Ram Groups Research Articles

Clinical outcomes of atezolizumab versus standard-of-care docetaxel with and without ramucirumab in patients with advanced non-small-cell lung cancer who received prior immunotherapy.

Atezolizumab is superior to docetaxel for patients with advanced non-small-cell lung cancer (NSCLC) who are pretreated with platinum-based chemotherapy based on the POPLAR and OAK trials. However, patients who received prior immunotherapy were excluded from these trials. The standard of care second-line therapy for these patients remains to be docetaxel with or without ramucirumab. The efficacy and safety of atezolizumab as a subsequent therapy in immunotherapy-pretreated patients are unknown. We conducted a retrospective study of all patients with locally advanced or metastatic NSCLC who were pretreated with immunotherapy at Mayo Clinic Jacksonville and Rochester from 2016 to 2022. Patients who received subsequent therapy of atezolizumab alone (Atezo), docetaxel (Doce), or docetaxel + ramucirumab (Doce+Ram) were included. In this cohort of 165 patients, 12.7% (n=21), 49.1% (n=81), and 38.2% (n=63) patients received subsequent Atezo, Doce, and Doce+Ram, respectively. 1-year landmark progression-free survival (PFS) were 23.8%, 6.2%, and 3.2% (p=0.006), and 2-year landmark PFS were 14.3%, 0%, and 0% (p<0.0001), in the Atezo, Doce, and Doce+Ram groups, respectively. About 20% patients with positive PD-L1 had durable response to atezolizumab. The Atezo group showed significantly greater overall survival (OS) improvement over Doce group (median OS 17.7 vs. 7.7 months, HR 0.47, 95% CI 0.29 - 0.76, p=0.008), and over Doce+Ram group (median OS 17.7 vs. 8.9 months, HR 0.55, 95% CI 0.32 - 0.95, p=0.047). 4 of 21 (19%) patients in the Atezo group developed immune-related adverse events (irAE). We observed statistically significant and clinically meaningful overall survival benefits of atezolizumab monotherapy compared with docetaxel +/- ramucirumab in patients with advanced NSCLC who were pretreated with immunotherapy. The survival benefit seems to be mainly from PD-L1 positive patients. Subsequent immunotherapy with Atezolizumab did not increase irAE rate.

RAM Cannula Versus Bi-Nasal Prongs as Respiratory Device Interfaces in Neonates of Thirty-Two or More Weeks of Gestation With Respiratory Distress: The First "ProRAM" Randomized Trial Report.

Using bilateral short nasal prongs as an interface for noninvasive respiratory support is challenging, and it is associated with nasal injury. We aimed to compare RAM cannula with nasal prongs in delivering noninvasive ventilation to newborn infants. This is a single-center randomized trial (trial registry: ISRCTN10561691). The setting involves a tertiary neonatal unit with a capacity of 30 beds and more than 13 years of experience in neonatal noninvasive ventilation. We included 50 infants born at ≥ 32 weeks of gestation, who had respiratory distress at birth. We excluded those with major congenital anomalies and those who required intubation in the delivery room. Primary outcomes were intubation rate and use of noninvasive positive-pressure ventilation (NIPPV); other outcomes included air leak and nasal injury rate. The infants were assigned using randomly generated numbers into bi-nasal prong and RAM canula groups in a 1:1 ratio. Two and four babies in the RAM and prong groups, respectively, were upgraded to NIPPV (P = 0.600). One versus no baby in the RAM vs. prong groups was intubated (P = 1.000). Newborns in the prong group required oxygen support for a longer period (mean duration: 154.6 ± 255.2 h) than those in the RAM group (40.7 ± 72.6 h, P = 0.030). None of the patients in the RAM group had traumatic nasal injury compared to five babies in the prong group (P = 0.050). Four babies in our study developed air leaks, with two in each group. The use of RAM cannula in delivering noninvasive ventilation to newborns ≥ 32 weeks of age did not affect the noninvasive ventilation failure rate or incidence of air leak. The use was associated with a shorter duration of respiratory support and a reduced risk of nasal septal injury.

Comparison of atezolizumab monotherapy to docetaxel with and without ramucirumab in patients with advanced non-small-cell lung cancer who received prior immunotherapy.

e21157 Background: Atezolizumab is superior to docetaxel for patients with advanced non-small-cell lung cancer (NSCLC) who are pretreated with platinum-based chemotherapy based on the POPLAR and OAK trials. However, patients who received prior immunotherapy (IO) were excluded from these trials. The preferred subsequent therapy for these patients remains to be docetaxel +/- ramucirumab. The efficacy and safety of atezolizumab as a subsequent therapy in IO-pretreated patients are unknown. Methods: We conducted a retrospective study of all patients with locally advanced/metastatic NSCLC who were pretreated with IO at Mayo Clinic Florida/Rochester in 2016 - 2022. Patients who received subsequent therapy of atezolizumab alone (Atezo), docetaxel (Doce), or docetaxel + ramucirumab (Doce+Ram) were included. Kaplan-Meier method and log-rank test were used for survival analysis. Results: Among 169 patients included, 51.5% were female, 91.7% were Caucasian. The median age was 67 (35 – 92). The histology was predominantly adenocarcinoma (76.3%). The most common metastatic sites were bone (51.5%), followed by CNS (44.4%). The median number of prior therapies was 2 (1 – 8). Pembrolizumab was the most used prior IO (87%), followed by durvalumab (10.7%) and nivolumab (8.3%). 13.6% (n = 23), 49.1% (n = 83), and 37.2% (n = 63) patients received subsequent Atezo, Doce, and Doce+Ram, respectively. PFS was improved in the Atezo group compared with Doce group (median PFS 3.9 vs. 3.7 months, HR 0.57, 95% CI 0.37 – 0.87, p = 0.015*). Notably, a prominent percentage of patients in the Atezo group appear to have long-term PFS benefits, demonstrated by 1-year PFS rates of 26.1%, 3.6%, and 4.8% (p = 0.003**), and 2-year PFS rates of 17.4%, 0%, and 0% (p = 0.002**), in the Atezo, Doce, and Doce+Ram groups, respectively. The median OS (months) in the Atezo, Doce, and Doce+Ram groups were 17.5, 7.6, and 11.5, respectively; and were 29.5, 7.2, and 6.9, respectively in the PD-L1 &gt; 50% subgroups. The Atezo group showed significantly greater OS improvement compared with the Doce group (HR 0.42, 95% CI 0.26 – 0.66, p = 0.001**). This benefit appears greater and remains statistically significant in the PD-L1 &gt; 1% (HR 0.39, 95% CI 0.22 – 0.71, p = 0.005**) and PD-L1 &gt; 50% (HR 0.37, 95% CI 0.15 – 0.91, p = 0.022*) subgroups. 5 of 23 (21.7%) patients in the Atezo group developed immune-related adverse events. 3 patients were grade 3 or 4. No grade 5 event. Conclusions: We observed statistically significant and clinically meaningful PFS and OS benefits of atezolizumab monotherapy compared with docetaxel in patients with advanced NSCLC who were pretreated with IO. The OS benefits of atezolizumab over docetaxel +/- ramucirumab was greater in PD-L1 &gt; 1% and PD-L1 &gt; 50% subgroups. Atezolizumab appears to be tolerable in IO-pretreated patients. These findings need to be verified in a prospective study.

Short-term outcomes of robot-assisted versus thoracoscopic-assisted Mckeown esophagectomy.

Thoracoscopic-assisted and robot-assisted Mckeown esophagectomy are currently two common surgical methods, but there is no clear statement on the advantages and disadvantages of the two. This study conducted a single-centre retrospective analysis of esophageal cancer patients diagnosed and treated at Lanzhou University Second Hospital from 1 February 2020 to 31 July 2022. According to the inclusion and exclusion criteria, 126 patients were finally included in the RAM group and 169 patients in the TAM group. There was no significant difference between the RAM and TAM groups in the number of lymph node dissections, operative time, the length of stay in the intensive care unit after surgery, the incidence of hoarseness, postoperative pulmonary complications, surgery-related complications, use of opioids after surgery, the length of postoperative hospital stay, and 30-day mortality. RAM is a minimally invasive alternative to TAM and has similar short-term oncological efficacy.

Effects of melatonin implants on reproductive performance of dairy sheep and dairy goats.

This study investigated the effects of melatonin implants in the female and male animals before the breeding season on the reproductive performance of Tahirova sheep and Turkish Saanen goats. Seventy-five sheep and 53 goats (including 6 rams and 4 bucks) were used in the research. Melatonin implants (18mg) were applied to half of the female and male animals, one to female animals and three to male animals. The rate of oestrus was determined as 100% in the melatonin (M) and control (C) groups. The non-return rate, conception rate and lambing rate were close in both groups of ewes and rams groups (p>.05). The rate of oestrus was 100% in the melatonin and control groups of does and bucks groups in Turkish Saanen goats. The non-return rate in does was 75.0±9.02% in M group and 92.0±5.53% in C group (p=.0101), the non-return rate was 83.3±6.92% in group M and 84.2±8.59% in group C for bucks (p=.5570). For ewes, the duration from ram introduction to first oestrus, conception and lambing was significantly lower in group M than in group C (p≤.05). Litter size of M in ewe and ram groups were 1.70±0.08 and 1.59±0.09, respectively, whereas it was 1.62±0.10 and 1.74±0.10 in C group, respectively. Birth weight significantly differed between ewe groups (p=.0017). For goats, the duration from buck introduction to first oestrus, conception and lambing was similar in the groups of does and bucks (p>.05). Litter size of M in doe and buck groups were 1.57±0.11 and 1.53±0.12, respectively, and 1.46±0.11and 1.50±0.09 in C group, respectively (p>.05). While the live weight and body condition score (BCS) of ewes were significantly affected by melatonin implants (p≤.05), the live weight and BCS of does were not affected. In conclusion, it might be said that melatonin implants obtained better results for reproduction in Tahirova sheep than Turkish Saanen goats.

Does advanced age affect reproductive variables, semen composition, and liquid semen storage during different seasons in Boujaâd rams?

The present research was conducted to evaluate the effects of season and age on scrotal circumference (SC), semen characteristics, semen composition, and sperm motility during liquid storage in Boujaâd rams. Semen was collected throughout 1 year from April 2014 to March 2015. Two ram groups, namely older rams including animals aged 5.5 to 6 years of age, and younger rams including animals aged 2.5 to 3 years of age were used. Scrotal circumferences, semen characteristics, and some biochemical variables from semen were measured. After collection and evaluation, the semen was extended in skim milk (SM) at 15 °C to a concentration of 0.8 × 109 spermatozoa/ml. Thereafter, samples were evaluated at different storage times (0, 8, and 24 h). The results indicate that older rams had greater values of SC, lesser semen quality, protein, lipid, and cholesterol concentrations than younger rams. Nevertheless, for both groups there were the least values for semen quality and semen composition in winter. The semen collected from younger rams had greater motility after liquid storage compared with that of the older rams. The least semen quality after liquid storage was recorded in the winter compared with the other seasons of the year for both age groups. In conclusion, results of the present study indicate that older Boujaâd sheep have lesser semen quality, different semen composition than younger rams after liquid storage and during different seasons of the year. Furthermore, there was a strong correlation between semen composition and motility of stored ram semen.

Certain behavioral characteristics and stress responses of out-of-breeding ewes and rams during an intensive fattening program

The aim was to investigate behaviors and stress responses of rams and ewes in an intensive fattening period. Out-of-breeding rams (Hemsin = 10, Karakul = 10) and ewes (Hemsin = 8, Karakul = 10) were used in the study. Sheep and rams belonging to each breed were placed into four different pens. Behavioral observations (individual, feeding, abnormal self-grooming behaviors) were performed 2 days a week for two groups a day for 1 h. Blood samples were collected at the beginning, at the 4th week, and at the end of the fattening period. Karakul ewes displayed significantly more feeding and rumination behavior than Hemsin ewes, while there was no significant difference between ram groups. Ewes displayed more lying and rumination behavior than rams in the current study. On the other hand, rams were more active than ewes and also showed more abnormal behavior (butting other animals) during the fattening period. Sheep breed had no influence on packed cell volume (PCV), hemoglobin (Hb) concentration, or cortisol level at any sampling time. PCV, Hb, and cortisol levels at the middle of the fattening period were higher in ewes than rams. In conclusion, the behavioral repertoire of Hemsin and Karakul breeds in intensive fattening does not reveal any stress responses.

Outcomes and Prognostic Factors of Cataract Surgery in Adult Extreme Microphthalmos With Axial Length

To study the long-term visual outcomes, complications, and prognostic factors for cataract surgery in extreme microphthalmos. Prospective cohort study. Thirty eyes with simple microphthalmos (11 eyes, axial length [AL] <18mm), complex microphthalmos (8 eyes, AL <18mm), and relative anterior microphthalmos (RAM; 11 eyes, corneal diameter [CD] <8mm) who underwent cataract surgery (phacoemulsification) in our hospital were followed for a mean of 25.3months with at least 3 visits at early (1day to 1week), mid (1-3months), and late (>6months) stages after surgery. The main outcome measures included the best-corrected visual acuity (BCVA), intraocular pressure (IOP), and complications. Significant improvements of BCVA were observed at the mid and late postoperative visits in the entire cohort when compared with preoperative value (P < .05). When eyes were divided into 3 groups, a statistically significant improvement in late-stage BCVA was observed in the simple microphthalmos and RAM groups. The AL, preoperative anterior chamber depth (ACD), and preoperative BCVA were significant prognostic factors for late-stage BCVA after surgery. The most common complications were early corneal edema (73%), glaucoma (33%), and posterior capsular opacification (23%). Preoperative ACD was significantly associated with the incidence of glaucoma after surgery (P < .05). Severe complications included suprachoroidal hemorrhage (3%), endothelial dysfunction (7%), and retinal detachment (7%). Cataract surgery provided visual improvement in extreme microphthalmos (simple microphthalmos and RAM), with higher risks of complications than with routine cataract surgeries. Extreme microphthalmos with preoperative characteristics of relatively longer AL, deeper ACD, and better BCVA may benefit more from cataract surgery.

The anti-osteoporosis effects of CSN1S2 protein of goat milk and yoghurt on a complete Freund's adjuvant-induced rheumatoid arthritis model in rats

This study aimed to evaluate the anti-osteoporosis effect of CSN1S2 protein from goat milk and yoghurt on a complete Freund's adjuvant (CFA)-induced rheumatoid arthritis (RA) model in rats. Twenty-four rats were randomly divided into six groups: control (untreated) group (C), group treated with CSN1S2 (CM) protein from goat milk, group treated with CSN1S2 protein from goat yoghurt (CY), RA group, RA group treated with CSN1S2 protein from goat milk (RAM), and RA group treated with goat yoghurt (RAY). Mineral elements and mesostructure were analyzed using X-ray fluorescence and scanning electron microscopy. Bone histomorphometry was analyzed using the BoneJ software. One way analysis of variance and Tukey post hoc tests were used to analyze and compare the means of all variables between groups. The phosphorus levels were not significantly different between treatment groups relative to the control group (p > 0.05), but were significantly higher in the CM and RAY groups relative to that observed in the CY group (p < 0.05). CSN1S2 protein of goat milk repaired the collagen structure in the femur trabecular bone. The trabecular thickness and volume were significantly lower in CM and CY groups relative to the control group (p < 0.05). The trabecular volume also decreased significantly in the CM group relative to the control group (p < 0.05). The trabecular thickness was significantly lower in the CY group relative to the CM group (p < 0.05), but the trabecular separation and trabecular volume were significantly greater (p < 0.05). The trabecular volumes were significantly elevated in the RAM and RAY groups relative to the CM group (p < 0.05). The trabecular thickness was significantly higher in the RAY group relative to the CM and CY groups (p < 0.05). CSN1S2 protein of goat milk is better than goat yoghurt in repairing femur crystallization and mesostructure in CFA-induced rheumatoid arthritis in rats.

Results Regarding Some Morphometric Features of Spermatozoa in Ram

It is well known nowadays that morphological type classification of spermatozoa is an important component of the modern semen evaluation. Meanwhile, current methods of analysis are subjective and highly diversified; they are also ones of the best tools for artificial insemination using cryogenic preserved semen for the contemporary livestock producer. The aim of the present study was to determine if there are differences associated with sperm head morphometric dimensions in individuals with different sexual maturity ratings. For the present results, there was setting off ram groups depending on age: 12, 36 and 72 months of age. There were used random images from fresh sperm and each head spermatozoon was measured with the aid of a specialized soft for four primary parameters (length, L; area, A; width, W and perimeter, P) and four derived parameters (ellipticity, L/W; rugosity, 4πA/P2; elongation, L–W/L+W and regularity, πLW/4A). The analyzed data were statistically processed, being recorded the main population parameters: the average, its error, the standard deviation, the coefficient of variability. There were no significant differences in the sperm head dimension or shape among middle-aged and old individuals (P > 0.05). However, significant differences were detected in area, perimeter and width (lower values) and length, ellipticity and elongation (higher values) in old or middle-aged individuals compared with young individuals (P < 0.01). As a conclusion, this study confirms that ram age is related to sperm morphometric size. Therefore, the present study provides information regarding the maturation of ram sperm and supports the idea that the dimensions of ram spermatozoa may be taken as an approximate indication of its relative maturity.

Seasonal reproductive performance of crossbred ewes in intensive lamb-production systems

The lambing performance of 1179 crossbred ewes with 5540 joining records in three seasons (autumn, winter and spring) at two sites (Cowra and Wagga Wagga) was evaluated in three lamb-production systems (spring joining with autumn backup matings at both locations, with accelerated lambing at Cowra or annual autumn joining at Wagga Wagga) over 4 years. Two genotypes of ewes, Border Leicester × Merino (BLM) and Hyfer (Dorset × Merino composite), were used at both sites, with natural matings to Dorset, Suffolk or Hyfer rams. The following five traits were analysed separately at each site to evaluate ewe lambing performance: fertility, litter size, lambs born (per ewe joined), lambs weaned (per ewe joined) and weight of lamb weaned (per ewe joined). The mixed model included fixed effects for season of joining, ewe breed, ram group, ewe prejoining weight (spline) and their interactions, with ewe fitted as a random effect. The autumn (February) joinings had higher ewe fertility, litter size and overall lamb production than did joinings in spring (October and November), with winter (June) being intermediate. At the autumn joinings, the BLM ewes had higher fertility, lambs weaned and weight of lamb weaned than did the Hyfer ewes, although this was reversed at the spring joinings, causing significant season × ewe breed interactions. While litter size was larger in the autumn than in the spring for both breeds there was a much smaller seasonal effect among the Hyfer than BLM ewes. Prejoining ewe weight had a significant effect on all reproduction traits, with generally a curvilinear response with increasing weight. The interactions of weight with season × ewe breed were significant (P &lt; 0.001) for all traits at Cowra and most traits at Wagga Wagga. Ram group was significant (P &lt; 0.05) for most traits, with ewes joined to Hyfer rams having higher fertility than those joined to Suffolk. and with Dorset rams being intermediate. At Wagga Wagga, this was the case for spring joinings, but there was no difference between the ram groups in autumn, causing a significant ram × season interaction (P &lt; 0.001). Ewe repeatability ranged from 0.15 to 0.25 for all traits. Using suitable breeds or genotypes, together with optimising management, could improve out-of-season lamb production.

Effect of ramipril on the electrophysiological characteristics of ventricular myocardium after myocardial infarction in rabbits

The current study aims to explore the effect of ramipril on the occurrence of ventricular arrhythmias and its possible mechanism after myocardial infarction (MI) in rabbits. A total of 24 rabbits were divided into three groups: the sham operation group (SHAM), the MI group, and the ramipril group (RAM). All groups were subjected to thoracotomy under sterile conditions; the MI and RAM groups underwent ligation of the left anterior descending coronary artery. On the second day after surgery, the RAM group was given ramipril (1 mg/kg per day). The rabbits in each group were fed for 12 weeks. The monophasic action potentials of the epicardium, mid-myocardium and endocardium in each group were, respectively, recorded before the MI and at 12 weeks after the MI. Meanwhile, the episodes of ventricular tachycardia or fibrillation (VT/VF) induced by procedure stimulations were counted, and the changes in L-type Ca flux (Ica-L) were recorded by means of the whole-cell patch-clamp technique. The episodes of VT/VF were decreased in the RAM group after MI. At 12 weeks after MI, the transmural dispersion of repolarization (TDR) in the MI group was prolonged significantly compared with the SHAM and RAM groups. The density of Ica-L in the MI group was significantly lower than that any other group. Ramipril manifestly decreases the incidence of VT/VF after MI in rabbits, and the mechanism may be associated with its inhibitory effect on electrical remodeling after MI.

Influence of feeding level on live body weight and semen characteristics of Sardinian rams reared under intensive conditions

The aim of the present study was to assess the effects feeding level on body weight changes and semen parameters in adult Sardinian rams reared under intensive conditions in a semi-arid area of southern Italy. During an experimental period of 90 days, 24 healthy Sardinian rams were divided into three equal groups that differed in their feeding level, in terms of concentrate amount. The control-concentrate (CC; n = 8) group received 1.0 times their maintenance requirements, the medium-concentrate (MC; n = 8) group received a diet that supplied 1.2 times their maintenance requirements, and high-concentrate (HC, n = 8) group received a diet that supplied 1.5 times their maintenance requirements. Mixed vetch-oat hay was offered ad libitum to ram groups and water and mineral licks were freely available. Body weight and feed intake was recorded weekly, and semen characteristics were determined every 2 weeks. Dietary treatment affected final body weight (P < 0.01) as feeding level increased. Total dry matter and protein intake changed significantly (P < 0.05 and P < 0.01, respectively) among experimental groups. Semen volume and concentration were positively influenced by feeding level for HC group, whereas no differences were observed in sperm viability and scrotal circumference of rams. It was concluded that dietary level with higher concentrate supplementation resulted in improved body weight gain, feed intake, sperm production, and semen quality in Sardinian rams.

Impact of Quadruple Regimen of Clarithromycin Added to Metronidazole‐Containing Triple Therapy AgainstHelicobacter pyloriInfection Following Clarithromycin‐Containing Triple‐Therapy Failure

The establishment of an optimal second-line regimen for Helicobacter pylori infection is required. Although quadruple therapy should overcome resistance to either clarithromycin or metronidazole, the effects of a quadruple regimen in second-line therapy are unknown. This study aims to evaluate the efficacy of triple therapy composed of proton pump inhibitor/amoxicillin plus metronidazole with the combined additive effects of clarithromycin as a second-line quadruple therapy against H. pylori infection. Participants were 104 patients in whom first-line therapy containing proton pump inhibitor-amoxicillin-clarithromycin failed. Before starting second-line therapy, patients underwent endoscopy to obtain H. pylori strain for antibiotic susceptibility tests. Patients were randomized to receive rabeprazole (10 mg), amoxicillin (750 mg), and metronidazole (250 mg), either with clarithromycin (200 mg; RAMC group) or without (RAM group); all treatments were administered twice daily for 7 days. H. pylori eradication was confirmed by (13)C-urea breath tests performed 2 to 3 months post-therapy. As shown by intention-to-treat/per-protocol analyses, the cure rates for H. pylori infection were 88.5%/93.9% and 82.7%/84.3% for the RAMC and RAM groups. Although the study probably had an insufficient power to show a significant difference between the cure rates of the two regimens, the eradication rates showed a clear trend in favor of the RAMC group. There were no severe side-effects in any group. In Japan, the RAMC regimen is thought to be a promising alternative strategy for second-line eradication of H. pylori infection.

Moxifloxacine Plus Amoxicillin and Ranitidine Bismuth Citrate or Esomeprazole Triple Therapies for Helicobacter pylori Infection

Up to 20% of patients, or even more, will fail to obtain eradication after a standard triple therapy. The aim of this study is to evaluate the efficacy of moxifloxacine-containing regimens in the first-line treatment of Helicobacter pylori. One hundred and twenty H. pylori-positive patients were randomized into four groups to receive one of the following 14-day treatments: ranitidine bismuth citrate (RBC) 400 mg b.d. plus amoxicillin 1 g b.d. and clarithromycin 500 mg b.d. (RAC group, n = 30); RBC 400 mg b.d. plus moxifloxacine 400 mg o.d. and amoxicillin 1,000 mg b.d. (RAM group, n = 30); esomeprazole 40 mg b.d. plus amoxicillin 1,000 mg b.d. plus clarithromycin 500 mg b.d. (EAC group, n = 30); and esomeprazole 40 mg b.d. plus amoxicillin 1,000 mg b.d. plus moxifloxacine 400 mg o.d. (EAM group, n = 30). Eradication was assessed by (13)C urea breath test 8 weeks after therapy. Per-protocol and intention-to-treat eradication was achieved in 23 out of 30 patients (76.7%, 95% confidence interval [CI]: 61-92) in the RAC group, in 20 patients (66.7%, 95% CI: 49-84) in the RAM group, in 16 patients in the EAM group (53.3%, 95% CI: 34-71), and in 19 patients in the EAC group (63.3%, 95% CI: 54-72). Mild or moderate side-effects were significantly more common in the EAM group (70%) compared to the RAC (36.6%), RAM (43.3%), and EAC (56.6%) groups (P = 0.03). From our results, we conclude that moxifloxacine-containing triple therapies have neither eradication nor compliance advantages over standard triple therapies. Further studies with new antibiotic associations are needed for the better eradication of H. pylori in developing regions of the world.

ECOLOGY OF GASTROPOD AND BIGHORN SHEEP HOSTS OF LUNGWORM ON ISOLATED, SEMIARID MOUNTAIN RANGES IN UTAH, USA

Isolated, nonmigratory populations of bighorn sheep (Ovis canadensis) may experience high exposure to lungworms (Protostrongylus spp.) through a build-up of fecal material. However, semiarid climates may hinder lungworm transmission by limiting terrestrial gastropods, the intermediate hosts. We assessed potential for lungworm transmission, documented occurrence of transmission, and identified habitat types where transmission was likely to occur on ranges of two recently introduced populations of bighorn sheep in northern Utah. Gastropods were collected weekly on Antelope Island and the Newfoundland Mountains, May-August 2001-02, from each of the four major habitat types (riparian, rock, desert shrub, and grass). Distribution of 113 bighorn sheep groups was observed, and 421 fecal pellet groups were collected to estimate lungworm levels. A total of 1,595 gastropods representing five genera were collected from both ranges. Vallonia made up 85% of all gastropods collected. Of 980 gastropods collected on Antelope Island in 2002, only Vallonia were found infected with protostrongylid-type larvae (10 of 980=1%). Lungworm prevalence in bighorn fecal samples was 97% on Antelope Island and 90% on the Newfoundland Mountains. Lungworm prevalence in lambs indicated lungworm transmission was occurring on Antelope Island. Lungworm transmission was likely occurring in riparian habitat due to abundant gastropods, presence of infected gastropods, and reliance by bighorn sheep on few water sources. Differences in spatial distribution between ram and nursery groups may partly explain higher fecal larvae counts in nursery than in ram groups. We suggest lungworm levels in bighorn sheep on semiarid ranges may increase in dry years as bighorn sheep concentrate use on fewer perennial water sources.

Sexual activity and puberty in pure Awassi and crosses and backcrosses with Charollais and Romanov sheep breeds

The aim of this experiment was to study sexual activity, scrotal circumference and the occurrence of puberty in five breed groups of ram lambs. Awassi (A, n = 8), F1 Charollais‐Awassi (CA, n = 5), backcrossed Awassi‐Charollais‐Awassi (ACA, n = 9), F1 Romanov‐Awassi (RA, n = 9) and backcrossed Awassi‐Romanov‐Awassi (ARA, n = 8) ram lambs were randomly selected at weaning to be used in this study. Sexual activity was observed weekly by introducing two oestrous ewes into each m ale group for a period of 20 min. At the time of first expressed sexual interest in females, body weights (BW) (P < 0.05) and scrotal circumferences (SC) (P < 0.001) differed among ram breed groups, while age and testosterone concentrations were similar. Weights at puberty were similar among the ram breed groups. Puberty, however, occurred earlier (P < 0.01) in CA, RA and ACA than in A and ARA ram lambs. At puberty, testosterone concentrations were similar while SC were greater (P < 0.01) in CA, ACA and RA than in ARA ram lambs. However, greater (P < 0.05) testosterone concentrations were observed in crossbred than in Awassi ram lambs throughout the study. Similarly, BW and SC were greater (P < 0.05) in CA, RA and ACA than in A and ARA ram lambs throughout the study. Results of the present study indicate that crossbreeding Awassi with Charollais and Romanov sheep breeds improved reproductive parameters in the F1 crosses and the backcrossed ACAmales compared with the ARA backcrosses and pure Awassi ram lambs. The fact that age differed among ram groups while BW at puberty did not, indicates that body weight is more important than age for puberty occurrence.

Addition of Pioglitazone and Ramipril to Intensive Insulin Therapy in Type 2 Diabetic Patients Improves Vascular Dysfunction by Different Mechanisms

We examined the relationship between glycemic control, vascular reactivity, and inflammation in type 2 diabetic subjects. Thirty subjects with type 2 diabetes were initiated on intensive insulin therapy (continuous subcutaneous insulin infusion [n = 12] or multiple daily injections [n = 18]) and then randomized to either pioglitazone (PIO group;45 mg/day), ramipril (RAM group; 10 mg/day), or placebo (PLC group) for 36 weeks. Euglycemic-hyperinsulinemic clamp was used to quantify insulin resistance, and plethysmography was used to assess changes in forearm blood flow (FBF) after 1) 5 min of reactive hyperemia and 2) brachial artery infusion of acetylcholine (7.5, 15, and 30 microg/min) and sodium nitroprusside (3 and 10 microg/min). The decreases in A1C (approximately 9.0-7.0%) and fasting plasma glucose (approximately 190-128 mg/dl) were equal in all groups. In the PIO group, glucose disposal increased from 3.1 to 4.7 mg x kg(-1) x min(-1), and there was a greater decrease in plasma triglycerides ( approximately 148 vs. 123 mg/dl) and free fatty acids (approximately 838 vs. 595 mEq/l) compared with the RAM or PLC groups (P < 0.05). Plasma adiponectin doubled with pioglitazone treatment (6.2 +/- 0.7 to 13.1 +/- 1.8 microg/ml), while endothelin-1 decreased only with ramipril treatment (2.5 +/- 0.2 to 1.1 +/- 0.2 pg/ml) (P < 001). The increase in FBF during reactive hyperemia (215%) and acetylcholine (from 132 to 205%, 216 to 262%, and 222 to 323%) was greater in the PIO versus RAM or PLC groups. In contrast, FBF during sodium nitroprusside treatment was greater in the RAM group (141-221% and 218-336%) compared with the PIO or PLC groups (all P < 0.05). Addition of pioglitazone or ramipril to intensive insulin therapy in type 2 diabetes further improves vascular dysfunction. Pioglitazone enhances endothelial-mediated vasodilation, whereas ACE inhibition enhances endothelial-independent vasodilation. These different vascular effects, combined with the observation that pioglitazone decreases free fatty acids and triglycerides and increases adiponectin, while ramipril reduces endothelin-1, suggest that different mechanisms underlie the vascular responses.

Comparison of efficacies of dual therapy and triple therapy using rabeprazole in second‐line eradication of Helicobacter pylori in Japan

SummaryBackgroundThe only authorized second‐line Helicobacter pylori regimen in Japan is proton pump inhibitor + amoxycillin + clarithromycin. However, it has been reported that this second‐line regimen is not effective. In this study, we evaluated the efficacy of dual and triple eradication therapies using rabeprazole as second‐line H. pylori eradication regimens.AimTo evaluate the efficacy of dual and triple eradication therapies using rabeprazole as second‐line H. pylori eradication therapy.MethodsSixty‐two H. pylori‐positive patients with first‐line eradication failure were randomly assigned to two groups. The RAM group was administered rabeprazole 20 mg + amoxycillin 1500 mg + metronidazole 500 mg daily for 1 week. The RA group was administered rabeprazole 40 mg + amoxycillin 2000 mg daily for 2 weeks. Eradication of H. pylori infection was determined by 13C‐urea breath testing at 8 weeks after completion of treatment. Prior to treatment, amoxycillin, clarithromycin and metronidazole susceptibility, and CYP2C19 phenotype status were determined.ResultsEradication rates for the RAM and RA groups were 97% and 74%, respectively. Eradication rates were not influenced by CYP2C19 phenotype in either group. Eradication rates for clarithromycin‐resistant patients were 100% in the RAM group and 77% in the RA group.ConclusionsOne week with RAM therapy and 2 weeks with RA therapy were effective as second‐line eradication therapy for H. pylori infection; moreover, RAM was more effective than RA therapy.

Comparison of efficacies of dual therapy and triple therapy using rabeprazole in second‐line eradication of Helicobacter pylori in Japan

SummaryBackgroundThe only authorized second‐line Helicobacter pylori regimen in Japan is proton pump inhibitor + amoxycillin + clarithromycin. However, it has been reported that this second‐line regimen is not effective. In this study, we evaluated the efficacy of dual and triple eradication therapies using rabeprazole as second‐line H. pylori eradication regimens.AimTo evaluate the efficacy of dual and triple eradication therapies using rabeprazole as second‐line H. pylori eradication therapy.MethodsSixty‐two H. pylori‐positive patients with first‐line eradication failure were randomly assigned to two groups. The RAM group was administered rabeprazole 20 mg + amoxycillin 1500 mg + metronidazole 500 mg daily for 1 week. The RA group was administered rabeprazole 40 mg + amoxycillin 2000 mg daily for 2 weeks. Eradication of H. pylori infection was determined by 13C‐urea breath testing at 8 weeks after completion of treatment. Prior to treatment, amoxycillin, clarithromycin and metronidazole susceptibility, and CYP2C19 phenotype status were determined.ResultsEradication rates for the RAM and RA groups were 97% and 74%, respectively. Eradication rates were not influenced by CYP2C19 phenotype in either group. Eradication rates for clarithromycin‐resistant patients were 100% in the RAM group and 77% in the RA group.ConclusionsOne week with RAM therapy and 2 weeks with RA therapy were effective as second‐line eradication therapy for H. pylori infection; moreover, RAM was more effective than RA therapy.