Foetal dwarfism in sheep—an effect of high atmospheric temperature during gestation

1958 ◽  
Vol 51 (1) ◽  
pp. 84-89 ◽  
Author(s):  
N. T. M. Yeates
Keyword(s):  
Birth Weight ◽  
Atmospheric Temperature ◽  
Long Bones ◽  
X Rays ◽  
Nutritional Effect ◽  
Group 3 ◽  
The Mean ◽  
Group 2 ◽  
Group 1

The course of pregnancy was followed in three groups of Peppin-strain Merino ewes. Group 1 of seven ewes, maintained on a high plane of nutrition, all lambed; the mean birth weight of lambs was 8 lb. 6 oz. The six ewes in group 2, kept on a low plane of nutrition, all lambed; the mean birth weight of their lambs was 1 lb. 9 oz. lower (P<0·01). The seven ewes in group 3 kept on a low plane of nutrition and subjected daily to temperatures of 112° F. dry bulb, 92° F. wet bulb, produced only four lambs; the mean birth weight was 4 lb. 6 oz. less than those from group 1, and 2 lb. 13 oz. less than those from group 2 (P < 0·001).Scale photographs of the lambs, and X-rays and measurements of their long bones, after dissection, showed that the lambs of group 3 were miniatures: their skeletons were much reduced in size, whereas low nutrition alone (group 2), caused little skeletal reduction.The mechanism of dwarfing is not clear. However, fore-cannon bone lengths and liver weights, considered in relation to lamb birth weights indicated that it was not a nutritional effect.This study was undertaken at the Physiology Department, University of Queensland. It is a pleasure to thank Prof. W. V. Macfarlane for the valuable facilities, and for his help and encouragement.

scholarly journals Association between serum oestradiol level on the hCG administration day and neonatal birthweight after IVF-ET among 3659 singleton live births

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yu Liu ◽  
Jing Li ◽  
Wanyu Zhang ◽  
Yihong Guo
Keyword(s):  
Birth Weight ◽  
Ovarian Stimulation ◽  
Group 4 ◽  
Group 6 ◽  
Group 3 ◽  
Group 5 ◽  
Group 2 ◽  
The Impact ◽  
Ivf Et ◽  
Group 1

AbstractOestradiol, an important hormone in follicular development and endometrial receptivity, is closely related to clinical outcomes of fresh in vitro fertilization-embryo transfer (IVF-ET) cycles. A supraphysiologic E2 level is inevitable during controlled ovarian hyper-stimulation (COH), and its effect on the outcome of IVF-ET is controversial. The aim of this retrospective study is to evaluate the association between elevated serum oestradiol (E2) levels on the day of human chorionic gonadotrophin (hCG) administration and neonatal birthweight after IVF-ET cycles. The data of 3659 infertile patients with fresh IVF-ET cycles were analysed retrospectively between August 2009 and February 2017 in First Hospital of Zhengzhou University. Patients were categorized by serum E2 levels on the day of hCG administration into six groups: group 1 (serum E2 levels ≤ 1000 pg/mL, n = 230), group 2 (serum E2 levels between 1001 and 2000 pg/mL, n = 524), group 3 (serum E2 levels between 2001 and 3000 pg/mL, n = 783), group 4 (serum E2 levels between 3001 and 4000 pg/mL, n = 721), group 5 (serum E2 levels between 4001 and 5000 pg/mL, n = 548 ), and group 6 (serum E2 levels > 5000 pg/mL, n = 852). Univariate linear regression was used to evaluate the independent correlation between each factor and outcome index. Multiple logistic regression was used to adjust for confounding factors. The LBW rates were as follows: 3.0% (group 1), 2.9% (group 2), 1.9% (group 3), 2.9% (group 4), 2.9% (group 5), and 2.0% (group 6) (P = 0.629), respectively. There were no statistically significant differences in the incidences of neonatal LBW among the six groups. We did not detect an association between peak serum E2 level during ovarian stimulation and neonatal birthweight after IVF-ET. The results of this retrospective cohort study showed that serum E2 peak levels during ovarian stimulation were not associated with birth weight during IVF cycles. In addition, no association was found between higher E2 levels and increased LBW risk. Our observations suggest that the hyper-oestrogenic milieu during COS does not seem to have adverse effects on the birthweight of offspring after IVF. Although this study provides some reference, the obstetric-related factors were not included due to historical reasons. The impact of the high estrogen environment during COS on the birth weight of IVF offspring still needs future research.

Comparison of the ATRIA, CHA2DS2-VASc, and Modified Scores ATRIA-HSV, CHA2DS2-VASc-HS, for the Prediction of Coronary Artery Disease Severity

Angiology ◽  
2021 ◽  
pp. 000331972199141
Author(s):  
Arafat Yildirim ◽  
Mehmet Kucukosmanoglu ◽  
Fethi Yavuz ◽  
Nermin Yildiz Koyunsever ◽  
Yusuf Cekici ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Vascular Disease ◽  
Operating Characteristics ◽  
Coronary Artery Disease Severity ◽  
Group 3 ◽  
The Mean ◽  
Group 2 ◽  
Artery Disease ◽  
Group 1

Many parameters included in the Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) and CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke, vascular disease, age 65-74 years, sex category) scores also predict coronary artery disease (CAD). We modified the ATRIA score (ATRIA-HSV) by adding hyperlipidemia, smoking, and vascular disease and also male sex instead of female. We evaluated whether the CHA2DS2-VASc, CHA2DS2-VASc-HS, ATRIA, and ATRIA-HSV scores predict severe CAD. Consecutive patients with coronary angiography were prospectively included. A ≥50% stenosis in ≥1epicardial coronary artery (CA) was defined as severe CAD. Patient with normal CA (n = 210) were defined as group 1, with <50% CA stenosis (n = 178) as group 2, and with ≥50% stenosis (n = 297) as group 3. The mean ATRIA, ATRIA-HSV, CHA2DS2-VASc, and CHA2DS2VASc-HS scores increased from group 1 to group 3. A correlation was found between the Synergy between PCI with Taxus and Cardiac Surgery score and ATRIA ( r = 0.570), ATRIA-HSV ( r = 0.614), CHA2DS2-VASc ( r = 0.428), and CHA2DS2-VASc-HS ( r = 0.500) scores ( Ps < .005). Pairwise comparisons of receiver operating characteristics curves showed that ATRIA-HSV (>3 area under curve [AUC]: 0.874) and ATRIA (>3, AUC: 0.854) have a better performance than CHA2DS2-VASc (>1, AUC: 0.746) and CHA2DS2-VASc-HS (>2, AUC: 0.769). In conclusion, the ATRIA and ATRIA-HSV scores are simple and may be useful to predict severe CAD.

scholarly journals Comparison of Changes in Number of Hyperreflective Dots After İntravitreal Ranibizumab or Dexamethasone İmplant in Patients with Branch Retinal Vein Occlusion

2021 ◽  
Author(s):  
Aylin Karalezli ◽  
Sema Kaderli ◽  
Ahmet Kaderli ◽  
Cansu Kaya ◽  
Sabahattin Sul
Keyword(s):  
First Year ◽  
Intravitreal Ranibizumab ◽  
Retinal Layers ◽  
Vein Occlusion ◽  
Significant Difference ◽  
Group 3 ◽  
The Mean ◽  
Group 2 ◽  
Group 1

Abstract Purpose: To compare the effect of intravitreal ranibizumab (IVR) or intravitreal dexamethasone implants (IVD) on regression of hyperreflective dots (HRDs) on optical coherence tomography (OCT) B-scan in patients with branch retinal vein occlusion (BRVO). Methods: 37 eyes of 37 patients with cystoid macular edema who received IVR or IVD and followed up for at least 12 months were included in this study. The patients were divided into three groups according to intravitreal treatment. Group 1 consisted of 12 eyes who received only IVD, group 2 consisted of 10 eyes who received only IVR on a pro re nata and group 3 consisted of 15 eyes who received both IVD and IVR. OCT parameters (CMT, number of HRDs, status of external limiting membrane (ELM) and ellipsoid zone (EZ)) and best-corrected visual acuity (BCVA) were compared between the groups over the follow-up time. HRDs were categorized as HRD in inner retinal layers (from the internal limiting membrane to the inner nuclear layer) or HRD in outer retinal layers (from the outer plexiform layer to the outer border of the photoreceptor layer).Results: There was no significant difference between groups in terms of BCVA, CMT, HRDs in the inner and the outer retinal layers at baseline visit. (p˃0.05 for all) Comparing the baseline values in all groups, a significant decrease was observed in CMT in the first year. (For group 1; p=0.013, group 2; p=0.010; group 3, p<0.001) The BCVA was significantly increased after 1 year in all groups. (p=0.001, p=0.006, p<0.001) The mean number of HRDs in inner and outer retinal layers were significantly decreased in group 1 and group 3. (For group 1; p<0.001, p=0.001, for group 3; p<0.001, p<0.001) However, there was no significant difference in terms of the mean number of HRDs in inner and outer retinal layers for group 2. (p=0.134, p=0.477) At the first year, the number of HRDs in inner and outer retinal layers was significantly lower in group 1 and group 3 than group 2. (For inner HRDs; group 1 vs. group 2 p=0.007, group 2 vs. group 3 p<0.001. For outer HRDs group 1 vs. group 2 p<0.001, group 2 vs. group 3 p<0.001.) The BCVA was higher in group 3 than group 2 at 1year. (p=0.048). There was no significant difference in terms of post-treatment CMT and the number of HRDs between group 1 and group3 in posthoc tests (p=0.621, p=0.876, and p=0.632).Conclusion: The reduction in HRDs at 12 months and better BCVA after IVD intimates that the HRDs should be considered as inflammatory markers in the follow-up of CME in BRVO. Thus, IVD injection could be more appropriate for patients with higher HRDs after BRVO.

scholarly journals Evaluation of Iron Status, Haemoglobin and Protein Levels of Pregnant Women in Owerri Metropolis

2021 ◽  
pp. 36-43
Author(s):  
I. L. Okoroiwu ◽  
Jane Ugochi Chinedu-Madu ◽  
Emmanuel Ifeanyi Obeagu ◽  
C. C. N. Vincent ◽  
O. M. T. B. Ochiabuto ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Serum Iron ◽  
Iron Deficiency Anaemia ◽  
Iron Status ◽  
Second Trimester ◽  
Protein Levels ◽  
Group 3 ◽  
The Mean ◽  
Group 2 ◽  
Group 1

The study was done to determine iron status, haemoglobin and protein levels of pregnant women in owerri metropolis. A total of 100 pregnant women were recruited for this study. The mean Hb levels in group 1, group 2, and group 3· were 12.00±1.68g/dl, 10.06±1.J4g/dl and 10.96±1.19g/dl respectively. The mean Serum ferritin level of group 1 was 67.00±88.38ng/ml, group 2, 52.48±52.47ng/ml and group 3, 51.26±48.70ng/ml. The mean Serum iron in group 1, 2 and 3 were 46.72±16.41 g/dl, 79.59±63.24 g/dl and 83.35±53.04 g/dl respectively. In group 1, 2 and 3 the mean results. ( g/dl) of TIBC were 295.58 ± 109.53, 324.06 ± 178.00 and 319.88 ± 92.95 and % T.S (%) were 18.78 ± 11.77,26.59 ± 19.40 and 17.97 ± 10.87 percent respectively. The mean total protein was group 1,6.83±l1.77g/dl, group 2,6.39±0.70g/dl and group 3, 6.39 ±0.98 g/dl while the mean albumin (g/dl) in group 1, 2 and 3 were 4.84±0.47, 4.13±0.28 and 4.14±0.29 respectively. The mean values of globulin (g/dl) were 1.98 ± 0.91, 2.29 ± 0.87 and 1.89 ± 0.90 in groups 1, 2 and 3 respectively. As gestational age increased; serum ferritin, total protein, and albumin levels decreased while serum" iron and TIBC increased. The differences in the mean results between the groups were statistically significant (p<0.05) while % T.S and globulin levels when compared showed no significant difference (p>0.05). Iron status showed no statistical difference with increasing parity (p>0.05). However, from this study iron deficiency anaemia was most prevalent in second trimester; hence iron status estimation should be an integral part of routine antenatal care test during second trimester of each pregnancy for proper assessment and management of iron deficiency anaemia in pregnancy.

scholarly journals Serum Bioavailable Testosterone: Assayed or Calculated?

2006 ◽  
Vol 52 (3) ◽  
pp. 474-481 ◽  
Author(s):  
Frank Giton ◽  
Jean Fiet ◽  
Jérôme Guéchot ◽  
Fidaa Ibrahim ◽  
Françoise Bronsard ◽  
...  
Keyword(s):  
Ammonium Sulfate ◽  
Association Constants ◽  
Sex Hormone Binding Globulin ◽  
Precipitation Method ◽  
Microsoft Excel ◽  
Bioavailable Testosterone ◽  
Group 3 ◽  
The Mean ◽  
Group 2 ◽  
Group 1

Abstract Background: Bioavailable testosterone (BT), circulating testosterone not bound to sex hormone–binding globulin (SHBG), is thought to easily penetrate cells. We compared BT measurements obtained by assays with those obtained by calculation with different testosterone association constants. Methods: We obtained sera from 2 groups of hypogonadal men [group 1 (G1), 1421 samples; group 2 (G2), 170 samples] and a group of healthy men [group 3 (G3), 109 samples]. We added minute doses of [3H]testosterone to the sera, precipitated the SHBG-bound fraction of testosterone with ammonium sulfate (50% saturation), and then assayed serum BT (ABT) as %BT × total. Calculated BT (CBT) was determined with theoretical association constants of testosterone for SHBG (Ks = 1 × 109 L/mol) and albumin (Ka = 3.6 × 104 L/mol) and paired optimal Ks and Ka values obtained by use of Microsoft Excel software. Results: CBT calculated with theoretical constants differed from ABT by &gt;30% in 85.7% (G1), 84.1% (G2), and 77.9% (G3) of samples, and the mean CBT/ABT ratios were 1.57 (G1), 1.85 (G2), and 1.50 (G3) in spite of fairly good correlations. CBT calculated with paired optimal Ks and Ka differed from ABT by &lt;30% in 87.4% (G1), 87.5% (G2), and 97.5% (G3) of samples, and mean CBT/ABT ratios were 0.95–1.04. Conclusions: To obtain CBT values as close as possible to ABT, optimal paired association constants determined for each studied population must be used instead of the theoretical association constants. Considering the uncertainty of calculating BT, however, use of the ammonium sulfate precipitation method for determining BT is advisable.

EVALUATION OF EFFICACY OF SILODOSIN VERSUS SILODOSIN WITH DEFLAZACORT IN EXPULSION OF LOWER URETERIC CALCULI

2021 ◽  
pp. 30-33
Author(s):  
Dev Yadav ◽  
P.N Agarwal ◽  
Sham Lal Singla ◽  
Kanwar Singh Goel ◽  
R. Talukdar ◽  
...  
Keyword(s):  
Plain Radiograph ◽  
Pharmacological Therapy ◽  
Urinary Stones ◽  
Controlled Study ◽  
Expulsion Rate ◽  
Ureteric Calculi ◽  
Group 3 ◽  
The Mean ◽  
Group 2 ◽  
Group 1

Objectives: To compare the efcacy of silodosin versus silodosin with deazacort in expulsion of lower end ureteric calculi, in terms of episodes of pain,stone expulsion rate,stone expulsion time ,analgesic requirements and side effects Introduction: Ureteric calculi represent 20% of urinary stones. Ureteroscopy and Shock wave lithotripsy proven the method of treatments for lower ureteric stones; however, they are expensive and not risk free. Aconservative approach is becoming more popular as a result of advances in pharmacological therapy which reduces the symptoms and helps in stone expulsion. We performed a randomized controlled prospective study to evaluate the efcacy of Deazacort in combination with alpha blocker silodosin in medical management of symptomatic lower Ureteric stones of ≤8 mm size. Material and methods: A prospective randomised controlled study was conducted on 60 patients, age ≥ 18 , who had unilateral lower ureteric stone of ≤ 8 mm. Patients were divided into three groups. Group 1 received silodosin 8 mg for 14 days,Group 2 received silodosin 8 mg plus deazacort 30mg daily for 14 days and Group 3 (control) received diclofenac potassium (75 mg ) when required. The patients were followed-up by ultrasonography ,plain radiograph KUB and computed tomography (in some cases). Results: There was a higher stone expulsion rate of 95% in Group 2 as compared to Group 1(85%) and Group 3(35%) . Group 2 showed a signicant advantage for stone expulsion time ,decreased pain episodes and analgesic use. Two patients, one in group 1 and group 2, reported retrograde ejaculation. Conclusion: The results showed that silodosin with deazacort , increases the stone expulsion rate, decrease the stone expulsion time, decreases the mean number of pain episodes and decreases the mean analgesic dosage requirement. But larger study is required to establish its efcacy for expulsion rate which will be statistically signicant.

Frameless ROSA® Robot-Assisted Lead Implantation for Deep Brain Stimulation: Technique and Accuracy

2019 ◽  
Vol 19 (1) ◽  
pp. 57-64 ◽  
Author(s):  
Lannie Liu ◽  
Sarah Giulia Mariani ◽  
Emmanuel De Schlichting ◽  
Sylvie Grand ◽  
Michel Lefranc ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Brain Stimulation ◽  
Ct Scans ◽  
X Rays ◽  
Robot Assisted ◽  
Lead Position ◽  
The Mean ◽  
Group 2 ◽  
Deep Brain ◽  
Group 1

Abstract BACKGROUND Frameless robotic-assisted surgery is an innovative technique for deep brain stimulation (DBS) that has not been assessed in a large cohort of patients. OBJECTIVE To evaluate accuracy of DBS lead placement using the ROSA® robot (Zimmer Biomet) and a frameless registration. METHODS All patients undergoing DBS surgery in our institution between 2012 and 2016 were prospectively included in an open label single-center study. Accuracy was evaluated by measuring the radial error (RE) of the first stylet implanted on each side and the RE of the final lead position at the target level. RE was measured on intraoperative telemetric X-rays (group 1), on intraoperative O-Arm® (Medtronic) computed tomography (CT) scans (group 2), and on postoperative CT scans or magnetic resonance imaging (MRI) in both groups. RESULTS Of 144 consecutive patients, 119 were eligible for final analysis (123 DBS; 186 stylets; 192 leads). In group 1 (76 patients), the mean RE of the stylet was 0.57 ± 0.02 mm, 0.72 ± 0.03 mm for DBS lead measured intraoperatively, and 0.88 ± 0.04 mm for DBS lead measured postoperatively on CT scans. In group 2 (43 patients), the mean RE of the stylet was 0.68 ± 0.05 mm, 0.75 ± 0.04 mm for DBS lead measured intraoperatively; 0.86 ± 0.05 mm and 1.10 ± 0.08 mm for lead measured postoperatively on CT scans and on MRI, respectively No statistical difference regarding the RE of the final lead position was found between the different intraoperative imaging modalities and postoperative CT scans in both groups. CONCLUSION Frameless ROSA® robot-assisted technique for DBS reached submillimeter accuracy. Intraoperative CT scans appeared to be reliable and sufficient to evaluate the final lead position.

scholarly journals Acute Phase Effect of Memantine Hydrochloride in Experimental Peripheral Nerve Injury

2019 ◽  
Vol 08 (02) ◽  
pp. 113-118
Author(s):  
Hakan AK ◽  
Iskender Samet Daltaban ◽  
Sevilay Vural
Keyword(s):  
Peripheral Nerve ◽  
Nerve Injury ◽  
Peripheral Nerve Injury ◽  
Group 4 ◽  
Tnf Α ◽  
Group 3 ◽  
The Mean ◽  
Cox 2 ◽  
Group 2 ◽  
Group 1

Abstract Aim In this experimental study, we aimed to investigate possible healing effects of memantine hydrochloride, an N-methyl-d-aspartate (NMDA) antagonist, with clinical, biochemical, and histopathologic methods on acute peripheral nerve injury (PNI). Material and Method Forty-eight adult Wistar albino rats were divided into four groups (n = 12). The groups were arranged as sham-operated group (group 1), acute compression model group (group 2), trauma + low-dose memantine group (group 3), and trauma + high-dose memantine group (group 4). Memantine was administered intraperitoneally for 7 days. Subjects were sacrificed after the measurement of the sciatic nerve function index (SNFI) on the eighth day. Cyclooxygenase 2 (COX-2) and tumor necrosis factor-α (TNF-α) levels were measured in nerve tissues. Histopathologic evaluation was performed by electron microscopy. Results The mean sciatic function index (SFI) scores of groups 1 to 4 were +3.27 (standard deviation [SD] ±4.66),–18.2 (SD = ±11.7),–8.5 (SD = ±7.5), and–2.5 (SD = ±9), respectively. The mean COX-2 values were 0.98 ng/mL (SD = ±0.51), 1.89 ng/mL (SD = ±0.22), 1.39 ng/mL (SD = ±0.36), and 1.35 ng/mL (SD = ±0.59), respectively. TNF-α values were 0.09 pg/mL (SD = ±0.23), 1 pg/mL (SD = ±0.96), 0.46 pg/mL (SD = ±0.55), and 0.48 pg/mL (SD = ±0.78), respectively. Group 1 showed normal histologic findings. Group 2 showed marked edema particularly in large-diameter myelins. Myelin configurations were detected in large myelinated axons in group 3. The number of mast cells in endoneurium was high in group 4. Conclusion The efficacy of memantine in the acute phase of PNI appears to be significant according to the SNFI and biochemical tests. However, histologic findings suggest that high doses of memantine have a negative effect on PNI.

scholarly journals Prediction of Ergogenic Mouthguard Effects in Volleyball: A Pilot Trial

2019 ◽  
Vol 03 (03) ◽  
pp. E96-E101
Author(s):  
Antina Schulze ◽  
Martin Busse
Keyword(s):  
Dynamic Balance ◽  
Pilot Trial ◽  
Dental Occlusion ◽  
Normal Range ◽  
Specific Test ◽  
Group 3 ◽  
The Mean ◽  
Group 2 ◽  
Resting Tone ◽  
Group 1

AbstractDental occlusion may affect static and dynamic balance. The effects of a mouthguard on pinpoint accuracy in volleyball were investigated in 28 players who completed a volleyball specific test. Also, masticatory electromyographic tests were performed. The mean pinpoint accuracy was significantly higher with a mouthguard (68.6±9.3 vs. 64.0±7.0 points from 100; p< 0.006). However, differential mouthguard effects were seen, and three subgroups were classified: Group 1 (markedly improved pinpoint accuracy), Group 2 (improved pinpoint accuracy), and Group 3 (reduced pinpoint accuracy). Group 1 had a high masseter resting tone, the masseter activity was low in MVC (maximum voluntary clench) and increased in BOC (maximum bite on cotton rolls; p< 0.04). This indicates a masseter weakness, which would be compensated by a mouthguard. In Group 2, the masseter activity in MVC was high-normal with an imbalance which was improved in BOC (p< 0.01), indicating a possible mouthguard benefit. In Group 3, MVC and BOC were in a high-normal range and showed no relevant deficits. In these subjects the mouthguard had adverse effects. Overall, subjects with masticatory deficits had a benefit from the mouthguard in pinpoint accuracy. Positive or negative mouthguard responders may be detectible from electromyographic tests.

scholarly journals Pharmacokinetics and Tolerability of Oseltamivir Combined with Probenecid

2008 ◽  
Vol 52 (9) ◽  
pp. 3013-3021 ◽  
Author(s):  
Mark Holodniy ◽  
Scott R. Penzak ◽  
Timothy M. Straight ◽  
Richard T. Davey ◽  
Kelvin K. Lee ◽  
...  
Keyword(s):  
Geometric Mean ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Data ◽  
Oseltamivir Carboxylate ◽  
Versus Group ◽  
Group 3 ◽  
The Mean ◽  
Group 2 ◽  
Mean Concentration ◽  
Group 1

ABSTRACT Oseltamivir is an inhibitor of influenza virus neuraminidase, which is approved for use for the treatment and prophylaxis of influenza A and B virus infections. In the event of an influenza pandemic, oseltamivir supplies may be limited; thus, alternative dosing strategies for oseltamivir prophylaxis should be explored. Healthy volunteers were randomized to a three-arm, open-label study and given 75 mg oral oseltamivir every 24 h (group 1), 75 mg oseltamivir every 48 h (q48h) combined with 500 mg probenecid four times a day (group 2), or 75 mg oseltamivir q48h combined with 500 mg probenecid twice a day (group 3) for 15 days. Pharmacokinetic data, obtained by noncompartmental methods, and safety data are reported. Forty-eight subjects completed the pharmacokinetic analysis. The study drugs were generally well tolerated, except for one case of reversible grade 4 thrombocytopenia in a subject in group 2. The calculated 90% confidence intervals (CIs) for the geometric mean ratios between groups 2 and 3 and group 1 were outside the bioequivalence criteria boundary (0.80 to 1.25) at 0.63 to 0.89 for group 2 versus group 1 and 0.57 to 0.90 for group 3 versus group 1. The steady-state apparent oral clearance of oseltamivir carboxylate was significantly less in groups 2 (7.4 liters/h; 90% CI, 6.08 to 8.71) and 3 (7.19 liters/h; 90% CI, 6.41 to 7.98) than in group 1 (9.75 liters/h; 90% CI, 6.91 to 12.60) (P < 0.05 for both comparisons by analysis of variance). The (arithmetic) mean concentration at 48 h for group 2 was not significantly different from the mean concentration at 24 h for group 1 (42 ± 76 and 81 ± 54 ng/ml, respectively; P = 0.194), but the mean concentration at 48 h for group 3 was significantly less than the mean concentration at 24 h for group 1 (23 ± 26 and 81 ± 54 ng/ml, respectively; P = 0.012). Alternate-day dosing of oseltamivir plus dosing with probenecid four times daily achieved trough oseltamivir carboxylate concentrations adequate for neuraminidase inhibition in vitro, and this combination should be studied further.

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