Oral famciclovir for the suppression of recurrent genital herpes: a randomized controlled trial. Collaborative Famciclovir Genital Herpes Research Group

CONTEXT: Recurrent genital herpes simplex virus (HSV) may be treated episodically, but this may not be sufficient for patients with frequent recurrences. OBJECTIVE: To determine the efficacy and safety of famciclovir in the suppression of recurrent genital HSV infection. DESIGN: A randomized, double-blind, placebo-controlled, parallel-group study. SETTING: Thirty university, hospital, or private outpatient referral centers in Canada and Europe. PATIENTS: A total of 455 patients (223 men, 232 women) aged 18 years or older with a history of 6 or more episodes of genital herpes during 12 of the most recent 24 months, in the absence of suppressive therapy, received study medication. INTERVENTION: Oral famciclovir, 125 mg or 250 mg 3 times daily or 250 mg twice daily, or placebo for 52 weeks. MAIN OUTCOME MEASURES: Time to the first recurrence of genital HSV infection; the proportion of patients remaining free of HSV recurrence at 6 months; frequency of adverse events. RESULTS: In an intent-to-treat analysis, famciclovir significantly delayed the time to the first recurrence of genital herpes at all dose regimens (hazard ratios, 2.9-3.3; P<.001); median time to recurrence for famciclovir recipients was 222 to 336 days compared with 47 days for placebo recipients. The proportion of patients remaining free of HSV recurrence was approximately 3 times higher in famciclovir recipients (79%-86%) than in placebo recipients (27%) at 6 months (relative risks, 2.9-3.1; P<.001); efficacy was maintained at 12 months. Famciclovir was well tolerated with an adverse experience profile comparable to placebo. CONCLUSIONS: Oral famciclovir (125 mg or 250 mg 3 times daily or 250 mg twice daily) is an effective, well-tolerated treatment for the suppression of genital HSV infection in patients with frequent recurrences.     

Study of the learning climate in a nursing college

Likopide (N-acetylglucosamine-(beta 1-4)-N-acetylmuramyl-alanyl-D-isoglutamine) is a synthetic analog of muramylpeptides, characterized by immunomodulating properties and increasing the nonspecific resistance to infections. Seventy patients with ophthalmic herpes were examined, 35 of these were treated with likopide and 35 were administered placebo. Fifty-two of these suffered from stromal keratitis with ulceration and 18 had no ulcers. The trials were carried out by the double blind test with placebo. Likopide was administered orally in 10 mg tablets twice daily according to the following protocol: 3 days of treatment, 3-day interval, and 3-day treatment. All the patients were administered local specific (acyclovir ointment) and general symptomatic therapy. Immunological studies were carried out before and after therapy. Clinical assessment showed a reliably high therapeutic efficacy of likopide, its total value (excellent and good results) being as high as 88.5%. The mean duration of therapy with likopide was 11.4 +/- 0.4 days versus 15.2 +/- 0.9 days in the placebo group. Judging by the recovery criteria (arrest of inflammation, epithelization of the cornea, resorption of corneal infiltration and edema, resorption of iritis) likopide reliably accelerated healing and ensured a higher increase of vision acuity. Likopide reliably decreased the rate of detection of herpes simplex virus antigen in the involved eye conjunctiva in comparison with the placebo group patients (97.1% of negative cases versus 60%). The drug was well tolerated by the patients, no side effects were observed. Skin allergic tests with likopide showed no drug allergies.     

Imiquimod, a patient-applied immune-response modifier for treatment of external genital warts

Genital human papillomavirus infection is one of the most common sexually transmitted diseases. Imiquimod is a new agent, an immune-response modifier, that has been demonstrated to have potent in vivo antiviral and antitumor effects in animal models. The present prospective, multicenter, double-blind, randomized, vehicle-controlled trial evaluated the efficacy and safety of daily patient-applied imiquimod for up to 16 weeks for the treatment of external genital warts. Wart recurrence was investigated during a 12-week treatment-free follow-up period. In the intent-to-treat analysis, baseline warts cleared from 49 of 94 (52%) patients treated with 5% imiquimod cream, 13 of 90 (14%) patients treated with 1% imiquimod cream, and 3 of 95 (4%) vehicle-treated patients; the differences between the groups treated with vehicle and imiquimod were significant (P < 0.0001). For subjects who completed the follow-up period, recurrence rates after a complete response were 19% (9 of 48 patients) in the 5% imiquimod cream group, 17% (2 of 12) in the 1% imiquimod cream group, and 0% (0 of 3) in the vehicle-treated group. There were no systemic reactions, although local skin reactions (generally of mild or moderate severity) were common, particularly in the 5% imiquimod cream group. Local reactions caused two patients to discontinue treatment. The most frequently reported local skin reactions were erythema, excoriation or flaking, and erosion. Patient-applied 5% imiquimod cream is effective for the treatment of external genital warts and has a favorable safety profile.     

Peroral famciclovir in the treatment of experimental ultraviolet radiation-induced herpes simplex labialis: A double-blind, dose-ranging, placebo-controlled, multicenter trial

Three doses of famciclovir were tested for treatment of experimental ultraviolet radiation (UVR)-induced herpes labialis. Patients received 125, 250, or 500 mg of famciclovir or placebo 3 times a day for 5 days beginning 48 h after UVR exposure, a model of early episodic intervention. Of 248 patients irradiated, 102 developed lesions while on treatment. There were no significant differences between groups in the number of lesions. The mean maximal lesion size was reduced in a dose-proportional manner: 139, 105, 77, and 55 mm2 for the placebo and 125-, 250-, and 500-mg famciclovir groups, respectively (P=.040, linear regression). Median time to healing was faster in the 500-mg famciclovir group than in the placebo group, both by investigator (4 vs. 6 days, 33% reduction, P=.010) and patient assessment (3.0 vs. 5.8 days, 48% reduction, P=.008) analyses. These findings suggest that evaluation of higher drug doses for herpes labialis treatment is warranted.     

Detection of viral DNA to evaluate outcome of antiviral treatment of patients with recurrent genital herpes

Culture of infectious virus, PCR amplification of viral DNA, and the appearance of genital skin lesions were used as markers to study the course of a recurrence of genital herpes in 40 patients treated with famciclovir or placebo. The highest frequency of patients with skin lesions occurred within the first 36 h following the onset of a recurrence, which also corresponded to the peak in the production of virus. While the timing of the peak in skin lesions was independent of the type of treatment, the frequency of lesions and the release of virus at the lesion site were both reduced by famciclovir treatment. Furthermore, patients receiving this antiviral agent showed a more rapid recovery time and a shorter period during which viral DNA could be detected at the lesion. PCR and then Southern blot hybridization greatly enhanced our ability to detect herpes simplex virus at the lesion site. This procedure proved to be of greater diagnostic value in assessing genital herpes than the standard culture method currently used. In addition, PCR was more sensitive in evaluating treatment effectiveness.     

Recombinant interferon-alpha therapy for acute hepatitis B: a randomized, double-blind, placebo-controlled trial

In spite of the availability of hepatitis B vaccine, acute hepatitis B continues to be a worldwide problem for which no specific therapy is available. We investigated the safety and the effectiveness of recombinant interferon-alpha2b (rIFN-alpha2b) in the treatment of acute hepatitis B by determining overall severity and duration of symptoms, time required to clear viral antigens and hepatitis B virus (HBV) DNA, and titre of antibodies to hepatitis B surface antigen (HBsAb), 24 weeks after the onset of therapy. One hundred patients were randomly assigned to treatment with either 3 million units (MU) (n = 34) or 10 MU (n = 33) rIFN-alpha2b or to placebo (n = 33), three times weekly for 3 weeks. Follow-up was for 24 weeks. A significantly shorter duration of the symptoms and signs of acute hepatitis was observed in patients who received 3 MU rIFN-alpha2b compared with those who received 10 MU rIFN-alpha2b or placebo. Twenty-one weeks post-therapy, patients treated with 10 MU rIFN-alpha2b showed a significantly higher geometric mean HBsAb titre than those treated with placebo (85.1 vs 35.5 IU l-1, P < 0.05). rIFN-alpha2b administration was well tolerated even in jaundiced patients. No serious side-effects were observed necessitating reduction in dose or discontinuation of the drug. The effect of rIFN-alpha2b on transition of HBV infection to chronicity could not be evaluated in this trial because such an unfavourable course was not seen in any of the treated or the control patients. In conclusion, rIFN-alpha2b was safe in acute hepatitis B, and at low dose was found to ameliorate symptoms and to shorten significantly the duration of illness.     

Sulpiride infused into the nucleus accumbens posttraining impairs memory of spatial water maze training

A randomized, double-blind study of valaciclovir for suppression of recurrent genital herpes was conducted among 1479 immunocompetent patients. Patients were randomized to receive valaciclovir (250 mg, 500 mg, or 1 g once daily, or 250 mg twice daily), acyclovir (400 mg twice daily), or placebo, for 1 year. All valaciclovir dosages were significantly more effective than placebo at preventing or delaying recurrences (P < .0001). There was a dose-response relationship (P < .0001) across the once-daily valaciclovir regimens. Twice-daily valaciclovir and acyclovir were similar in effectiveness. Subgroup analysis showed that patients with a history of < 10 recurrences per year were effectively managed with 500 mg of valaciclovir once daily. One gram of valaciclovir once daily, 250 mg of valaciclovir twice daily, or 400 mg of acyclovir twice daily were more effective in patients with > or = 10 recurrences per year. Safety profiles of all treatments were comparable. Thus, valaciclovir is highly effective and well tolerated for suppression of recurrent genital herpes. Once-daily regimens offer a useful option for patients who require suppressive therapy for management of genital herpes.     

Acyclovir given as prophylaxis against oral ulcers in acute myeloid leukaemia: randomised, double blind, placebo controlled trial

OBJECTIVES: To evaluate (a) the prophylactic effect of the antiherpetic drug acyclovir on oral ulcers in patients with acute myeloid leukaemia receiving remission induction chemotherapy and thus (b), indirectly, the role of herpes simplex virus in the aetiology of these ulcers. DESIGN: Randomised, double blind, placebo controlled trial. SUBJECTS: 74 herpes simplex virus seropositive patients aged 18-84. Thirty seven patients received acyclovir (800 mg by mouth daily) and 37 placebo. The patients were examined daily for 28 days. MAIN OUTCOME MEASURES: Occurrence of herpes labialis, intraoral ulcers, and acute necrotising ulcerative gingivitis. RESULTS: The two populations were comparable in age, sex, type of antineoplastic treatment, and history of herpes labialis. Acute oral infections occurred in 25 of the acyclovir treated patients and 36 of the placebo treated patients (relative risk 0.69 (95% confidence interval 0.55 to 0.87)). This difference was due to a reduction in the incidence of herpes labialis (one case versus eight cases; relative risk 0.13 (0.02 to 0.95)), intraoral ulcers excluding the soft palate (one case versus 13 cases; relative risk 0.08 (0.01 to 0.56)), and acute necrotising ulcerative gingivitis (one case versus eight cases; relative risk 0.13 (0.02 to 0.95)). However, ulcers on the soft palate were diagnosed with similar frequency in the two groups. Isolation of herpes simplex virus type 1 in saliva was reduced from 15 cases in the placebo group to one case in the acyclovir group (relative risk 0.07 (0.01 to 0.48)). CONCLUSION: Intraoral ulcers excluding the soft palate are most often due to infection with herpes simplex virus, whereas ulcers on the soft palate have a non-herpetic aetiology. The findings suggest that acute necrotising ulcerative gingivitis may also be due to herpes simplex virus. Prophylaxis with acyclovir should be considered for patients with acute myeloid leukaemia during remission induction therapy.     

Labeling of penicillamine di sulfide with technetium-99m

OBJECTIVE: To compare the safety and efficacy of 1% SDZ ASM 981 cream and a matching placebo cream in the treatment of patients with moderate atopic dermatitis. DESIGN: A randomized, double-blind, placebo-controlled, right-and-left comparison study. SETTING: Academic referral center. PATIENTS: Thirty-four adult patients with moderate atopic dermatitis. INTERVENTION: Topical 1% SDZ ASM 981 cream was applied twice daily (n=16) or once daily (n=18) and compared with a corresponding placebo cream base. MAIN OUTCOME MEASURES: Efficacy was measured using a 4-point (0-3) scale for erythema, pruritus, exudation, excoriation, and lichenification (Atopic Dermatitis Severity Index [ADSI]). The ADSI score was defined as the sum of these 5 ratings (range, 0-15) and was determined on the pretreatment day (1 to 14 days before day 0) and on days 0, 2, 4, 7, 9, 11, 14, 16, 18, and 21. The percentage change from baseline (day 0) in the ADSI score was calculated on each of these days. Safety was evaluated by monitoring of adverse events, physical examination, hematologic examination, clinical chemistry studies, urinalysis, and measurement of blood levels of SDZ ASM 981. RESULTS: Of the 38 patients recruited, 34 started and 28 completed treatment according to the protocol. Sixteen patients used the cream twice daily, with significant improvement after 2 days of treatment. Within 3 weeks of topical therapy with 1% SDZ ASM 981 cream twice daily, a mean reduction of 71.9% in the ADSI score was observed at the actively treated test sites compared with a mean reduction of 10.3% at the placebo-treated test sites (P<.001). Efficacy was significantly less in the group treated once daily (n=18), with mean reductions of 37.7% and 6.2%, respectively. The efficacy was especially apparent for pruritus and excoriation. There were no clinically relevant drug-related adverse effects. CONCLUSIONS: Treatment with 1% SDZ ASM 981 cream was well tolerated. Twice-daily application of 1% SDZ ASM 981 cream was significantly more effective than use of the corresponding placebo and more effective than once-daily treatment. The new macrolactam ascomycin derivative SDZ ASM 981 is a promising agent for the treatment of patients with atopic dermatitis. More elaborate phase 2 and 3 trials are under way to fully investigate the potential of this medication.     

Percutaneous absorption of ibuprofen from different formulations. Comparative study with gel, hydrophilic ointment and emulsion cream

In a three-way cross-over study on 6 healthy adult volunteers, the percutaneous absorption of ibuprofen (CAS 15687-27-1) was studied with 3 topical formulations containing 5% w/w ibuprofen in a gel (Iprogel) or in a hydrophilic ointment or in an emulsion cream. By analysis of the plasma drug concentrations appearing after topical application, the relative drug bioavailability was calculated in terms of Cmax (maximum blood concentration of the drug), AUC (area under the curve of drug plasma concentrations at various time points) and Tmax (the time required for appearance of maximum drug concentration in the blood). The gel formulation showed the highest drug concentration in blood, reached in the shortest period, whereas that from the hydrophilic ointment showed the lowest drug concentration, reached at the slowest rate. The absorption from the reference product containing the drug as an o/w emulsion cream was less than with the gel formulation but higher than that found with the hydrophilic ointment.     

Risk and outcome in metastatic malignant melanoma patients receiving DTIC, cisplatin, BCNU and tamoxifen followed by immunotherapy with interleukin 2 and interferon alpha2a

Combined chemo-/immunotherapy has shown high objective response rates and a significant though small proportion of long-term complete responders in metastatic malignant melanoma. The purpose of this study was to determine response rates, freedom from treatment failure (FFTF) and overall survival in patients with advanced metastatic malignant melanoma treated with combined chemo-/immunotherapy, and to determine the value of a prognostic model for prediction of treatment outcome, FFTF and survival. Sixty-nine patients with metastatic malignant melanoma received combined chemo-/immunotherapy consisting of up to four cycles of DTIC (220 mg m(-2) i.v. days 1-3), cisplatin (35 mg m(-2) i.v. days 1-3), BCNU (150 mg m(-2) i.v. day 1, cycles 1 and 3 only) and tamoxifen (20 mg orally, daily). Two cycles of chemotherapy were followed by 6 weeks of outpatient immunotherapy with combined interleukin 2 (20 x 10(6) IU m(-2) days 3-5, weeks 1 and 4; 5 x 10(6) IU m(-2) days 1, 3, 5, weeks 2, 3, 5, 6) and interferon-alpha (6 x 10(6) IU m(-2) s.c. day 1, weeks 1 and 4; days 1, 3, 5, weeks 2, 3, 5, 6). All patients were evaluated on an intention-to-treat basis. Of 69 patients entered in the study, seven achieved complete remissions and 20 reached partial remissions with an objective response rate of 39% (95% confidence interval 28-52%). Median survival was 11 months, median FFTF was 5 months. Seven patients achieved ongoing long-term remissions, with maximum survival of 58 + months, and maximum FFTF of 58 + months. By Kaplan-Meier survival analysis and two-proportional Cox regression analysis, pretreatment performance status and serum lactic dehydrogenase were statistically significant and independent predictors of survival; risk groups could be defined as (a) the absence of both or (b) the presence of either one or both of these risk factors. Whereas survival and response were significantly influenced by patient risk, no influence could be demonstrated for FFTF. This combined outpatient chemo-/immunotherapy is feasible and results in objective response rates and survival similar to earlier trials. Pretreatment risk, as defined by serum lactate dehydrogenase (LDH) and performance status, has a significant impact on treatment outcome and patient survival.     

Comparison of once-daily doses of omeprazole (40 and 20 mg) and placebo in the treatment of benign gastric ulcer: a multicenter, randomized, double-blind study

OBJECTIVE: The purpose of this multicenter, randomized, double-blind study, conducted in 520 patients, was to compare the efficacy and safety of omeprazole (40 and 20 mg once daily) with placebo in the treatment of benign gastric ulcer. METHODS: Treatment with omeprazole or placebo lasted 4 wk; those whose ulcers remained unhealed continued the same treatment regimen for an additional 4 wk. The effects of therapy were determined by endoscopy and assessment of GI symptoms. Safety and tolerability were evaluated through reported adverse events, physical examinations, and laboratory tests. RESULTS: At weeks 4 and 8, the proportion of patients with healed ulcers was significantly greater in the omeprazole 40- and 20-mg groups than in the placebo group (p < 0.01). At week 8, the healing rate was significantly greater in the 40-mg group than in the 20-mg group (82.7 vs 74.8%, p < 0.05). In patients with large ulcers (>1 cm), the 40-mg regimen was associated with a significantly higher healing rate (78.9%) than both the 20-mg regimen (61.4%) and placebo (34.6%) at week 8 (p < 0.05 vs omeprazole 20 mg; p < 0.01 vs placebo). Healing rates in patients with small ulcers were similar for the 40- and 20-mg groups. Omeprazole was well tolerated, with no significant differences versus placebo in the overall incidence of clinical or laboratory adverse events. CONCLUSIONS: Omeprazole 40 and 20 mg, administered once daily, healed a significantly greater proportion of patients than did placebo. The 40-mg regimen offered significant advantages over the 20-mg regimen in patients with large ulcers.     

A blinded, randomized, paired, placebo-controlled trial of 20-minute EMLA cream to reduce the pain of peripheral i.v. cannulation in the ED

A eutectic mixture of local anesthetics (EMLA) in cream form has been used as a topical anesthetic to reduce the pain of procedures penetrating the skin. It is generally applied for 45 to 60 minutes before the painful procedure. The purpose of this study was to determine whether a 20-minute application of EMLA is useful in reducing the pain of routine peripheral intravenous cannulation in the emergency department (ED). A blinded, randomized, placebo-controlled, paired trial compared the pain of intravenous cannulation in both hands of study subjects: one hand was treated with 20-minute EMLA cream and the other hand was treated with 20-minute placebo cream. Forty subjects identified the more painful hand and scored pain measurements of each hand using a 10-cm visual analog scale. These data failed to demonstrate any significant benefit of EMLA compared with placebo. EMLA is not useful for intravenous cannulation when used for 20-minute application times. There may be more effective and less costly ways of reducing the pain of intravenous cannulation that patients would prefer.     

Platelet-aggregation inhibition and hemodynamic effects of beraprost sodium, a new oral prostacyclin derivative: a study in healthy male subjects

The antiaggregation and hemodynamic effects of the new prostacyclin analogue beraprost sodium were investigated in a randomized, placebo-controlled, double-blind clinical trial of Latin-square design. Twelve healthy Caucasian males randomly received 8-day oral treatments of 20, 40, and 60 micrograms of beraprost sodium and a placebo. One-week washout periods followed each treatment. Pharmacokinetic and pharmacodynamic measurements were performed on days 1 and 8 for each period of treatment. All three doses of beraprost sodium significantly inhibited platelet aggregation on day 8 (compared with placebo) during the 1st h after drug intake. Incubation of the 60-micrograms beraprost sodium samples with ADP (2, 5, and 10 microM) and collagen (1.25 micrograms/mL) decreased platelet aggregation by 10, 19, 16, and 6 +/- 4% (mean +/- SE), respectively, compared with placebo. No significant hemodynamic effects on blood pressure, heart rate, and digital pulse were observed. The 60-micrograms dose of beraprost sodium did significantly decrease the IRZ index (which may reflect the left ventricular pre-ejection period) on days 1 and 8. Some subjects experienced headache and facial flushing, effects that were dose dependent and reversible. Beraprost sodium at 20- to 60-micrograms doses exerts platelet antiaggregation (day 8 of therapy) and slight hemodynamic (days 1 and 8 of treatment) effects in Caucasian males. Beraprost sodium hemodynamic effects and potential benefits in patients with cardiovascular disease should be explored further.     

Differential responses to chemoimmunotherapy in patients with metastatic malignant melanoma

An open, multicentre non-randomised study was performed to evaluate the activity and toxicity of combination chemoimmunotherapy, consisting of cisplatin, interleukin-2 and interferon-alpha, in metastatic malignant melanoma. Between March 1992 and September 1993, 28 patients with pathologically proven metastatic malignant melanoma, bidimensionally measurable disease and an Eastern Co-operative Oncology Group score < or = 1 were treated with the combination chemoimmunotherapy. The regimen consisted of cisplatin (100 mg/m2 on day 0), interleukin-2 (Proleukin, Chiron, Middlesex, U.K.) 18 x 10(6)IU/m2/d continuous intravenous infusion on days 3-7 and 17-22, with interferon-alpha (Roferon-A, Roche, Hertfordshire, U.K.) 9 x 10(6) U/d subcutaneously on days 3, 5, 7, 17, 19, 21 during the interleukin-2 infusions. The treatment cycle lasted 28 days. Among 27 assessable patients, 5 patients achieved partial responses, for an overall response rate of 18% (95% CI 6-37%). Median progression-free survival was 44 days (range 8-279) and median overall survival was 264 days (range 41-1432). Differential responses were noted in 41% of patients and responses were more frequent in non-visceral disease (skin, lymph node and soft tissue disease) (P = 0.04). These results indicate that differential responses to chemoimmunotherapy are common in patients with metastatic melanoma. This may account for the broad range of response rates reported in the literature.     

Time trend of female breast carcinoma in situ by race and histology in Connecticut, USA

BACKGROUND: Surgical procedures used to remove genital warts (cryotherapy, electrodesiccation) are painful. Attempts to reduce the discomfort of surgery by prior lidocaine infiltration anesthesia are compromised by the pain of the infiltration. OBJECTIVE: Our purpose was to determine the efficacy of topically applied lidocaine/prilocaine cream to reduce the pain of lidocaine infiltration and the pain associated with cryotherapy to remove genital warts. METHODS: Men, scheduled for removal of genital warts by cryotherapy, were randomly selected to receive one of three treatments: (1) lidocaine/prilocaine cream application, (2) 1% lidocaine infiltration, and (3) lidocaine/prilocaine cream application followed by infiltration of 1% lidocaine. RESULTS: Application of lidocaine/prilocaine cream for 15 minutes markedly reduced the pain of lidocaine infiltration. The combination of lidocaine/prilocaine cream followed by infiltration of 1% lidocaine gave greater pain relief from the cryotherapy than did either anesthetic alone. CONCLUSION: The application of lidocaine/prilocaine cream as an adjunct to lidocaine infiltration reduced the pain of infiltration and the pain associated with cryotherapy for the removal of genital warts.     

Psychological aspects of genital human papillomavirus infection: a preliminary report

Genital human papillomavirus (HPV) infection can lead to self-inflicted blame and hypochondriac fears as well as to problems with sexuality. The aim of this study was to assess the psychological and psychodynamic aspects of patients with widespread genital HPV infection entering into a clinical trial in which they were randomly assigned to three treatment groups: CO2 laser ablation, intramuscular interferon-alpha, CO2 laser ablation plus intramuscular interferon-alpha. Fifty-one patients were studied. Patients were asked to take a series of questionnaires which included a self-rating questionnaire for gathering information on sexuality, emotional relationship with the partner and social life. A visual analog scale was used to rate intensity of pain during sexual intercourse. Each patient went also through an in-depth interview with a clinical psychologist and filled out two personality tests to measure depression (CDQ = IPAT depression test) and anxiety (ASQ = IPAT anxiety test). Results indicated a high percentage of sexual impairments after therapy (28 cases), presence of fear of cancer (14 cases) and worsenings in the emotional relationship with the partner. No difference was found among groups of treatment.     

Recombinant human erythropoietin reduces the need for erythrocyte and platelet transfusions in pediatric patients with sarcoma: a randomized, double-blind, placebo-controlled trial

OBJECTIVE: To evaluate the effect of recombinant human erythropoietin (EPO) and iron supplementation on transfusion requirements in pediatric patients with sarcoma who were receiving chemotherapy, we performed a double-blind, placebo-controlled, randomized trial. METHODS: Twenty-four pediatric patients with malignant solid tumors were randomly assigned to receive either placebo (saline solution) or EPO for a 16-week study period. The starting dose was 150 IU/kg per dose three times a week and was escalated by 50 IU/kg per dose increments monthly until packed red blood cell (PRBC) transfusion independence was achieved or a dosage of 300 IU/kg per dose was reached. Iron supplementation was prescribed at a dose of 6 mg of elemental iron per kilogram daily. The primary study end point was the comparison of PRBC transfusion requirements in the two groups. RESULTS: Of 24 patients, 20 were evaluable for response. The median PRBC transfusion requirement during the 16-week period was 23 ml/kg in EPO-treated patients versus 80 ml/kg in placebo patients (p = 0.02). The median number of single-donor platelet units transfused was zero in the EPO-treated patients compared with four in the placebo group (p = 0.005). No statistical difference in the intensity of bone marrow suppression was seen, as measured by the median number of complete blood cell counts with an absolute neutrophil count of < 1000 cells/microliter. CONCLUSIONS: Treatment with EPO and iron significantly reduces PRBC transfusions in pediatric patients receiving concomitant chemotherapy for malignant sarcomas. A decrease in the number of platelet transfusions was also seen and deserves further study.     

Free and total insulin-like growth factors and insulin-like growth factor binding proteins during 14 days of growth hormone administration in healthy adults

The objective was to investigate the effect of growth hormone (GH) administration on circulating levels of free insulin-like growth factors (IGFs) in healthy adults. Eight healthy male subjects were given placebo and two doses of GH (3 and 6 IU/m2 per day) for 14 days in a double-blind crossover study. Fasting blood samples were obtained every second day. Free IGF-I and IGF-II were determined by ultrafiltration of serum. Total IGF-I and IGF-II were measured after acid-ethanol extraction. In addition, GH, insulin, IGF binding protein 1 (IGFBP-1) and IGFBP-3 were measured. Serum-free and total IGF-I increased in a dose-dependent manner during the 14 days of GH administration. After 14 days, serum-free IGF-I values were 610 +/- 100 ng/l (mean +/- SEM) (placebo), 2760 +/- 190 ng/l (3 IU/ m2) and 3720 +/- 240 ng/l (6 IU/m2) (p = 0.0001 for 3 and 6 IU/m2 vs placebo; p = 0.004 for 3 IU/m2 vs 6 IU/m2). Total IGF-I values were 190 +/- 10 micrograms/l (placebo), 525 +/- 10 (3 IU/m2), and 655 +/- 40 micrograms/l (6 IU/m2) (p < 0.0001 for 3 and 6 IU/m2 vs placebo; p = 0.04 for 3 IU/m2). There were no differences in the levels of free or total IGF-II during the three study periods. Insulin-like growth factor binding protein 1 was decreased during GH administration (p = 0.04 for placebo vs 3 IU/m2; p = 0.006 for placebo vs 6 IU/m2). In conclusion, fasting serum free IGF-I increased dose dependently during GH administration and free IGF-I increased relatively more than total IGF-I. This may partly be due to the decrease in IGFBP-1.