Group Received Combination Therapy Research Articles

Thermal moxibustion combined with omeprazole in the treatment of gastroesophageal reflux disease

Objecifive To explore the clinical efficacy of thermal moxibustion combined with omeprazole for gastroesophageal reflux disease ( GERD ).Methods 200 patients with GERD who visited our clinic from February 2010 to December 2011 were randomly divided into study group and control group.The study group received combination therapy with thermal moxibustiou and omeprazole while the control group received omeprazole alone.The clinical efficacy and adverse reactions were observed in the two groups.Results There was significant difference between the two groups in the total effectiveness rate ( 92.00％ vs.73.00％,P＜ 0.05 ).No adverse reactions were found in the study group; whereas sicchasia occurred in 5 patients ( 5.00％ ) diarrhea in 3 ( 3.00％ ),and dizziness in 8 ( 8.00％ ) in the control gorup.Conclusions Combination therapy with thermal moxibustion and omeprazole for gastroesophageal reflux disease is effective and has fewer adverse reactions.It is worth popularizing clinically. Key words: Thermal moxibustion; Omeprazole; Gastroesophageal reflux disease

18F-FDG PET/CT Imaging Detects Therapy Efficacy of Anti-EMMPRIN Antibody and Gemcitabine in Orthotopic Pancreatic Tumor Xenografts

The objective of this study is to evaluate the therapeutic response to a novel monoclonal antibody targeting human extracellular matrix metalloproteinase inducer (EMMPRIN) in combination with gemcitabine in a pancreatic-tumor xenograft murine model by sequential 2-deoxy-2-[18F]fluoro-D-glucose ((18)F-FDG) positron emission tomography/computed tomgraphy (PET/CT) imaging. Four groups of SCID mice bearing orthotopic pancreatic tumor xenografts were injected with phosphate-buffered saline, gemcitabine (120 mg/kg BW), anti-EMMPRIN antibody (0.2 mg), or combination, respectively, twice weekly for 2 weeks, while (18)F-FDG PET/CT imaging was performed weekly for 3 weeks. Changes in mean standardized uptake value (SUV(mean)) of (18)F-FDG and volume of tumors were determined. The tumor SUV(mean) change in the group receiving combination therapy was significantly lower than those of the other groups. Tumor-volume changes of groups treated with anti-EMMPRIN monotherapy or combined therapy were significantly lower than that of the control group. These data provide support for clinical studies of anti-EMMPRIN therapy with gemcitabine for pancreatic cancer treatment.

The Role of Baseline Blood Pressure in Guiding Treatment Choice

Baseline blood pressure (BP) is a strong predictor of response to antihypertensive therapy and the patient's ability to reach BP goals. The objective of this study was to evaluate the role of baseline BP as a determinant of systolic BP (SBP) and treatment outcome to assist in the choice of initial therapy. This was a double-blind, placebo-controlled clinical trial (n = 1329) in patients with essential hypertension (mean sitting diastolic BP [DBP] > or = 95 mmHg and <110 mmHg) who were randomized to placebo, valsartan 160 mg, valsartan 320 mg, hydrochlorothiazide (HCTZ) 12.5 mg, HCTZ 25 mg, valsartan/HCTZ 160 mg/12.5 mg, valsartan/HCTZ 320 mg/12.5 mg or valsartan/HCTZ 320 mg/25 mg. Retrospective analyses were performed to determine mean BP at end of study and BP goal rates and to explore the relationship between baseline BP level and predicted final BP. The final SBP and DBP were lowest in the combination therapy groups across all baseline BPs and in subgroups of patients categorized by age (> or = 65 years, <65 years), race/ethnicity (White, Black, other), and severity of hypertension at baseline. The proportion of patients achieving the SBP goal of <140 mmHg was highest in the valsartan/HCTZ 320 mg/25 mg group; the overall SBP goal achievement rate was 85%, and 78% of participants with stage 2 hypertension achieved goal. By comparison, 59% of patients in the HCTZ 25 mg group and 52% in the valsartan 320 mg group achieved SBP goal. Initial combination therapy was associated with lower predicted final SBP and DBP at all baseline BP levels compared with monotherapy. Analysis of tolerability data revealed that the proportion of patients experiencing dizziness or discontinuing therapy due to adverse events was generally similar across treatment groups, whereas the BP-lowering efficacy was greatest in the groups receiving combination therapy. These secondary analyses suggest that characterizing the relationship between baseline SBP and achieved SBP can assist in the choice of initial therapy in a broad hypertensive population. Initial therapy with the combination of valsartan/HCTZ is more effective than monotherapy in lowering BP at all baseline BP levels, is consistent in this respect among all subgroups, and is well tolerated.

Renal Tissue Damage After Experimental Pyelonephritis: Role of Anti-Oxidants and Selective Cyclooxygenase-2 Inhibitors

Purpose Our aim was to examine the effect of anti-oxidant and selective cyclooxygenase-2 inhibitor therapy given adjunct to the conventional treatment of acute pyelonephritis on renal tissue damage. Material and Methods 48 wistar rats were divided into 4 groups according to their treatment modalities which were started one day after inoculation of all rats with 0.1 ml of E.Coli(ATCC 25922 1010 cfu/ml).First group received only antibiotic treatment with ceftriaxone(50 mg/kg, IM), second and third group received L-Carnitine(500 mg/kg, IM) and Meloxicam(.mg/kg,IM) in addition to the conventional treatment, respectively. Fourth group received combination therapy(L-Carnitine and Meloxicam)in addition to group one. 3 and 7 days after E.Coli inoculation rats were sacrificed and kidney samples were obtained for histologic determination of tubular atrophy, acute and chronic inflammation, interstitial fibrosis and biochemical determination of catalase activity(CAT), total antioxidant capacity(TAC) and malondialdehyde(MDA). Results Interstitial fibrosis(p:0.06),chronic inflammation(p:0.536) and tubular atrophy(p:0.094) decreased in group 4 compared to the other groups but there was statistically significant decrease only in acute inflammation(p:0.015). In addition,if the day of nephrectomy is considered, there was again a significant decrease in acute inflammation findings in day 7 compared to day 3 in group 2,3 and 4(p:0.002). CAT significantly increased in group 2(p:0.029),group 3(p:0.02) and group 4(p:0.014) and decreased in group 1(p:0.012) in day 7. Conclusions Acute renal inflammatory injury can be prevented much more effectively by combination therapy than conventional therapy. This process is probably due to the prevention of free oxygen radical generation by anti-oxidants and inhibition of chemotaxis by selective cyclooxygenase-2 inhibitors.

Renal Tissue Damage After Experimental Pyelonephritis: Role of Anti-Oxidants and Selective Cyclooxygenase-2 Inhibitors

Purpose Our aim was to examine the effect of anti-oxidant and selective cyclooxygenase-2 inhibitor therapy given adjunct to the conventional treatment of acute pyelonephritis on renal tissue damage. Material and Methods 48 wistar rats were divided into 4 groups according to their treatment modalities which were started one day after inoculation of all rats with 0.1 ml of E.Coli (ATCC 25922 1010 cfu/ml).First group received only antibiotic treatment with ceftriaxone (50 mg/kg, IM), second and third group received L-Carnitine (500 mg/kg, IM) and Meloxicam (.mg/kg, IM) in addition to the conventional treatment, respectively. Fourth group received combination therapy (L-Carnitine and Meloxicam) in addition to group one. 3 and 7 days after E.Coli inoculation rats were sacrificed and kidney samples were obtained for histologic determination of tubular atrophy, acute and chronic inflammation, interstitial fibrosis and biochemical determination of catalase activity (CAT), total antioxidant capacity (TAC) and malondialdehyde (MDA). Results Interstitial fibrosis (p:0.06), chronic inflammation (p:0.536) and tubular atrophy (p:0.094) decreased in group 4 compared to the other groups but there was statistically significant decrease only in acute inflammation (p:0.015). In addition,if the day of nephrectomy is considered, there was again a significant decrease in acute inflammation findings in day 7 compared to day 3 in group 2,3 and 4 (p:0.002). CAT significantly increased in group 2 (p:0.029),group 3 (p:0.02) and group 4 (p:0.014) and decreased in group 1 (p:0.012) in day 7. Conclusions Acute renal inflammatory injury can be prevented much more effectively by combination therapy than conventional therapy. This process is probably due to the prevention of free oxygen radical generation by anti-oxidants and inhibition of chemotaxis by selective cyclooxygenase-2 inhibitors. Our aim was to examine the effect of anti-oxidant and selective cyclooxygenase-2 inhibitor therapy given adjunct to the conventional treatment of acute pyelonephritis on renal tissue damage. 48 wistar rats were divided into 4 groups according to their treatment modalities which were started one day after inoculation of all rats with 0.1 ml of E.Coli (ATCC 25922 1010 cfu/ml).First group received only antibiotic treatment with ceftriaxone (50 mg/kg, IM), second and third group received L-Carnitine (500 mg/kg, IM) and Meloxicam (.mg/kg, IM) in addition to the conventional treatment, respectively. Fourth group received combination therapy (L-Carnitine and Meloxicam) in addition to group one. 3 and 7 days after E.Coli inoculation rats were sacrificed and kidney samples were obtained for histologic determination of tubular atrophy, acute and chronic inflammation, interstitial fibrosis and biochemical determination of catalase activity (CAT), total antioxidant capacity (TAC) and malondialdehyde (MDA). Interstitial fibrosis (p:0.06), chronic inflammation (p:0.536) and tubular atrophy (p:0.094) decreased in group 4 compared to the other groups but there was statistically significant decrease only in acute inflammation (p:0.015). In addition,if the day of nephrectomy is considered, there was again a significant decrease in acute inflammation findings in day 7 compared to day 3 in group 2,3 and 4 (p:0.002). CAT significantly increased in group 2 (p:0.029),group 3 (p:0.02) and group 4 (p:0.014) and decreased in group 1 (p:0.012) in day 7. Acute renal inflammatory injury can be prevented much more effectively by combination therapy than conventional therapy. This process is probably due to the prevention of free oxygen radical generation by anti-oxidants and inhibition of chemotaxis by selective cyclooxygenase-2 inhibitors.

Vasopressin and Epinephrine vs. Epinephrine Alone in Cardiopulmonary Resuscitation

During the administration of advanced cardiac life support for resuscitation from cardiac arrest, a combination of vasopressin and epinephrine may be more effective than epinephrine or vasopressin alone, but evidence is insufficient to make clinical recommendations. In a multicenter study, we randomly assigned adults with out-of-hospital cardiac arrest to receive successive injections of either 1 mg of epinephrine and 40 IU of vasopressin or 1 mg of epinephrine and saline placebo, followed by administration of the same combination of study drugs if spontaneous circulation was not restored and subsequently by additional epinephrine if needed. The primary end point was survival to hospital admission; the secondary end points were return of spontaneous circulation, survival to hospital discharge, good neurologic recovery, and 1-year survival. A total of 1442 patients were assigned to receive a combination of epinephrine and vasopressin, and 1452 to receive epinephrine alone. The treatment groups had similar baseline characteristics except that there were more men in the group receiving combination therapy than in the group receiving epinephrine alone (P=0.03). There were no significant differences between the combination-therapy and the epinephrine-only groups in survival to hospital admission (20.7% vs. 21.3%; relative risk of death, 1.01; 95% confidence interval [CI], 0.97 to 1.05), return of spontaneous circulation (28.6% vs. 29.5%; relative risk, 1.01; 95% CI, 0.97 to 1.06), survival to hospital discharge (1.7% vs. 2.3%; relative risk, 1.01; 95% CI, 1.00 to 1.02), 1-year survival (1.3% vs. 2.1%; relative risk, 1.01; 95% CI, 1.00 to 1.02), or good neurologic recovery at hospital discharge (37.5% vs. 51.5%; relative risk, 1.29; 95% CI, 0.81 to 2.06). As compared with epinephrine alone, the combination of vasopressin and epinephrine during advanced cardiac life support for out-of-hospital cardiac arrest does not improve outcome. (ClinicalTrials.gov number, NCT00127907.)

A 3-Year Follow-Up of All-Trans Retinoic Acid (ATRA) and Arsenic Trioxide (As2O3) as Front Line Therapy for Newly Diagnosed Acute Promyelocytic Leukemia (APL).

PURPOSE: To confirm the potential benefit of front-line use of all-trans retinoic acid (ATRA) combined with arsenic trioxide (As2O3) in patients with newly diagnosed acute promyelocytic leukemia (APL) with prolonged follow-up to median of 3-year and compared with historical control.PATIENTS AND METHODS: Two groups of newly diagnosed patients with APL were included in the analysis. The study group received combination therapy of ATRA and As2O3 includes 56 patients since April 2001. The historical control groups included 56 patients from May 1998 to March 2001. No statistically significant differences of clinical characteristics such as sex, age and hematological data were documented between two groups. For the study group groups, all patients received 25mg/m2 ATRA orally and 0.16mg/kg As2O3 intravenously per day till CR. Once CR achieved, they were given 3 courses of consolidation chemotherapy and then 5 cycles of sequential treatment of ATRA, As2O3 and 6-MP/MTX. For the historical group, the induction therapy was ATRA given at 25mg/m2 daily till CR and chemotherapy was added in case of leukocytosis. The post-remission therapy consists of chemotherapy with ATRA.RESULT: In study group, 52 (92.9%) patients achieved CR and the time to CR was 26.4±4.5 days. At last follow-up at February 2005, only two patients underwent extramedullary relapse and one died from CNS leukemia while all other patients were alive and remained in hematological remission. With a median follow-up of 34 months (21 to 46 months), the 3-year OS and EFS were estimated as 97.4% and 93.5%. For the historical control groups, the median follow-up was 56 months (12 to 79 months). The 3-year estimated OS and EFS was 83.2% and 57.7% (P=0.069 and 0.00001 respectively). Of notice, in the last follow-up, all evaluable patients in clinical remission maintained a complete molecular response (undetectable PML-RARa via both regular and real-time RT-PCR).CONCLUSION: Our 3-year follow-up data demonstrate a solid clinical benefit of front-line combination of ATRA and As2O3 in terms of EFS. There was also a trend toward improvement in OS which might translate into better chance of curing the disease.

Antihypertensive Efficacy and Tolerability of Two Fixed-Dose Combinations of Valsartan and Hydrochlorothiazide Compared with Valsartan Monotherapy in Patients with Stage 2 or 3 Systolic Hypertension: An 8-Week, Randomized, Double-Blind, Parallel-Group Trial

Combination therapy with at least 2 antihypertensive agents is usually needed to achieve appropriate blood pressure (BP) control in patients with isolated or predominant systolic hypertension. A currently recommended combination is a diuretic added to an angiotensin-receptor blocker. This was a study of the effects on sitting systolic BP (SBP)of 2 combinations of valsartan and hydrochlorothiazide (HCTZ) compared with valsartan monotherapy in patients with stage 2 or 3 systolic hypertension (SBP > or =160 mm Hg and < or =200 mm Hg) with or without other cardiovascular risk factors. After a placebo run-in period, patients were randomized to receive double-blind treatment with either valsartan 80 mg OD(monotherapy group) or valsartan 160 mg OD (combination-therapy groups) for 4 weeks, followed by forced titration to valsartan 160 mg OD (V160), valsartan 160 mg plus HCTZ 12.5 mg OD (V160 +HCTZ12.5), or valsartan 160 mg plus HCTZ 25 mg OD (V160 +HCTZ25) for an additional 4 weeks. End points were the change in SBP between the groups receiving combination therapy and the monotherapy group, between-group changes in diastolic BP (DBP), responder rates (SBP <140 mm Hg or a reduction in SBP of > or =20 mm Hg), and tolerability. A total of 774 patients were randomized to treatment: 261 to V160, 258 to V160+HCTZ12.5, and 255 to V160 +HCTZ25. The intent-to-treat population consisted of 767 patients (411 men, 356 women; mean age, 60 years; mean weight, 84 kg; clinic mean [SD] baseline BP, 167.5 [8.1]/93.4 [9.1] mm Hg). All treatments produced significant reductions in SBP from baseline (mean [SD] reduction, 20.7 [15.7] mm Hg with V160, 27.9 [13.8] mm Hg with V160 +HCTZ12.5, and 28.3 [13.1] mm Hg with V160+HCTZ25; all, P < 0.05). DBP was reduced by 6.6 (8.9) mm Hg in the V160 group and by 10.2 (7.7) and 10.1 (7.8) mm Hg in the V160+HCTZ12.5 and V160 +HCTZ25 groups, respectively (all, P < 0.05). The additional reductions in BP with V160+HCTZ25 did not reach statistical significance compared with V160+HCTZ12.5. Responder rates were 56.9% in the V160 group, 74.4% in the V160+HCTZ12.5 group, and 75.0% in the V160 +HCTZ25 group P < 0.05, combination therapy vs monotherapy). Adverse events were reported by 27.5% of patients in the monotherapy group, compared with 28.6% and 34.0% in the groups that received V160+HCTZ12.5 and V160+HCTZ25, respectively; the differences were not significant between treatment groups. Monotherapy with V160 was effective in these patients with stage 2 or 3 systolic hypertension. Significant additional reductions in SBP and DBP and an increase in responder rates were achieved with the addition to V160 of HCTZ12.5 and HCTZ25, with no significant effect on tolerability.

Additional treatments and reimbursement rates associated with prostate cancer treatment for patients undergoing radical prostatectomy, interstitial brachytherapy, and external beam radiotherapy

Objectives. To define patterns of treatment among contemporary patients undergoing radical prostatectomy, interstitial radiation, and external beam radiation for prostate cancer. Methods. We analyzed 291 consecutive patients (Stage T1-T3NXM0) who underwent definitive local treatment for prostate cancer with radical prostatectomy, interstitial seed implantation, or external beam radiation. Patients were stratified into three risk groups based on clinical T stage, serum prostate-specific antigen level at diagnosis, and biopsy Gleason score. The frequency of additional treatments, including androgen deprivation and external beam radiation, given within 3 months of initial local therapy was assessed. Patterns of care were compared and adjusted for risk. Results. Of the 291 patients, 107 (36.8%) underwent radical prostatectomy, 94 (32.3%) underwent interstitial seed implantation, and 90 (30.9%) underwent external beam radiation. Use of combination therapy differed significantly according to the type of initial local treatment and risk category. No patient in the low-risk group received combination therapy. For patients in the intermediate and high-risk groups, the frequency of combination therapy was significantly lower in the radical prostatectomy group when compared with either the interstitial seed implantation ( P <0.001 and P <0.02, respectively) or external beam radiation group ( P <0.001 and P <0.001, respectively). Conclusions. There are significant differences in resource utilization for contemporary patients undergoing definitive local therapy for prostate cancer. These differences may have a significant effect on treatment cost and morbidity, and they will likely make short-term comparisons between different treatment modalities difficult because of the high use of androgen deprivation in men treated with radiation therapy.

Interferon-α plus ribavirin in chronic hepatitis C resistant to previous interferon-α course: results of a randomized multicenter trial

Background/Aims: Interferon-α plus ribavirin seem to be more efficacious than interferon monotherapy in chronic hepatitis C. In a multicenter randomized trial, we evaluated the efficacy of this association for interferon-α resistant chronic hepatitis C. Methods: Fifty patients who were non-responders to recombinant or lymphoblastoid interferon-α were randomized to receive either ribavirin (800 mg/day) plus leucocytic interferon-α (3 mega units thrice weekly) or the same dose of interferon-α alone, for 6 months. Effects of therapy were evaluated by serum aminotransferase and hepatitis C virus RNA levels and control liver biopsies. Results: At the end of treatment, aminotransferase levels become normal in 9/26 patients receiving combination therapy (35% [confidence interval, 16% to 53%]) and in 2/24 receiving interferon-α alone (8% [confidence interval, −3% to 19%]) ( p=0.03). Aminotransferase normalization was never associated with hepatitis C virus RNA clearance. All patients with normal aminotransferase relapsed after discontinuation of therapy. At the end of treatment, mean hepatitis C virus RNA levels significantly decreased only in the group receiving combination therapy, but returned to pretreatment values 6 months thereafter. No histological improvement was observed in either group. Conclusions: There is no indication for treatment with interferon-α at the dose of 3 mega units thrice weekly plus 800 mg/day of ribavirin for 6 months in chronic hepatitis C resistant to interferon-α.

Effect of Levamisole on the Immune Response of Patients with Schistosomiasis after Treatment with Praziquantel

Successful therapy with praziquantel in schistosomiasis is dependent on a normal host immune system, i.e. the recognition of parasite antigen, to be effective in eradicating the parasite. Levamisole, a nonspecific immunomodulator, has been hypothesised to normalise deficient cell-mediated immunity. The aim of this study was to investigate the effect of levamisole on the immune response seen after presumed curative doses of praziquantel. After ethical approval, 29 male volunteers infected with Schistosoma haematobium were recruited and randomised to receive orally either (a) levamisole 5 mg/kg for 2 consecutive days, plus praziquantel 40 mg/kg as a single dose, (b) levamisole 5 mg/kg for 2 days, or (c) praziquantel 40 mg/kg as a single dose. Blood samples were collected on day 0 and again 3 months later for differential counts and specific IgG and IgE to whole-worm-antigen, as well as for the detection of eosinophil cationic protein (ECP). Levamisole treatment alone resulted in a significant drop in circulating eosinophil counts, i.e. a median (95% confidence interval) drop of 6.0 (1;7)%. Eosinophil counts did not change significantly after praziquantel therapy alone. ECP values were significantly reduced with levamisole alone and praziquantel alone, i.e. respective median (95% confidence interval) drops of 33.58 (18.94; 55.9) and 16.54 (3.6; 33.5) microg/L (p < 0.05). The group receiving combination therapy demonstrated significant increases in specific IgG values (p = 0.02) with no decline in ECP levels and eosinophil counts compared with baseline values. Levamisole alone had no effect on egg counts. In conclusion, levamisole inhibited circulating eosinophils and eosinophil activation when given alone, but caused immune stimulation when combined with praziquantel. The exact mechanism of action still needs to be determined.

The effects of UVB plus calcipotriol on systemic calcium homeostasis in patients with chronic plaque psoriasis

We studied the effects of combining topical calcipotriol, used at the maximal licensed dose, and narrow-band short wave ultraviolet light (TL01) on systemic calcium homeostasis in the treatment of chronic plaque psoriasis. Patients were randomized in an open fashion to receive either UVB alone, UVB plus 100 g of calcipotriol (50 micrograms/g) ointment per week or calcipotriol ointment alone (100 g/week). With the exception of a slight increase in serum phosphate in the group receiving combination therapy (from 0.92 to 1.22 mmol/l; P = 0.046), no differences were observed between or within the groups. Psoriasis area and severity scores (PASI) improved to a greater extent in those patients receiving both UVB and calcipotriol (P = 0.045). The combination of UVB and calcipotriol is a safe, effective treatment for chronic plaque psoriasis.

Reduction of restenosis after angioplasty in an atheromatous rabbit model by suicide gene therapy.

Gene delivery of the thymidine kinase (tk) gene combined with ganciclovir (GCV) limits intimal hyperplasia after abrasion of normal arteries. However, the low efficiency of adenoviral-mediated gene transfer to atherosclerotic arteries has raised concerns about the applicability of this strategy to the prevention of restenosis. A replication-defective adenoviral vector expressing tk (Ad-RSVtk) demonstrated selective toxicity toward GCV-treated arterial smooth muscle cells, with oligonucleolytic cleavage suggesting apoptosis. In vivo, after demonstration of tk expression after Ad-RSVtk delivery, the combination of Ad-RSVtk followed by GCV was tested in a rabbit model of angioplasty of atheromatous iliac arteries. Angioplasty (8 atm, 20 minutes) was performed by use of a hydrogel balloon coated with Ad-RSVtk (4x10(9) plaque forming units). GCV was infused (25 mg.kg(-1) I.V. BID) from days 2 through 7 after angioplasty in 8 of 12 rabbits. Four weeks later, morphometric analysis demonstrated a reduced intima-to-media ratio in the group receiving combination therapy compared with Ad-RSVtk alone (3.0+/-1.2 versus 5.2+/-0.5, P<.018). GCV per se had no effect on intimal hyperplasia after arterial injury. In vitro, Ad-RSVtk demonstrates selective toxicity toward GCV-treated arterial smooth muscle cells involving apoptosis. In vivo, GCV conditions reduction of neointimal formation after percutaneous delivery of Ad-RSVtk during angioplasty of atheromatous arteries.

Beneficial effect of combination hormonal therapy administered prior and following external beam radiation therapy in localized prostate cancer

Purpose : The aim of the present study isto investigate whether combined androgen blockade associated with radiation therapy for localized prostate cancer decreases at 12 and 24 months the rate of ppsitive follow-up biopsies and serum PSA compared to radiation therapy alone. This is the report of an interim analysis. Methods and Materials : One hundred and twenty patients with clinical Stage B1-T2a, B2-T2b/T2c, and C-T3/ T4, adenocarcinoma of the prostate were entered in a prospective randomized study. After written informed consent, the subjects were randomly allocated between external beam radiation therapy (EBRT) alone (group 1), 3 months of neoadjuvant combination therapy (LHRH-agnist + Flutamide) prior to EBRT (group 2), and a third group receiving combination therapy 3 months before, during, and 6 months after EBRT. There is no significant difference between the three groups concerning age, stage of disease, grade of tumor, and pretreatment PSA levels. Control transrectal ultrasound (TRUS)-guided needle biopsies (one core was taken from the initial cancer site regardlss of the presence or absence of TRUS abnormalities) were done 12 and 24 months after the end of EBRT. Serum PSA measurements were done on schedule visits. Results : Ninety-two and 68 patients underwent biopsies at 12 and 2 months, respectively, after the end of radiation therapy. While 62% of control patients at 12 months in Group 1 discloed residual neoplasm, only 30 and 4% showed residual disease in groups 2 and 3, respectively ( p = 0.0005). When looking at 24 months, 65, 28, and 5% showed residual cancer for groups 1, 2, and 3, respectively ( p = 0.00001). The PSA measurements indicate also at 12 months a difference between the three groups ( p < 0.0001), except at 24 monts, the difference between the group 2 and 3 is no longer significant. Conclusion : The preliminary analysis of this clinical trial indicates that patients treated with radiation therapy alone show a significantly higher rate of positive biopsies at 12 and 24 months after the end of radiation therapy as compared with those treated with total antiandrogen blockade (TAB) and radiation therapy. When analyzing the median PSA serum levels, we found the same advantage at 12 mnths, but, at the time of the analysis at 24 months, the PSA levels are not different between groups 2 and 3.

Total Ischaemic Burden European Trial (TIBET): Effects of ischaemia and treatment with atenolol, nifedipine SR and their combination on outcome in patients with chronic stable angina

To study the relationship between presence or absence of ischaemic events on Holter monitoring and occurrence of a hard or hard+soft endpoint. A randomized double-blind parallel group study of atenolol, nifedipine and their combination, with ambulatory monitoring off-treatment and after 6 weeks of randomized treatment and prospective follow-up of 2 years on average. Europe. 682 men and women with a diagnosis of chronic stable angina and who were not being considered for surgery. Hard endpoints were cardiac death, nonfatal myocardial infarction and unstable angina; soft endpoints were coronary artery bypass surgery, coronary angioplasty and treatment failure. The study showed no evidence of an association between the presence, frequency or total duration of ischaemic events on Holter monitoring, either on or off treatment, and the main outcome measures. There was a non-significant trend to a lower rate of hard endpoints in the group receiving combination therapy. Compliance, as measured by withdrawal from trial medication, was clearly poorest in the nifedipine group with similar withdrawal rates in the atenolol and combination therapy groups. The recording of ischaemic events in 48 h Holter monitoring failed to predict hard or hard+soft endpoints in patients with chronic stable angina.

Synergy between cilofungin and amphotericin B in a murine model of candidiasis

The efficacies of cilofungin and amphotericin B separately and together in mice with disseminated candidiasis were studied. Male CD-1 mice (age, 5 weeks) were infected intravenously with 3 X 10(5) CFU of Candida albicans. At 4 days postinfection, intraperitoneal therapy was initiated and was continued for 14 days. Therapy groups included those given cilofungin at 6.25 or 62.5 mg/kg/day (given twice daily), amphotericin B at 0.625 mg/kg/day (given once daily), cilofungin at 6.25 mg/kg/day plus amphotericin B, and cilofungin at 62.5 mg/kg/day plus amphotericin B. Mice were observed through 30 days postinfection. All infected untreated mice died of infection between days 6 and 18. Eighty-five percent of mice receiving cilofungin at 6.25 mg/kg/day died between days 13 and 30. All other mice survived. Quantitative determination of the number of CFU of C. albicans in the spleens and kidneys of all survivors revealed that mice that had received both drugs had lower residual burdens of C. albicans. All mice treated with cilofungin at 62.5 mg/kg/day plus amphotericin B had sterile spleens, whereas 42 to 58% of mice given cilofungin or amphotericin B monotherapy had sterile spleens. All kidneys were infected in mice which had received cilofungin at 62.5 mg/kg/day or amphotericin B. Neither organ was infected in 17% of each group receiving combination therapy with cilofungin and amphotericin B. The number of CFU in the kidneys of mice treated with cilofungin at 62.5 mg/kg/day plus amphotericin B was lower than those cultured from mice treated with cilofungin at 62.5 mg/kg/day (P less than 0.001, Mann-Whitney) or amhotericin B (P less than 0.05). Modest synergy was noted in inhibition of the C. albicans isolate in vitro. Pharmacokinetic studies showed elevated levels of cilofungin but not amphotericin B in sera of mice treated with combined therapy compared with those in mice given monotherapy. No overt toxicity was evident with any regimen. The mechanism of increased efficacy may be altered cilofungin distribution, excretion, or metabolism; antifungal synergy; or both. These results indicate that concurrent cilofungin-amphotericin B therapy has synergistic or additive efficacy in vivo.

Determination of bone and fat concentrations following systemic cefamandole and regional cefuroxime administration in patients undergoing knee arthroplasty

The effect of human urinary colony-stimulating factor (CSF-HU) on in-vitro phagocytosis of Legionella pneumophila, superoxide anion production and intracellular killing of Legion, pneumophila by guinea pig alveolar macrophages was studied. Alveolar macrophages when incubated with CSF-HU demonstrated enhanced phagocytic activity and superoxide production. The bactericidal activity of treated cells was enhanced when they were afterwards incubated with a low concentration of bacteria, but these cells failed to inhibit bacterial multiplication when they were incubated with bacteria in a 1:10 ratio. In vivo, an increase in the total peripheral leucocyte count in guinea pigs after intraperitoneal injection of CSF-HU occurred and this was accompanied by an increase in granulocyte and monocyte counts. A comparison of treatment of experimental Legion, pneumophila pneumonia with CSF-HU alone, ceftazidime alone and a combination revealed lower mortality rates in the group receiving combination therapy. These data suggest a possible function for CSF-HU of enhancing antibiotic therapy in Legionnaires' disease.

Carbohydrate and lipid metabolism in Turner syndrome: Effect of therapy with growth hormone, oxandrolone, and a combination of both

To evaluate the effects of growth-promoting therapy on carbohydrate metabolism in girls with Turner syndrome, we determined glucose and insulin concentrations during oral glucose tolerance tests (OGTTs) at baseline and after 5 days, 2 months, and 12 months of treatment with growth hormone (GH), oxandrolone, or a combination of GH and oxandrolone, or after the same intervals with no therapy. Before therapy, subjects had a significantly greater glucose response during OGTT than published normal control values. There were no significant changes in mean fasting glucose, cholesterol, or triglyceride concentrations in any of the treatment groups. The integrated glucose concentrations rose significantly over baseline values in the oxandrolone group at 2 and 12 months and in the combination group at 5 days. There were significant increases in the mean integrated insulin concentrations at 2 and 12 months for the group receiving oxandrolone alone and at all three times for the group receiving combination therapy. Thus oxandrolone, alone or in combination with GH, had significant effects on carbohydrate metabolism in subjects with Turner syndrome, whereas GH alone did not.

The management of moderately severe hypertension with cryptenamine and rauwolfia: Observations in patients treated for up to two years

1. (1) Cryptenamine (unitensen), an alkaloid of veratrum viride, was administered to 41 office patients with arterial hypertension of moderate severity for periods up to two years, by the oral route. The daily cryptenamine dose was distributed so that the medium dose was taken after breakfast, the minimum dose at 2 p.m., and the maximum dose at bedtime. 2. (2) Oral cryptenamine appeared to be a moderately potent antihypertensive agent when used as the sole mode of therapy on a long term basis. Sixty-eight per cent of the patients so treated reported no side reactions; in the remainder, gastrointestinal symptoms were mild and transitory. Emesis, previously reported as infrequent with cryptenamine therapy, occurred in one patient and was not a limiting factor in continuing treatment. 3. (3) The addition of reserpine, a rauwolfia alkaloid, to the basic cryptenamine therapy of 17 patients enhanced the depressor response to the latter and ameliorated side effects. In this group receiving combination therapy the most notable side-effect was a syndrome attributed to excessive loss of salt in the sweat during periods of high environmental heat and humidity. 4. (4) These data suggest that cryptenamine, alone or with reserpine, has value in the office management of the patient with arterial hypertension over prolonged periods. Clinical and laboratory observations appear to indicate that this therapy may be most effective in the hypertensive individual with cardiac and retinal area involvement and with relatively intact renal function.