OBJECTIVE Toevaluate effects of gabapentin on activity levels and owner-perceived mobility impairment and quality of life (QOL) in osteoarthritic geriatric cats. DESIGN Blinded, placebo-controlled, randomized crossover-design study. ANIMALS 20 osteoarthritic cats (≥ 10 years old). PROCEDURES Cats received gabapentin (10 mg/kg [4.5 mg/lb]) or placebo treatment, PO, every 12 hours for 2 weeks, followed by the alternate treatment (with no washout period). Activity was assessed with a collar-mounted accelerometer. A client-specific outcome measure (CSOM) questionnaire was used weekly to collect owner assessments of 3 selected activities in which their cats had impaired mobility; QOL ratings (worse, the same, or improved) following crossover to each treatment and for the overall study period were collected at the end of the investigation. Activity counts, CSOM and QOL data, and deterioration in impaired activities (ie, decrease of ≥ 2 points in CSOM scores) associated with treatment crossover were assessed statistically. Adverse events were recorded. RESULTS Gabapentin administration was associated with significantly lower mean daily activity counts (48,333 vs 39,038 counts/d) and significantly greater odds (approx 3-fold change) of CSOM ratings indicating improvement in impaired activities, compared with results for the placebo treatment. A greater proportion of cats had deterioration in impaired activities after the crossover from gabapentin to placebo than when the opposite occurred, but the proportion of cats with worsened QOL did not differ between sequences. Adverse events were noted for 10 cats (9 that completed the study) during gabapentin treatment (sedation, ataxia, weakness, and muscle tremors) and 1 cat during placebo treatment (lethargy). CONCLUSIONS AND CLINICAL RELEVANCE Gabapentin treatment was associated with improvement in owner-identified impaired activities of osteoarthritic cats. Activity levels were lower than those during placebo treatment, and sedation was the most common adverse effect.
OBJECTIVE To evaluate tramadol for treatment of signs of pain and impaired mobility in geriatric cats with osteoarthritis. DESIGN Randomized controlled crossover trial. ANIMALS 24 client-owned geriatric (≥ 10 years old) cats with osteoarthritis. PROCEDURES Otherwise healthy cats with owner-identified mobility impairment and clinical and radiographic evidence of osteoarthritis involving at least 1 appendicular joint were enrolled in the study. Cats were treated with tramadol orally at dosages of 0 (placebo), 1, 2, and 4 mg/kg (0, 0.45, 0.9, and 1.8 mg/lb) twice a day for 5 days, with a 2-day (weekend) washout period between treatments. Mobility was assessed with a collar-mounted activity monitor system, and impairments in activity were assessed with a client-completed questionnaire. RESULTS 17 cats completed the study; 7 cats were withdrawn. There was a significant increase in activity with the 2-mg/kg dosage of tramadol, compared with activity when cats received the placebo. Significantly more owners (11/18) considered their cats to have improved with the 2-mg/kg treatment, compared with all other dosages (6/19 to 8/21). Most owners (17/20 [85%]) considered their cat's global quality of life to have improved during the study. Adverse events, predominantly euphoria, dysphoria, sedation, decreased appetite, and diarrhea, were significantly more frequent with the 4-mg/kg (8/19) and 2-mg/kg (6/18) treatments but not with the 1-mg/kg (2/21) treatment, compared with frequency of adverse events with the placebo (0/21). CONCLUSIONS AND CLINICAL RELEVANCE Results suggested a beneficial effect of twice-daily oral administration of tramadol at a dosage of 2 mg/kg in geriatric cats with osteoarthritis. Adverse events were dose dependent, and caution should be exercised in cats that have concurrent disease or are receiving other drugs that may produce adverse gastrointestinal effects.
When 15-day f e t a l mouse duodenum i s c u l t u r e d f o r 48 hours i n Trowel1 T8 medium, v i l l i do not form and c r y p t s o r c r y p t -l i k e s t r u c t u r e s a r e s c a n t y . I n vivo v i l l i d i f f e r e n t i a t e a t 16 days of --g e s t a t i o n and c r y p t s appear t h r e e days l a t e r . I f t h e same c u l t ur e medium i s supplemented w i t h an o r g a n i c e x t r a c t o f 19-day r a t a m n i o t i c f l u i d w e l l d i f f e r e n t i a t e d c r y p t s a r e p r e s e n t i n t h e exp l a n t s a f t e r 48 hours of c u l t u r e . This e f f e c t was a t t r i b u t e d t o t h e presence of a c r y p t d i f f e r e n t i a t i o n f a c t o r (CDF) i n t h e amn i o t i c f l u i d . When f e t a l duodenum i s c u l t u r e d w i t h immersed Eragments (25 mg) of 19-day f e t a l r a t v i s c e r a l yolk s a c (VYS) o r w i t h T8 medium c o n d i t i o n e d by a 24 hour i n c u b a t i o n w i t h VYS fragments, a high CDF a c t i v i t y i s observed. VYS incubated f o r 6 hours i n T8 medium is completely d e g r a n u l a t e d and t h e medium e x h i b i t s a s t r o n g CDF a c t i v i t y . S u b c e l l u l a r f r a c t i o n a t i o n of VYS by d i f f e r e n t l a l c e n t r i f u g a t i o n s u c r o s e r e v e a l t h a t t h e most a c t i v e f r a c t i o n 9. .showing CDF a c t l v l t y 1 s t h e r i c h e s t i n l a r g e g r a n u l e s . Human yolk s a c was taken from a 38-39 day embryo following a p r e v e n t i v e abort i o n ( t u b a 1 i m p l a n t a t i o n ) . When 15-day f e t a l inouse duodenum i s c u l t u r e d i n presence of h a l f of t h e human yolk s a c (HYS), v i l l i and c r y p t s d i f f e r e n t i a t e i n t h e duodenal segments. I t a p p e a r s t h a t HYS a l s o h a s a CDF a c t i v i t y . (Supported by g r a n t No. Previous studies have demonstrated a constant fetal cerebral 0 2 consumption over a range of arterial 0 2 content (Ca02) from 5 to 1 mM. T o determine t h e e f f e c t of such hypoxia on t h e "nonvital" tissues, w e measured hindlimb 0 2 consumption (Go2) in 5 fetal sheep (8-16 days post-op). Four t o six sample sets for hemoglobin concentration expressed a s oxygen capacity and 0 2 saturation were drawn from t h e external iliac a r t e r y (IA) and vein during a control period and a f t e r equilibration at progressively decreasing levels of arterial 0 2 saturation (Sa02, Oh). Hypoxia was produced by maternal common internal iliac a r t e r y occlusion yielding fetal CaO2 from 4.93 t o 0.95 mM. Blood flow (F, mlfmin) t o t h e pelvic limb was measured continuously with an ultrasonic blood flow transducer(Transonics Systems, Inc) placed around t h e IA. C a 0 2 (mM) and Go2 (umfmin) were calculated for e a c h set. Hindlimb F had a tendency to increase while Go2 remained constant t o a C a 0 2 -1.5 mM (Sa02-25°/~), below which both F and \jo2 fell sharply.We compared control with severe hypoxia ( C a 0 2 (1.5 mM) by paired We conclude t h a t 1) t h e f e t u s decieases...
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