Renovasal relationship in patients with uncomplicated hypertensive disease

Aim. To assess the influence of arterial stiffness on the renal filtration function in patients with uncomplicated hypertensive disease. Materials and methods. The study included 88 patients of able-bodied age, suffering from stage III hypertensive disease. The mean age was 50.38 5.19 years. All the patients underwent sphigmopletismography with assessment of cardio-malleolar-vascular index (CAVI1), evaluation of renal filtration function by creatinine and cystatin C levels as well as by calculated glomerular filtration rate (GFR) by creatinine and cystatin C. All the patients were divided into 3 groups according to CAVI1 level: group 1 patients without arterial lesion and CAVI1 8; group 2 patients with borderline changes in arteries and CAVI1 8.08.9; group 3 patients with arterial lesion and CAVI19. Results. No statistically significant differences by clinicoanamnestic characteristics were found out in patients of all groups. In patients of group 1, cystatin level appeared to be statistically significantly lower than in patients of group 2 and 3 (pmg = 0.013). Patients of all groups statistically significantly differed according to GFR by cystatin C (pmg = 0.015). No difference according to creatinine level and GFR by creatinine were registered in the groups. Conclusions. As arterial stiffness by CAVI1 level is increased, there occurs statistically significant aggravation of renal filtration function, assessed by cystatin C level and GFR using the formula CKD-EPI by cystatin C. Changes in the renal filtration function indices were observed within the normal values that shows early preclinical changes.

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A note on the occurrence of isolated melanin pigmented fibres in the white fleece wool of Corriedale sheep

Animal Science ◽

10.1017/s0003356100041969 ◽

1984 ◽

Vol 39 (2) ◽

pp. 311-314 ◽

Cited By ~ 1

Author(s):

M. R. Fleet ◽

J. E. Stafford ◽

C. H. S. Dolling

Keyword(s):

Visual Inspection ◽

Skin Pigmentation ◽

Large Numbers ◽

Group 3 ◽

The Mean ◽

Selection For ◽

Group 2 ◽

Level Group ◽

Group 1 ◽

Skin Pigment

ABSTRACTThe occurrence of melanin pigmented wool fibres in the skirted white fleece wool from 1-year-old Corriedale ewes, having either least (group 1), most (group 3) or an intermediate level (group 2) of black nose skin pigmentation, was investigated. Thirteen of the 87 fleeces analysed had the equivalent of 10 to 389 isolated pigmented fibres per 100 g of scoured wool. The mean diameter of the pigmented fibres was similar to that of the fleece specimens analysed and they occurred singly or in small groups within individual staples. Large numbers of isolated pigmented fibres in fleeces were widely distributed, and constitute a serious problem of identification by visual inspection. Fibre darkness and the number of fleeces found with pigmented wool fibres were two measurements which showed a significant association (P < 0·001 and P < 0·05, respectively) with nose skin pigment group. With one exception from group 2 the results support the suggestion that the usual selection for dark nose skin in this breed may be antagonistic to selection for a white fleece. The pigmented lengths of fibres were found to be independent of nose skin pigment group.

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

Angiology ◽

10.1177/0003319721991410 ◽

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.

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

10.21203/rs.3.rs-736656/v1 ◽

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.

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

Journal of Pharmaceutical Research International ◽

10.9734/jpri/2021/v33i27a31491 ◽

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.

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Serum Bioavailable Testosterone: Assayed or Calculated?

Clinical Chemistry ◽

10.1373/clinchem.2005.052126 ◽

2006 ◽

Vol 52 (3) ◽

pp. 474-481 ◽

Cited By ~ 51

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 >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 <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.

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Specificities in mechanism of erythrocyte deformability disorders in various diseases

Тромбоз, гемостаз и реология ◽

10.25555/thr.2021.1.0965 ◽

2021 ◽

Author(s):

Н.П. Александрова ◽

В.И. Карандашов ◽

Д.А. Кудлай

Keyword(s):

Disease Duration ◽

Normal Values ◽

Common Factors ◽

Erythrocyte Deformability ◽

Mechanical Resistance ◽

Hematocrit Level ◽

Group 4 ◽

Group 3 ◽

Group 2 ◽

Group 1

Введение. Нарушение текучести крови, обусловленное повышением ее вязкости и снижением эластичности эритроцитов, может привести к столь значительным расстройствам центральной гемодинамики и микроциркуляции, что возникает дисфункция органов. Цель исследования: изучение доминирующих специфических механизмов, вызывающих нарушение деформируемости эритроцитов при различных заболеваниях. Материалы и методы. Обследован 121 пациент: с геморрагическим панкреонекрозом (n = 16) без острой сопутствующей сердечно-сосудистой патологии (группа 1); с тромбоэмболией магистральных артерий нижних конечностей (n = 37) с локализацией в подвздошной, бедренной и подколенной артериях, со сроком заболевания от 2 до 3 сут (группа 2); с острым тромбозом магистральных артерий нижних конечностей (n = 32) с ишемией II степени и длительностью заболевания от нескольких недель до нескольких месяцев (группа 3); с острым венозным тромбозом (n = 36), срок заболевания варьировал от 24 ч до 30 сут (группа 4). Для контроля изучены показатели 26 практически здоровых лиц (группа 5). Проведено исследование деформируемости эритроцитов методом фильтруемости, изучали распределение эритроцитов по диаметру, определяли показатель гематокрита и механическую резистентность эритроцитов, исследование белкового состава плазмы проводили спектрофотометрическим способом, измеряли содержание сиаловой кислоты в плазме и в эритроцитах. Результаты. Самые тяжелые нарушения морфологических и физико-химических свойств эритроцитов выявлены у больных геморрагическим панкреонекрозом (группа 1): скорость фильтрации эритроцитов была в 1,8 раза меньше, чем у здоровых людей; диаметр эритроцитов в 1,2 раза, а уровень гематокрита на 9% превышали норму; механическая резистентность была в 2 раза ниже нормальной. По сравнению с нормальными значениями у больных группы 2 диаметр эритроцитов был увеличен на 18%, гематокрит — на 7%, механическая резистентность была снижена на 27%. У пациентов группы 3 деформируемость была снижена на 14%, диаметр эритроцитов превышал норму на 11%, гематокрит — на 5%, механическая резистентность была снижена на 18%. У больных группы 4 деформируемость эритроцитов была практически не нарушена, все остальные параметры эритроцитов также не отличались от нормальных. Заключение. Существуют как специфические факторы, обусловливающие нарушение деформируемости эритроцитов и присущие только конкретному заболеванию, так и общие факторы, изменяющие деформационные свойства эритроцитов, которые сопровождают практически любую патологию. Общими факторами, снижающими деформационные свойства эритроцитов при исследованных нами заболеваниях, являются выраженная диспротеинемия и ацидоз. Background. Blood flow disorders due to its viscosity increasing and erythrocytes elasticity decreasing, may cause significant disturbances of central hemodynamics and microcirculation that lead to organ dysfunction. Objectives: to studythe basic specific mechanisms of erythrocyte deformability impairment in various diseases. Patients/Methods. We examined 16 patients: with hemorrhagic pancreonecrosis (n = 16) without acute comorbid cardiovascular pathology (group 1); with thrombembolia of the main arteries (iliac, femoral and popliteal) of lower extremities (n = 37), and disease duration of 2 to 3 days (group 2); with acute thrombosis (II degree ischemia) of the main arteries in the lower extremities (n = 32), and disease duration from several weeks to several months (group 3); with acute venous thrombosis (n = 36) and disease duration from 24 hours to 30 days (group 4). Group 5 consisted of 26 practically healthy individuals. We measured erythrocytes deformability (by filterability method), erythrocytes diameter distribution, hematocrit and erythrocytes mechanical resistance, plasma proteins composition (spectrophotometrically), sialic acid concentration in plasma and erythrocytes. Results. The most expressive disorders of erythrocytes morphological and physicochemical properties were found in patients with hemorrhagic pancreonecrosis (group 1): erythrocytes filtration rate was 1.8 times less than in healthy people; erythrocytes diameter was 1.2 times and the hematocrit level was 9% above normal; mechanical resistance was 2 times lower than normal. In patients of group 2 erythrocytes diameter was increased by 18%, hematocrit level — by 7%, mechanical resistance was reduced by 27% compared with normal values. In patients of group 3, deformability was reduced by 14%, erythrocytes diameter exceeded the norm by 11%, the hematocrit was by 5% above the norm, mechanical resistance was reduced by 18%. In patients of group 4, erythrocyte deformability practically was not impaired; all other erythrocytes parameters also did not differ from normal values. Conclusions. Erythrocyte deformability impairment caused by both specific factors that are attributable only for specific disease and by common factors that exists in almost any disease. Expressed dysproteinemia and acidosis are common factors that reduce erythrocyte deformability in examined diseases.

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

10.36106/6333041 ◽

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.

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Acute Phase Effect of Memantine Hydrochloride in Experimental Peripheral Nerve Injury

Indian Journal of Neurosurgery ◽

10.1055/s-0039-1695668 ◽

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.

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Prediction of Ergogenic Mouthguard Effects in Volleyball: A Pilot Trial

Sports Medicine International Open ◽

10.1055/a-1036-5888 ◽

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.

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Pharmacokinetics and Tolerability of Oseltamivir Combined with Probenecid

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00047-08 ◽

2008 ◽

Vol 52 (9) ◽

pp. 3013-3021 ◽

Cited By ~ 39

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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