiation of desipramine or amitriptyline action when L-tryptophan was administered in combination with the antidepressants. On the contrary, the antidepressants appeared to interact with L-tryptophan to reduce its effects. Journal ISSN: 0364-3190 Issue: 10-12 (1985) Pages: 1661-71

Randomized, double-masked comparison of olopatadine ophthalmic solution, mometasone furoate monohydrate nasal spray, and fexofenadine hydrochloride tablets using the conjunctival and nasal allergen challenge models.

Randomized, double-masked comparison of olopatadine ophthalmic solution, mometasone furoate monohydrate nasal spray, and fexofenadine hydrochloride tablets using the conjunctival and nasal allergen challenge models. BACKGROUND: It is presumed that exposure to allergens in the environment occurs through both the eyes and the nose. Allergic rhinoconjunctivitis is typically treated with a nasal spray or systemic antihistamine, neither of which may provide adequate relief of the ocular component of the disease. OBJECTIVE: This study was designed to gain a better understanding of the physiologic interaction between the conjunctival and nasal mucosa and thus help establish a profile for the most effective ocular treatment in patients whose allergies have both an ocular and a nasal component. METHODS: This was a single-center, randomized, double-masked clinical study using the conjunctival allergen challenge (CAC) and nasal allergen challenge (NAC) models. It compared the clinical signs and symptoms induced by CAC and NAC, the effects of drugs administered by 3 different routes, and the movement of fluorescein after instillation into the eye and nose (Jones test), and assessed levels of of inflammatory mediators in tears and nasal secretions. At visit l, subjects previously identified as CAC responders underwent NAC to determine the dose of allergen necessary to elicit a sufficient positive reaction. At visit 2, which took place 1 week later, subjects with a positive reaction at visit 1 were randomized to group A (CAC) or group B (NAC), and underwent challenge to confirm the allergen dose necessary to produce a positive reaction. Subjects who qualified were randomized to receive 1 of 3 treatments: olopatadine 0.1% ophthalmic solution, placebo nasal spray, and placebo tablets; mometasone furoate monohydrate 50-microg nasal spray, placebo topical solution, and placebo tablets; or fexofenadine hydrochloride 180-mg tablets, placebo topical solution, and placebo nasal spray. All study medications were administered according to their approved labeling: drops were administered twice daily in the eyes, and the nasal sprays and tablets were administered once daily. At visit 3, which took place 1 week after visit 2, subjects received study medication and 15 minutes later underwent CAC or NAC as before. The primary efficacy variables were ocular itching, ocular redness, and overall nasal symptoms (sneezing, rhino rrhea/postnasal drip, nasal pruritus, palatal pruritus, and nasal congestion) rated on standard scales. Peak nasal inspiratory flow (PNIF) was measured at each visit, and the Jones test was performed at visits 1 and 3. At baseline and after challenge at visits 2 and 3, tear and nasal lavage samples were collected from a subset of randomly selected subjects for analysis of eosinophil cationic protein and tryptase. RESULTS: Seventy-three subjects (42 women, 31 men; mean age, 45.26 years [range, 21-73 years]) were screened, and all were randomized to treatment. Two subjects did not complete the study. CAC induced clinically significant (>1 unit difference) ocular and nasal signs and symptoms, whereas NAC induced clinically significant nasal signs and symptoms only. In group A, there was a greater reduction in ocular itching with olopatadine compared with mometasone and fexofenadine at 3 minutes (P = 0.003 and P = 0.008, respectively) and 5 minutes (P = 0.007 and P = 0.013) after challenge. Although the difference was not statistically significant, overall relief of conjunctival redness (average of 3 vessel beds) was greatest in the olopatadine group, followed by fexofenadine. In group B, prevention of total nasal symptoms was significantly greater with mometasone compared with fexofenadine at 20 minutes (P = 0.006) and 30 minutes (P = 0.014) after challenge. There were no statistically significant differences between treatment groups in nasal symptom scores at any time point after CAC. There were also no significant differences in PNIF between treatment groups. Fluorescein was present in nasal secretions within 5 minutes of being instilled into the eye; no fluorescein was detected in the eye after instillation into the nose. CONCLUSIONS: In this study, exposure of the nasal mucosa to allergen resulted in allergic rhinitis, and exposure of the ocular the ocular surface to allergen resulted in conjunctivitis with a secondary effect in the nose. These results suggest movement of allergens, their mediators, and antiallergy drugs from the ocular surfaces into the nasal cavity, with no meaningful movement from the nasal cavity to the ocular surface. In this controlled model, both the systemic agent and the nasal spray failed to control ocular symptoms. The topical ophthalmic solution provided the most effective management of allergic ocular signs and symptoms, and the nasal spray was most effective for nasal symptoms. Combined use of a nasal spray and topical ophthalmic solution may provide maximal relief in patients whose allergies have both ocular and nasal components. Journal ISSN: 0149-2918 Issue: 25-8 (2003) Pages: 2245-67

[Erectile dysfunction in cardiovascular diseases]
[Erectile dysfunction in cardiovascular diseases] After the acute phase, a patient who is diagnosed with cardiac or vascular disease becomes "chronically ill". This patient will then still spend many years without symptoms or impairments. One day, a percentage of such patients will be confronted with the problem of erectile dysfunction. Various studies have demonstrated that this problem occurs with a higher frequency in patients with cardiovascular diseases, in particular when they have to be treated for hypertension, diabetes mellitus or dyslipidemia. Very rarely are stenoses or occlusions found in the arteries responsible for penile circulation. More recent data indicates that a diffuse anomaly of the vascular endothelium is present, for which erectile dysfunction is a marker. Nowadays, medical care has achieved a better degree of standardization, not only thanks to knowledge about the effects of cardiovascular medication, but also because the physician can now prescribe drugs that treat erectile dysfunction. Journal ISSN: 1013-2058 Issue: 92-20 (2003) Pages: 950-5

Comparison of the flow properties of aqueous suspension corticosteroid nasal sprays under differing sampling conditions.
Comparison of the flow properties of aqueous suspension corticosteroid nasal sprays under differing sampling conditions. Many aqueous suspension corticosteroid nasal sprays become less viscous when shaken and sprayed, then return to a more viscous state after application. This time-dependent, reversible loss of viscosity under shear (e.g., shaking or spraying) can be quantified in the rheological property of thixotropy. The flow properties of 5 corticosteroid nasal sprays were measured over a range of shear rates. The formulations tested included Nasonex, Vancenase AQ, Nasacort AQ, Rhinocort Aqua, and Flonase. The yield stress values, as well as an estimate of thixotropy, were compared by using three different sampling techniques, including one that simulated patient use (shaking for 30 sec, spraying, and immediately transferring the sample to the rheometer). The rheological properties of all products indicated that when initially shaken and dispensed, they flowed more freely, followed by recovery of viscosity that would likely inhibit the suspensions from flowing out of the nasal cavity. Under all three tested conditions, Nasonex exhibited the highest yield stress, the largest apparent initial and final viscosities, and the highest apparent thixotropy. The study protocol that simulated patient-use conditions produced the following rank order of measured thixotropy: Nasonex > Flonase > Vancenase AQ > Rhinocort Aqua > Nasacort AQ. The thixotropy of Nasonex was 3.4 to 21.4 times greater and the final viscosity was 3.2 to 17.4 times greater than the values of the other tested products. Journal ISSN: 0363-9045 Issue: 29-9 (2003) Pages: 1005-12

[Anal and palmar contact dermatitis caused by iodopropynyl butylcarbamate in moist sanitary wipes]
[Anal and palmar contact dermatitis caused by iodopropynyl butylcarbamate in moist sanitary wipes] A 63-year old man developed severe perianal and palmar contact dermatitis caused by sensitization to iodopropynyl butylcarbamate in moist sanitary wipes. Iodopropynyl butylcarbamate is increasingly employed as preservative in common cosmetic formulations and moist sanitary wipes as substitute for the previously frequently used sensitizers isothiazolinones and methyldibromoglutaronitrile. The allergic potential of diverse preservatives is a serious problem for the cosmetic industry, since truly hypoallergenic preservatives are not available but products such as moist sanitary wipes in large packages definitely require some form of protection. Journal ISSN: 0017-8470 Issue: 54-10 (2003) Pages: 970-4

Features of mometasone furoate nasal spray and its utility in the management of allergic rhinitis.
Features of mometasone furoate nasal spray and its utility in the management of allergic rhinitis. Mometasone furoate aqueous nasal spray (NS; Nasonex, Schering Corporation), is a synthetic corticosteroid approved for the prophylaxis and treatment of seasonal allergic rhinitis (SAR) and the treatment of perennial allergic rhinitis (PAR) in patients >or= 12 years of age, and for the treatment of SAR and PAR in children as young as 2 years of age. Studies demonstrate that mometasone furoate NS is a potent, clinically effective and well-tolerated intranasal corticosteroid with negligible systemic activity and which offers the convenience of once-daily dosing. Journal ISSN: 1465-6566 Issue: 4-9 (2003) Pages: 1579-91

Effects of medical or surgical castration on erectile function in an animal model.

Effects of medical or surgical castration on erectile function in an animal model. The goal of this study was to investigate the effects of medical castration (luteinizing hormone-receptor hormone [LH-RH] agonist treatment) or surgical castration on erectile function in an animal model. New Zealand White male rabbits were either kept intact (control); surgically orchiectomized; or treated for 2, 4, or 8 weeks with the LH-RH agonist leuprolide acetate (107 microg/kg/mo). At 2 weeks, plasma testosterone levels of orchiectomized and leuprolide acetate-treated animals were 12.8% and 57.4% of intact control animals, respectively. Erectile function was assessed by continuously recording systemic arterial pressure (SAP) and intracavernosal blood pressure (ICP) and determining the ICP:SAP ratios in response to electrical stimulation of the pelvic nerve at varying frequencies (2.5-32 Hz). Androgen deprivation by surgical (orchiectomy) or medical (leuprolide acetate) castration reduced ICP at all frequencies tested but did not alter SAP. Administration of the phosphodiesterase type 5 inhibitor vardenafil (10 microg/kg) did not enhance ICP in surgically orchiectomized or leuprolide acetate-treated animals. Nitric oxide synthase and arginase activities in the corpus cavernosum were not significantly altered by surgical or medical castration. Further, Masson trichrome staining of erectile tissue from androgen-ablated animals showed a reduction in smooth muscle content. These data demonstrate that androgen deprivation achieved by surgical or medical castration adversely affects penile hemodynamics and erectile function without producing significant changes in the activities of nitric oxide synthase or arginase. We conclude that androgen deprivation produces structural alterations in the corpus cavernosum leading to corporal veno-occlusive dysfunction. Journal ISSN: 0196-3635 Issue: 24-3 (2003 May-Jun) Pages: 381-7

Eletriptan treatment of migraine in patients switching from barbiturate-containing analgesics: results from a multiple-attack study.
Eletriptan treatment of migraine in patients switching from barbiturate-containing analgesics: results from a multiple-attack study. The aim of this study was to examine efficacy and tolerability of eletriptan in patients switched from barbiturate-containing combinations (Fiorinal), Fioricet. Migraineurs (n = 160) meeting IHS criteria, with unsatisfactory response in the past year to butalbital-containing combinations, treated up to 16 attacks over 3 months with eletriptan 40 mg. Assessments included headache response and pain-free rates and functional impairment at baseline and 2 h postdose, and global ratings of treatment satisfaction at 24 h. At 2 h postdose, average headache response and pain-free rates were 71% (95% CI, 69-74%) and 37% (95% CI, 35-40%), respectively; 68.5% of patients (95% CI, 65-72%) reported functional response. Within-patient analysis found no efficacy diminution over time (no tolerance). Average headache recurrence rate was 20% (95% CI, 18-23%). Eletriptan was well-tolerated; 6 (3.7%) patients discontinued due to adverse events. There were no serious treatment-related adverse events. We conclude that in poor responders to butalbital-caffeine combinations, switching to eletriptan 40 mg was well-tolerated and efficacious. Journal ISSN: 0333-1024 Issue: 25-9 (2005) Pages: 726-34

High dose fluticasone propionate, 1 mg daily, versus fluticasone propionate, 2 mg daily, or budesonide, 1.6 mg daily, in patients with chronic severe asthma. International Study Group.
High dose fluticasone propionate, 1 mg daily, versus fluticasone propionate, 2 mg daily, or budesonide, 1.6 mg daily, in patients with chronic severe asthma. International Study Group. Airway inflammation is now regarded as fundamental in the pathogenesis of asthma and treatment with inhaled corticosteroids has proved effective. There is a need for drugs in this category with higher topical potency but fewer side-effects than those presently available. A double-blind, parallel group study was conducted in 671 patients with severe asthma (already taking between 0.8-2.0 mg of inhaled corticosteroid daily) to compare the safety and efficacy of 6 weeks of treatment with inhaled fluticasone propionate (FP), 1 mg daily, to fluticasone propionate, 2 mg daily, and budesonide (BUD), 1.6 mg daily, delivered via a metered-dose inhaler. Peak expiratory flow (PEF), asthma symptoms, and usage of rescue medication were recorded daily by the patient. At each clinic visit (-2, 0, 3 and 6 weeks) morning serum cortisol levels, bone markers and spirometry were assessed. The changes in mean morning PEF from baseline (weeks 1-6) were: FP 2 mg daily +24 l.min-1; FP 1 mg daily +21 l.min-1; BUD 1.6 mg daily +13 l.min-1. A similar rank order for the three treatments was seen for evening PEF, clinic spirometry, reduction of diurnal PEF variation, symptom scores, and requirement for rescue bronchodilators. The mean serum cortisol levels remained well within the normal range in all three groups. Analysis of the geometric mean cortisol ratio (treatment/baseline ratio after 6 weeks treatment) showed a changed rank order, the values being: FP 1 mg daily 1.04; BUD 1.6 mg daily 0.97; FP 2 mg daily 0.88.(ABSTRACT TRUNCATED AT 250 WORDS) Journal ISSN: 0903-1936 Issue: 8-4 (1995) Pages: 579-86

Private prescription costs for sildenafil within the NHS: a telephone survey.

Private prescription costs for sildenafil within the NHS: a telephone survey. Because of the restrictions on prescribing for impotence within the NHS, doctors routinely write private prescriptions for sildenafil. The aim of this study was to determine the variation in cost of a private prescription of four 100 mg tablets of sildenafil. A selection of different pharmacy types within five areas in England was surveyed. We telephoned a total of 86 pharmacies and we were quoted prices ranging from pounds 28.20 to pounds 42.33. There was a significant difference in price between area and between pharmacy type. Best prices are not necessarily found at the major pharmacy chains or hospital pharmacies, as might be expected. NHS doctors and patients need to be aware of this significant difference in cost. Journal ISSN: 0956-4624 Issue: 15-5 (2004) Pages: 314-5

Weight gain and cardiovascular risk factors during smoking cessation with bupropion or nicotine.
Weight gain and cardiovascular risk factors during smoking cessation with bupropion or nicotine. Weight gain is frequent after smoking cessation, and may limit patient's will to quit and long-term success. Nicotine and bupropion are effective drugs for smoking withdrawal. However, their influence on weight gain, insulin resistance and other cardiovascular risk factors, as well as possible differences in obese and lean subjects, have not been fully evaluated. We randomised 25 lean and 25 obese smokers to receive either bupropion or nicotine patches. Clinical evaluation and lipid profile were performed at baseline and after treatment. Insulin resistance was also assessed at the end. Weight, BMI, waist-to-hip ratio, and diastolic blood pressure increased (p < 0.005), whereas lipid profile improved (p < 0.001) after smoking cessation independently of obesity at baseline or drug used. Obese patients had higher insulin resistance at the end (p < 0.05) regardless of drug used. Weight gain was inversely related to age (beta= - 0.125, R = 0.38, p = 0.046), and insulin resistance was related to obesity at baseline (beta = 0.85, R = 0.46, p = 0.02). In conclusion, weight gain after smoking cessation is not dependent on obesity or drug taken. A beneficial lipid profile is achieved after quitting smoking with either bupropion or nicotine patch in both obese and lean subjects. Journal ISSN: 0018-5043 Issue: 36-3 (2004) Pages: 178-82

Bupropion sustained release treatment reduces fatigue in cancer patients.
Bupropion sustained release treatment reduces fatigue in cancer patients. OBJECTIVE: To demonstrate that bupropion sustained release (SR) can reduce the symptoms of fatigue experienced by cancer patients. METHOD: We studied an open-label case series of outpatients with fatigue referred for psychiatric assessment from a tertiary care cancer centre. Inclusion criteria were the presence of fatigue or depression with marked fatigue. Clinical status was assessed using the Global Clinical Improvement scale. RESULTS: Fifteen subjects with various cancer sites and psychiatric diagnoses were treated with bupropion SR (modal dose 150 mg) for up to 2 years. Most (13 of 15) saw improvement. Thirteen patients had minor, expectable side effects, and 10 patients were able to continue with bupropion for an extended time. All subjects who improved showed improvement within 2 to 4 weeks. CONCLUSIONS: This is the first report that shows bupropion SR can reduce fatigue in cancer patients. Controlled studies with more homogeneous samples would be necessary to establish the efficacy of this intervention. Further studies should address whether this effect of bupropion is separate from its action as an antidepressant. Journal ISSN: 0706-7437 Issue: 49-2 (2004) Pages: 139-44

[Changes in the circadian rhythm of respiratory activity in "depressive" rats as affected by tricyclic antidepressants]

[Changes in the circadian rhythm of respiratory activity in "depressive" rats as affected by tricyclic antidepressants] At chronic administration imipramine (10 and 25 mg/kg) and amitriptyline (10 mg/kg) shift the acrophase of the circadian rhythm of the rest-activity cycles in rats for a later time of the day. On the contrary, repeated injections of reserpine led to the rhythm acrophase shift for an earlier time and this effect is less pronounced against the background of the antidepressants. The effects of imipramine and amitriptyline are more distinct in the animals which exhibit signs of "depressiveness" in the open field and are more sensitive to the agents according to the forced swimming test. Journal ISSN: 0014-8318 Issue: 51-3 (1988 May-Jun) Pages: 5-8

Improving depression severity assessment--I. Reliability, internal validity and sensitivity to change of three observer depression scales.
Improving depression severity assessment--I. Reliability, internal validity and sensitivity to change of three observer depression scales. The Hamilton Depression Scale (HAMD) is the most commonly used scale for depression severity assessment and for antidepressant treatment evaluation. Alternative scales have been proposed by Bech and Rafaelsen (BRMS) and by Montgomery and Asberg (MADRS) to try to overcome the shortcomings of HAMD: they are based on different concepts of severity and different scaling procedures. Comparisons with respect to reliability, validity and ability to detect change have been performed using these scales in different samples. The BRMS proved superior. This result makes it necessary to question the usual procedure of testing the efficacy of antidepressants by means of HAMD alone. Problems in defining the severity of depression and in testing the validity of severity scales are discussed. Journal ISSN: 0022-3956 Issue: 22-1 (1988) Pages: 3-12

Vardenafil (Levitra) for erectile dysfunction: a systematic review and meta-analysis of clinical trial reports.
Vardenafil (Levitra) for erectile dysfunction: a systematic review and meta-analysis of clinical trial reports. Trials of the efficacy and safety of vardenafil in the treatment of male erectile dysfunction (ED) were meta-analysed. All available databases were searched (January 1, 2001-November 30, 2003). Trials were eligible if they included men with ED, compared vardenafil with placebo, were randomized, were at least of 12 weeks duration, and assessed clinically relevant outcomes. Two reviewers independently evaluated study quality and extracted data in a standardized fashion. Nine trials (6809 men) met the inclusion criteria. In results pooled from seven fixed-dose trials, vardenafil increases the Erectile Function domain of the International Index of Erectile Function questionnaire by 6.18 units (weighted mean difference (WMD)). Vardenafil also increases the percentage of erections firm enough to allow vaginal penetration (WMD: 26) and the percentage of sexual attempts that were successful per participant (WMD: 29.8). The percentage of men agreeing with the statement that @apos;the treatment they have been taking over the past 4 weeks improved their erections@apos;, is also in favour of vardenafil (relative risk (RR): 3). These efficacy variables appeared greater at higher doses, although there are no significant differences between 10 and 20 mg dose. The same results were extracted for the two flexible @apos;as needed@apos; dosing trials. Discontinuations are greater at the vardenafil groups compared to placebo (RR: 2.25). Specific adverse events with vardenafil included flushing, dyspepsia, headache, and rhinitis. Vardenafil was not significantly associated with serious cardiovascular events or death. Vardenafil, in all treatment regimens, shows to possess superior efficacy to placebo in the treatment of patients with erectile dysfunction. More data is needed on patients@apos; subgroups. Journal ISSN: 0955-9930 Issue: 16-6 (2004) Pages: 470-8

The effects of nonsteroidal anti-inflammatory drugs on blood pressures of patients with hypertension controlled by verapamil.
The effects of nonsteroidal anti-inflammatory drugs on blood pressures of patients with hypertension controlled by verapamil. BACKGROUND: Nonsteroidal anti-inflammatory drugs may attenuate the antihypertensive effects of diuretics, beta-blockers, angiotensin-converting enzyme inhibitors, central alpha-agonists, and other vasodilators. Their effects on the antihypertensive efficacy of calcium channel blockers are inadequately studied in small numbers of patients but appear to be minimal. METHODS: A three-phase, randomized, double-blind, placebo-controlled multicenter study included 162 patients aged 18 to 75 years with essential hypertension. After diastolic blood pressure was controlled to 90 mm Hg or less with once-daily verapamil hydrochloride, patients received ibuprofen, naproxen, or placebo matching capsules for 3 weeks, and blood pressure, heart rate, weight, and adverse effects were evaluated. A general linear model with 95% confidence intervals was used to compare each nonsteroidal anti-inflammatory drug treatment group with the placebo group. RESULTS: No significant differences in sitting, standing, or supine blood pressure were noted with naproxen or ibuprofen compared with placebo. The percentages of patients in each treatment group with increases of 10 mm Hg or more in either systolic or diastolic blood pressure were similar. Statistically significant increases in weight were seen with both nonsteroidal anti-inflammatory drug therapies. Changes in pulse rate were not significant. The incidence of adverse effects was similar across all three treatment groups. CONCLUSIONS: The addition of naproxen or ibuprofen to the treatment of hypertensive patients in whom blood pressure is controlled by once-daily verapamil does not cause an increase in blood pressure. Verapamil may therefore offer considerable advantages in maintaining control of blood pressure in patients who regularly receive nonsteroidal anti-inflammatory drug therapy. Journal ISSN: 0003-9926 Issue: 155-10 (1995) Pages: 1049-54

Potency, selectivity, and consequences of nonselectivity of PDE inhibition.
Potency, selectivity, and consequences of nonselectivity of PDE inhibition. Phosphodiesterases (PDEs) play a decisive role in cyclic nucleotide-mediated intracellular signaling. As PDEs are expressed in a variety of tissues, selectivity is a prerequisite for a therapeutically applicable PDE inhibitor. Sildenafil, vardenafil, and tadalafil are selective for PDE5, with vardenafil exhibiting the highest potency and minimal inhibition of other PDEs, with the exception of PDE6. Tadalafil is extremely selective for PDE5, but also potently inhibits PDE11, an enzyme with unknown physiological function. As PDE1 is expressed in the brain, myocardium, and vascular smooth muscle cells, nonselectivity with respect to this enzyme (selectivity: tadalafil>vardenafil>sildenafil) may result in vasodilation and tachycardia. Inhibition of PDE6 (selectivity: tadalafil>vardenafil congruent with sildenafil), which is expressed only in retina and functions in visual transduction, can transiently disturb vision. PDE5 inhibitors may also indirectly inhibit PDE3 by increasing cyclic guanosine monophospate levels, thereby elevating heart rate and vasodilation while inhibiting platelet aggregation. Journal ISSN: 0955-9930 Issue: 16 Suppl 1- (2004) Pages: S11-4

Effects of cetirizine on the delayed K+ currents in cardiac cells: comparison with terfenadine.

Effects of cetirizine on the delayed K+ currents in cardiac cells: comparison with terfenadine. 1. The aim of the present experiments was to analyse the effect of the H1-histamine antagonist, cetirizine, on the delayed K+ currents in cardiac cells and to compare its effects with another H1-histamine antagonist terfenadine, known to possess proarrhythmic effects. 2. Whole cell currents were measured by use of the single electrode patch-clamp technique in rabbit and guinea-pig myocytes. 3. The activation relationship for the IKr current in rabbit ventricular myocytes was depressed and its voltage-dependence shifted in the negative direction with a V1/2 value -13.4+/-2.4 mV under control conditions which changed to -19.1+/-1.9 mV (n=4) in the presence of 0.1 mM cetirizine. 4 In rabbit ventricular myocytes the IC50 for block of IKr was 108+/-8 microM (n=5); in guinea-pig ventricular myocytes this concentration of cetirizine reduced the rapidly activating component IKr to 49+/-4.5% (n=5), while the slowly activating IKs was less affected and only inhibited to 79+/-2.3% (n=5). 5 The block of IKr did not show use-dependence and the time course of the tail current was not changed, suggesting rested-state block or fast activated-state block and no rapid recovery on deactivation. No important difference was found in the activity of the two enantiomers of cetirizine. 6 Terfenadine in comparison was more potent in blocking IKr, the IC50 being 96+/-15 nM (n=6). 7 Based on the present results and information in the literature on binding, it was concluded that cetirizine is a relatively selective H1-histamine receptor antagonist, with minor effects on K+ currents. The IC50 concentration for IKr block in heart cells was 1.000 times higher than the concentrations needed to block H1 histamine receptors. The occurrence of cardiac arrhythmias due to K+ current blockade is therefore unlikely with this drug. Journal ISSN: 0007-1188 Issue: 124-4 (1998) Pages: 663-8

Store-operated calcium influx in human gastric cells: role of endogenous prostaglandins.
Store-operated calcium influx in human gastric cells: role of endogenous prostaglandins. BACKGROUND: Store-operated calcium influx (SOCI) appears to be a key component in regulating processes such as gene expression and cellular metabolism in nonexcitable cells. Our objective was to determine what effect, if any, prostaglandin inhibition had on SOCI in human gastric cells. METHODS: SOCI was induced in human gastric cells (AGS) with thapsigargin, a microsomal Ca++ adenosine triphosphatase inhibitor. Quantitation of SOCI was achieved by two different methods: sustained intracellular calcium elevation and manganese (Mn++) uptake. Endogenous prostaglandin E2 (PGE2) synthesis was measured by enzyme immunoassay. Three different nonsteroidal anti-inflammatory drugs (NSAIDs; indomethacin, ibuprofen, and aspirin) were used to minimize the nonspecific actions of any individual agent. RESULTS: SOCI in AGS cells was inhibited by the store-operated Ca+2 channel blocker lanthanum (La+3) but not the voltage-operated Ca+2 channel antagonists verapamil or nifedipine. Each of the three NSAIDs equally inhibited SOCI. The inhibition of SOCI induced by indomethacin was partially reversed by the addition of exogenous PGE2. Finally, AGS cells exposed to thapsigargin demonstrated significantly increased endogenous PGE2 release. CONCLUSIONS: These data suggest that NSAIDs inhibit (or endogenous prostaglandins modulate) SOCI in human gastric cells, at least in part. Because SOCI appears to be a critical mechanism involved in cell proliferation, this may provide one explanation of how NSAIDs inhibit (and endogenous prostaglandins enhance) gastric epithelial renewal and repair. Journal ISSN: 0039-6060 Issue: 124-2 (1998) Pages: 429-37

Treatment of erectile dysfunction.
Treatment of erectile dysfunction. Erectile dysfunction (ED) is an inability to attain or maintain an erection sufficient for satisfactory sexual intercourse. It is an undertreated and underdiagnosed condition that can be due to vasculogenic, neurogenic, hormonal and psychogenic factors. Effective treatment of ED should restore quality of life and allow patients to return to the sex life they had before. Current therapeutic options include non-pharmacological treatments, locally administered drugs and oral therapies. The oral phosphodiesterase-5 (PDE5) inhibitors are considered first-line treatments of ED and have revolutionized ED management in the last five years. Three PDE5 inhibitors are currently available, sildenafil, vardenafil and tadalafil. They are all effective with similar efficacy and good safety profiles. However, tadalafil has the added benefit of a broad window opportunity offering patients more freedom to choose when to initiate sexual activity. Journal ISSN: 0956-4624 Issue: 15-4 (2004) Pages: 215-21

Emerging oral drugs for erectile dysfunction.
Emerging oral drugs for erectile dysfunction. Erectile dysfunction (ED) is a common medical condition that affects the sexual life of millions of men worldwide. Many drugs are now available for the treatment of ED, with oral pharmacotherapy representing the first-line option for most patients. Sildenafil citrate, an inhibitor of the enzyme phosphodiesterase type 5 (PDE5), is the most widely prescribed oral agent and has a very satisfactory efficacy-safety profile in all patient categories. Tadalafil (Cialis; Eli Lilly & Co., ICOS) and vardenafil (Levitra; Bayer Pharmaceuticals, GlaxoSmithKline) are new PDE5 inhibitors that have recently been approved worldwide. Both have been associated with significant positive efficacy-safety profiles. Apomorphine sublingual is a dopamine D1 and D2 receptor agonist, which has been approved for marketing in Europe. It is best selected for treating patients with mild-to-moderate ED, but it is seldom used in clinical practice due to its limited efficacy and side effects, particularly nausea. Patients who do not respond to oral pharmacotherapy or who are unable to use it are appropriate candidates for intracavernosal and intraurethral therapy. The efficacy of second-line treatment is high, but the attrition rate remains significant. For the purpose of this review, clinical and pharmacological analysis focuses on the recent advances in the field of oral therapy, including PDE5 inhibitors and sublingual apomorphine. Journal ISSN: 1744-7623 Issue: 9-1 (2004) Pages: 179-89

High-performance liquid chromatography with a column-switching system and capillary electrophoresis for the determination of ibuprofen in plasma.
High-performance liquid chromatography with a column-switching system and capillary electrophoresis for the determination of ibuprofen in plasma. Quantitative aspects of high-performance liquid chromatography with a column-switching system (CSS-HPLC) and capillary electrophoresis (CE) were investigated for the determination of ibuprofen in plasma. For CSS-HPLC, 100 microl of plasma was directly injected onto the column system for the three separation steps: (1) deproteinization and fractionation of plasma samples with a polymer-coated mixed-function phase column, (2) concentration with an intermediate column and (3) final separation with a main column. For CE, a mixture of 50 microl of plasma and 1 ml of acetonitrile was centrifuged and the supernatant was introduced onto the capillary (66 cmX50 microm I.D.; 62 cm to detector) at 20 degrees C. Run buffer was 250 mM sodium borate buffer (pH 8.5) and applied electric field was 379 V cm(-1). Linear dynamic ranges were 0.1-250 microg ml(-1) in CSS-HPLC and 1-1000 microg ml(-1) in CE. Intra-day and inter-day coefficients of variation were less than 5.6% and 6.5% for CSS-HPLC, 6.3% and 6.5% for CE, respectively. The limits of detection (S/N=3) for CSS-HPLC and CE were 25 ng ml(-1) and 300 ng ml(-1), respectively. CSS-HPLC was superior in simplicity and sensitivity, while CE was better in efficiency, rapidity, and cost. Journal ISSN: 1387-2273 Issue: 712-1-2 (1998) Pages: 153-60

Release kinetics of liposome-encapsulated ganciclovir after intravitreal injection in rabbits.

Release kinetics of liposome-encapsulated ganciclovir after intravitreal injection in rabbits. This study was undertaken to establish experimentally whether the intravitreal application of liposomally-entrapped ganciclovir could prolong intraocular therapeutic levels when it is compared to the intravitreal injection of a simple solution of the drug. New Zealand white rabbits were given an intravitreal injection of the drug solution and of liposome-encapsulated ganciclovir. The intravitreal clearance of ganciclovir was determined after a single injection of either the drug solution (200 micrograms/0.1 mL) or the liposomally-entrapped (with 41% load; 82 micrograms drug load and 118 micrograms free) ganciclovir. The ganciclovir vitreal concentrations were measured at various time intervals for a period up to 43 days using an HPLC method. The results of this study clearly demonstrated that prolonged intravitreal drug levels (above the mean inhibitory dose of cytomegalovirus of 1 microgram/mL) after administration of the liposome-entrapped ganciclovir and estimated to continue beyond 30-43 days. The injection of the 200 micrograms/0.1 mL of drug solution showed a mean vitreous concentration which was higher than the ID50 only for 55 h. The disappearance rate constant for the liposome-encapsulated injections was approximately 22 x slower than simple drug solution injections (controls). No evidence of retinal toxicity was found by clinical or light microscopy examination of the treated eyes. Journal ISSN: 0265-2048 Issue: 13-4 (1996 Jul-Aug) Pages: 473-80

Vardenafil, a new phosphodiesterase type 5 inhibitor, in the treatment of erectile dysfunction in men with diabetes: a multicenter double-blind placebo-controlled fixed-dose study.
Vardenafil, a new phosphodiesterase type 5 inhibitor, in the treatment of erectile dysfunction in men with diabetes: a multicenter double-blind placebo-controlled fixed-dose study. OBJECTIVE: This study evaluated the efficacy and safety of vardenafil treatment for erectile dysfunction (ED) in men with diabetes. RESEARCH DESIGN AND METHODS: In this prospective multicenter double-blind placebo-controlled fixed-dose parallel-group phase III trial, 452 patients with diabetes (type 1 or type 2) and ED were randomized to take 10 or 20 mg vardenafil or placebo as needed for 12 weeks. Efficacy responses were assessed by International Index of Erectile Function domain scores, rates of vaginal penetration and successful intercourse, and a global assessment question (GAQ) about erection improvement during the previous 4 weeks. RESULTS: After 12 weeks of treatment, a dose-dependent (P = 0.02) improvement in erections was noted for the GAQ, with 57 and 72% of men taking 10 mg or 20 mg vardenafil, respectively, reporting improved erections, in contrast to 13% after taking placebo (P < 0.0001). For the erectile function domain, dose-dependent (P = 0.03) final scores for the 10- and 20-mg dose were 17.1 and 19.0 compared with 12.6 for placebo (P < 0.0001). Both vardenafil doses significantly enhanced the rates of successful penetration (P < 0.0001) and successful intercourse (P < 0.0001) compared with placebo. Vardenafil treatment was effective in increasing intercourse success rates at all levels of baseline ED severity, at each level of plasma HbA(1c), and for type 1 and 2 diabetes. Treatment-emergent adverse events were primarily mild to moderate headache (

Phosphodiesterase type 5 inhibitors for the treatment of erectile dysfunction in patients with diabetes mellitus.
Phosphodiesterase type 5 inhibitors for the treatment of erectile dysfunction in patients with diabetes mellitus. Sildenafil, a phosphodiesterase 5 (PDE5) inhibitor, has become a first-line therapy for diabetic patients with erectile dysfunction (ED). The efficacy in this subgroup, based on the Global Efficacy Question, is 56% vs 84% in a selected group of non-diabetic men with ED. Two novel PDE5 inhibitors, tadalafil (Lilly ICOS) and vardenafil (Bayer), have recently completed efficacy and safety clinical trials in @apos;general@apos; and diabetic study populations and are now candidates for US FDA approval. A summary analysis of the phase three clinical trials of sildenafil, tadalafil and vardenafil in both study populations is presented to provide a foundation on which the evaluation of the role of the individual PDE5 inhibitors for the treatment of patients with ED and DM can be built. Journal ISSN: 0955-9930 Issue: 14-6 (2002) Pages: 466-71

The effect of vardenafil, a potent and highly selective phosphodiesterase-5 inhibitor for the treatment of erectile dysfunction, on the cardiovascular response to exercise in patients with coronary artery disease.
The effect of vardenafil, a potent and highly selective phosphodiesterase-5 inhibitor for the treatment of erectile dysfunction, on the cardiovascular response to exercise in patients with coronary artery disease. OBJECTIVES: The effect of vardenafil, a potent and highly selective phosphodiesterase-5 (PDE5) inhibitor, on symptom-limited exercise time, time to first awareness of angina, and time to ischemic threshold (ST-segment depression > or =1 mm from baseline) during exercise tolerance testing (ETT) was examined in patients with stable coronary artery disease (CAD). BACKGROUND: Erectile dysfunction (ED) is common among men with CAD. PDE5 inhibition is increasingly the preferred treatment option for ED. However, the effect of PDE5 inhibition on exercise-induced ischemia in CAD patients has received limited prospective evaluation. METHODS: In this double-blind, crossover, single-dose multicenter study, 41 men with reproducible stable exertional angina due to ischemic CAD received vardenafil 10 mg or placebo, followed by ETT (5 to 10 metabolic equivalents [METS], Bruce protocol) 1 h postdose. Sublingual nitrate use was prohibited for > or =24 h pre- and postexercise study days. End points included symptom-limited treadmill exercise time, time to first awareness of angina, time to ischemic threshold, and safety. RESULTS: Relative to placebo, vardenafil 10 mg did not alter exercise treadmill time (427 +/- 105 s vs. 433 +/- 109 s, p = 0.39), or time to first awareness of angina (292 +/- 110 s vs. 291 +/- 123 s, p = 0.59), but significantly prolonged time to ischemic threshold (334 +/- 108 s vs. 381 +/- 108, p = 0.0004). At peak exercise, vardenafil 10 mg did not alter blood pressure, heart rate, or rate-pressure product relative to placebo. The most common adverse events (facial flushing and headache) were of mild or moderate intensity, and short-lived. CONCLUSIONS: Vardenafil 10 mg did not impair the ability of patients with stable CAD to exercise at levels equivalent or greater than that attained during sexual intercourse (average of 2.5 to 3.3 METS). Journal ISSN: 0735-1097 Issue: 40-11 (2002) Pages: 2006-12

Non-narcotic analgesic dose and risk of incident hypertension in US women.
Non-narcotic analgesic dose and risk of incident hypertension in US women. Acetaminophen, ibuprofen, and aspirin are the most commonly used drugs in the United States. Although the frequency of their use has been associated with hypertension, prospective data examining the dose of these drugs and risk of hypertension are lacking. Furthermore, whether certain indications for analgesic use, particularly headache, mediate the association is unclear. We conducted 2 prospective cohort studies among older women 51 to 77 years of age (n=1903) from the Nurses' Health Study I and younger women 34 to 53 years of age (n=3220) from the Nurses' Health Study II who completed detailed supplemental questionnaires pertaining to their analgesic use and who did not have hypertension at baseline. We analyzed incident hypertension according to categories of average daily dose of acetaminophen, nonsteroidal anti-inflammatory drugs, and aspirin. Information on indications for analgesic use as well as relevant confounders was also gathered prospectively. Compared with women who did not use acetaminophen, the multivariable adjusted relative risk for those who took >500 mg per day was 1.93 (1.30 to 2.88) among older women and 1.99 (1.39 to 2.85) among younger women. For nonsteroidal anti-inflammatory drugs, similar comparisons yielded multivariable relative risks of 1.78 (1.21 to 2.61) among older women and 1.60 (1.10 to 2.32) among younger women. These associations remained significant among women who did not report headache. Aspirin dose was not significantly associated with hypertension. Higher daily doses of acetaminophen and nonsteroidal anti-inflammatory drugs independently increase the risk of hypertension in women. Because acetaminophen and nonsteroidal anti-inflammatory drugs are commonly used, they may contribute to the high prevalence of hypertension in the United States. Journal ISSN: 1524-4563 Issue: 46-3 (2005) Pages: 500-7

Enteropathy-type T-cell lymphoma showing repeated small bowel rupture and refractoriness to chemotherapy: a case report.

Enteropathy-type T-cell lymphoma showing repeated small bowel rupture and refractoriness to chemotherapy: a case report. The majority of gastrointestinal lymphomas arise in the stomach, whereas lymphomas occurring in the intestine are relatively rare and a limited fraction of them show the T-cell phenotype with clinical manifestations similar to de novo celiac disease. Enteropathy-type T-cell lymphoma is extremely rare in Japan, presumably owing to the very low incidence of celiac disease among the Japanese population. Here, we report a 66-year-old Japanese male who was diagnosed as having enteropathy-type T-cell lymphoma preceded by diarrhea and intermittent bloody stool for over 1 year. He was admitted to our hospital as an emergency case because of panperitonitis due to intestinal perforation. After immediate partial small-bowel resection, cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) chemotherapy was started. However, the disease was highly refractory and was exacerbated with leukemic transformation. Subsequent salvage chemotherapy could not be completed because of the formation of spontaneous jejuno-abdominal fistula, followed by fatal septic shock. Particular attention should be paid to the peculiar clinical manifestations of enteropathy-type T-cell lymphoma such as malnutrition, frequent intestinal perforation and refractoriness to chemotherapy. Journal ISSN: 0368-2811 Issue: 32-12 (2002) Pages: 546-9

Biochemical effects of the antidepressant paroxetine, a specific 5-hydroxytryptamine uptake inhibitor.
Biochemical effects of the antidepressant paroxetine, a specific 5-hydroxytryptamine uptake inhibitor. Paroxetine was shown to be a potent (Ki = 1.1 nM) and specific inhibitor of [3H]-5-hydroxytryptamine (5-HT) uptake into rat cortical and hypothalamic synaptosomes in vitro. Lineweaver-Burk kinetic analysis determined that this inhibition was competitive in nature, implying a direct interaction with the 5-HT uptake transporter complex. Oral administration of paroxetine produced a dose-related inhibition of [3H]-5-HT uptake (ED50 = 1.9 mg/kg) into rat hypothalamic synaptosomes ex vivo with little effect on [3H]-l-noradrenaline (NA) uptake (ED50 greater than 30 mg/kg). This selectivity for 5-HT uptake was maintained after oral dosing for 14 days. Paroxetine (ED50 1-3 mg/kg PO) prevented the 5-HT depleting effect of p-chloroamphetamine (PCA) in rat brain, demonstrating 5-HT uptake blockade in vivo. Radioligand binding techniques in rat brain in vitro showed that paroxetine has little affinity for alpha 1, alpha 2 or beta adrenoceptors, dopamine (D2), 5-HT1, 5-HT2 or histamine (H1) receptors at concentrations below 1000 nM. Paroxetine demonstrated weak affinity for muscarinic receptors (Ki = 89 nM) but was at least 15 fold weaker than amitriptyline (Ki = 5.1 nM). Paroxetine, therefore, provides a useful pharmacological tool for investigating 5-HT systems and furthermore should be an antidepressant with reduced tricyclic-like side-effects. Journal ISSN: 0033-3158 Issue: 93-2 (1987) Pages: 193-200

Effects of the selective 5-hydroxytryptamine uptake inhibitors paroxetine and zimeldine on EEG sleep and waking stages in the rat.
Effects of the selective 5-hydroxytryptamine uptake inhibitors paroxetine and zimeldine on EEG sleep and waking stages in the rat. The effects of oral paroxetine and zimeldine on EEG sleep-waking phases in the rat were investigated over a wide dose range. To ascertain that at the doses used for the EEG studies paroxetine and zimeldine selectively affect the serotoninergic system, their effects on brain 5-hydroxytryptamine (5-HT), dopamine and noradrenaline were determined. It was found that paroxetine and zimeldine at doses of 1-18 mg/kg dose-dependently prolonged waking and shortened slow-wave sleep and paradoxical sleep. In the same dose range cortical 5-HT turnover was significantly reduced, whereas the other aminergic systems were not influenced. These results suggest that 5-HT uptake inhibitors increase vigilance in rats at oral doses which selectively stimulate the serotoninergic system. Journal ISSN: 0302-282X Issue: 17-4 (1987) Pages: 206-12

Eosinophil markers in seasonal allergic rhinitis. Intranasal fluticasone propionate inhibits local and systemic increases during the pollen season.

Eosinophil markers in seasonal allergic rhinitis. Intranasal fluticasone propionate inhibits local and systemic increases during the pollen season. BACKGROUND: The purpose was to study activation markers of the eosinophil granulocytes in seasonal allergic rhinitis, and the impact of topical steroid therapy thereupon. METHODS: Sixty-three rhinitis patients with monoallergy to grass were examined before and at peak pollen season. Blood eosinophil count, eosinophil cationic protein (ECP), and eosinophil peroxidase (EPO) in serum and nasal lavage fluid were measured. During the season, patients were randomized to treatment with intranasal fluticasone propionate 0.1 mg o.d. (n=26), 0.2 mg o.d. (n=25), or placebo (n=12). Six healthy persons served as controls. RESULTS: During the season, all parameters, except nasal lavage ECP, increased in the placebo group (P

A comparison of the efficacy of fluticasone propionate aqueous nasal spray and loratadine, alone and in combination, for the treatment of seasonal allergic rhinitis.
A comparison of the efficacy of fluticasone propionate aqueous nasal spray and loratadine, alone and in combination, for the treatment of seasonal allergic rhinitis. BACKGROUND: Intranasal corticosteroids and oral antihistamines are both effective in the treatment of seasonal allergic rhinitis, although the therapeutic value of administering the two types of agents concurrently has rarely been evaluated. This study was designed to compared the efficacy, safety, and impact on quality of life of fluticasone propionate aqueous nasal spray (FP ANS), loratadine, FP ANS plus loratadine, and placebo (an aqueous nasal spray plus tablet) in the treatment of seasonal allergic rhinitis during the mountain cedar allergy season in south central Texas. METHODS: Six hundred patients with seasonal allergic rhinitis were treated for 2 weeks with either FP ANS 200 microgram once daily, loratadine 10 mg once daily, the FP ANS and loratadine regimens combined, or placebo in a multicenter, randomized, double-blind, double-dummy, parallel-group study. RESULTS: Clinician- and patient-rated total and individual nasal symptom scores after 7 and 14 days of therapy and overall evaluations were significantly lower (P < .001) in the FP ANS and FP ANS plus loratadine groups compared with the loratadine only and placebo groups. Loratadine was not statistically different from placebo in clinician and patient symptom score ratings nor in overall clinician and patient evaluations. FP ANS plus loratadine and FP ANS monotherapy were comparable in efficacy in almost all evaluations; for some patient-rated symptoms the combination was found superior. Mean score changes in the Rhinoconjunctivitis Quality of Life Questionnaire from baseline to day 14 showed significantly greater improvement (P < .001) in quality of life in the FP ANS group than in the group of patients receiving loratadine only or placebo and no significant benefit was demonstrated in the FP ANS plus loratadine group over the FP ANS monotherapy group. No serious or unusual drug-related adverse events were reported. Combining loratadine with FP ANS did not alter the adverse events profile or frequency. Journal ISSN: 0094-3509 Issue: 47-2 (1998) Pages: 118-25

Fluoxetine and tics in an adolescent.
Fluoxetine and tics in an adolescent. OBJECTIVE: To describe a case of tics associated with fluoxetine. CASE SUMMARY: A depressed adolescent was treated with fluoxetine. The patient had not been exposed to any other pharmacologic agents prior to this treatment. Following eight months of fluoxetine therapy the patient developed numerous tics. The movements subsided six months after discontinuation of fluoxetine. DISCUSSION: Antidopaminergic effects have been reported in patients treated with fluoxetine. Because fluoxetine is a specific serotonin reuptake inhibitor, one plausible explanation for the extrapyramidal symptoms observed in these patients is that serotonin modulates dopaminergic neurons. CONCLUSIONS: Extrapyramidal symptoms have been reported in patients receiving fluoxetine, although never previously in an adolescent. This case report provides further evidence that fluoxetine may be associated with severe extrapyramidal adverse reactions. Journal ISSN: 1060-0280 Issue: 27-6 (1993) Pages: 725-6

A randomized double-blind study of fluoxetine versus placebo in the treatment of dysthymia.
A randomized double-blind study of fluoxetine versus placebo in the treatment of dysthymia. OBJECTIVE: The purpose of this study was to assess the efficacy of fluoxetine, a selective serotonergic antidepressant, in the treatment of dysthymia. METHOD: Thirty-five patients who met criteria for dysthymia, but not major depression, began randomized, double-blind 8-week trials of fluoxetine or placebo. RESULTS: Of 32 patients who completed the study, 10 (62.5%) of the 16 patients given fluoxetine and three (18.8%) of the 16 given placebo responded to treatment. Response was defined as 1) 50% or greater decrease in Hamilton Rating Scale for Depression score and 2) a score of 1 or 2 on the Clinical Global Impression (CGI) improvement subscale. Fluoxetine subjects showed significantly greater improvement at week 8 than placebo subjects on the Hamilton depression and CGI scales, but not on the Hopkins Symptom Check-list (58-item) or the Cornell Dysthymia Rating Scale. CONCLUSIONS: When compared to placebo, fluoxetine showed short-term effectiveness in treating dysthymic symptoms. Journal ISSN: 0002-953X Issue: 150-8 (1993) Pages: 1169-75

Combination of bupropion, paroxetine and quetiapine as adjuvant treatment for multiple myeloma.
Combination of bupropion, paroxetine and quetiapine as adjuvant treatment for multiple myeloma. Multiple myeloma is a severe plasma dyschrasia with no known treatment or cure, even bone marrow transplantation. Cytokines such as tumor necrosis factor-alpha (TNF) and interleukin-6 (Il-6) are thought to be important trophic factors for the malignant plasma cells. In turn, histamine and nitric oxide are positive regulatory factors for Il-6. Here we note that the safe, approved and commonly used psychiatric medicines bupropion (Wellbutrin), paroxetine (Paxil) and quetiapine (Seroquel) are respectively potent TNF, nitric oxide and histamine antagonists and thus might find some use in treatment of multiple myeloma. Journal ISSN: 0306-9877 Issue: 62-5 (2004) Pages: 817-8

Prenatal cocaine exposure potentiates paroxetine-induced desensitization of 5-HT2A receptor function in adult male rat offspring.
Prenatal cocaine exposure potentiates paroxetine-induced desensitization of 5-HT2A receptor function in adult male rat offspring. This study investigated the ability of prenatal exposure to cocaine to alter serotonin(2A) (5-HT(2A)) receptor function and paroxetine-induced desensitization of 5-HT(2A) receptor function in rat offspring. Following exposure to saline or (-)cocaine (15 mg/kg, s.c., b.i.d.), during gestational days 13-20, adult male offspring were treated with either saline or paroxetine (10 mg/kg/day, i.p. 14 days). Eighteen hours post-treatment, changes in the stimulation of oxytocin, adrenocorticotropic hormone (ACTH) and corticosterone by (-)4-iodo-2,5-dimethoxyphenylisopropylamine (DOI, 0.5 or 2.0 mg/kg, s.c.) and in 5-HT(2A) receptor densities were determined. Prenatal cocaine exposure did not alter 5-HT(2A) receptor-mediated neuroendocrine responses or 5-HT(2A) receptor densities. In contrast, paroxetine treatment reduced cortical 5-HT(2A) receptors (18-25%) and desensitized 5-HT(2A) receptor-mediated oxytocin responses in both offspring groups. Furthermore, in cocaine offspring, paroxetine produced an inhibition of 5-HT(2A) receptor-mediated increase in plasma ACTH levels and a greater attenuation of the oxytocin responses to (-)DOI. Paroxetine-induced reductions in body weight gain (-8.8%) were comparable in both offspring groups. These data, demonstrating that prenatal exposure to cocaine potentiates paroxetine-induced desensitization of 5-HT(2A) receptor function, may be clinically relevant with respect to treating mood disorders in adults exposed in utero to cocaine. Journal ISSN: 0028-3908 Issue: 46-7 (2004) Pages: 942-53

Syndrome of inappropriate secretion of antidiuretic hormone secondary to fluoxetine.
Syndrome of inappropriate secretion of antidiuretic hormone secondary to fluoxetine. OBJECTIVE: To report a case of possible fluoxetine-induced syndrome of inappropriate antidiuretic hormone secretion (SIADH). CASE SUMMARY: A 92-year-old patient was prescribed oral fluoxetine 20 mg daily for depression. After 13 days of therapy, she developed severe weakness and was found to have hyponatremia. Fluoxetine was discontinued. Treatment included fluid restriction and sodium chloride and potassium supplementation. Eight days after admission, the hyponatremia resolved and the patient was discharged without any pharmacologic treatment for depression. DISCUSSION: Case reports on fluoxetine-induced SIADH were reviewed. Fluoxetine-associated SIADH appears to occur most commonly after short-term therapy in elderly patients. Resolution of hyponatremia occurs six days to two weeks after discontinuation of fluoxetine. CONCLUSIONS: Geriatric patients receiving fluoxetine should be monitored regularly to detect abnormal electrolyte values. Journal ISSN: 1060-0280 Issue: 27-6 (1993) Pages: 723-4