Down-regulation of muscarinic receptors in the striatum of organophosphate-treated swine

Subacute (daily) administration of diisopropylfluorophosphate (DFP) to male swine (Yorkshire white) resulted in a 97% inhibition of cholinesterase and a decrease of [3H]quinuclidinyl benzilate [( 3H]QNB) binding sites in homogenates of striata by approximately 50% after 14 days. The maximal density of receptors (Bmax) decreased from 2.1 +/- 0.3 to 1.0 +/- 0.2 pmole/mg protein. There was no significant change in the dissociation constant (Kd) for [3H]QNB binding (control: 52.6 +/- 10.7 pM; 7-day: 57 +/- 2.8 pM). Carbachol displacement of [3H]QNB binding yielded data best fit by a two-binding site model. The dissociation constants were KiL = 115 +/- 62 microM (55 +/- 3%) and KiH = 1.8 +/- 0.7 microM (45 +/- 3%), respectively, for the low- and high-affinity states. Seven-Day treatment with DFP reduced the percentage of high-affinity receptors to 22 +/- 8.6%, but affected neither the low- nor the high-affinity Kd (100 +/- 20 and 2 +/- 0.6 microM). With the addition of Mg2+, striatal homogenates had low- and high-affinity receptors in the proportion of approximately 1 to 1. In the presence of Gpp(NH)p + Mg2+ the ratio of high- to low-affinity receptors was 3:1 in homogenates of control tissue (to 26 +/- 5%). This treatment had no effect on this ratio in homogenates of tissue from 7-day DFP-treated swine (3:1) since it was already 3:1. Pirenzepine displacement of [3H]QNB binding was best described by a two-binding site model, with Ki values of 38 +/- 14 and 201 +/- 78 nM, which represent 74 and 26% of the binding sites, respectively. The high affinity Kd value was unchanged following 7 days of DFP treatment (24 +/- 5 nM). There appears to be little change in the displacement curves for pirenzepine inhibition of [3H]QNB binding. This suggests that about 75% of the receptors are of the M1 subtype. Thus, subacute administration of DFP causes not only a decrease in the number of receptors, but also a change in the proportion of agonist affinity states which is related to the interaction of the guanine nucleotide binding protein and the muscarinic receptor.     

Revision endoscopic frontal sinus surgery with surgical navigation.

BACKGROUND: Revision surgery of the frontal sinus remains one of the most difficult operations for the endoscopic surgeon. Most agree that knowledge and recognition of its complex anatomy and sparing of frontal recess mucosa are keys to a successful operation. The use of surgical navigation systems may allow for more precise dissections and greater rates of frontal recess patency. METHODS: Retrospective review of all patients undergoing revision endoscopic frontal sinus surgery with surgical navigation was performed with a minimum 24-month follow-up. RESULTS: Sixty-seven patients underwent revision endoscopic frontal sinus surgery with surgical navigation. The average follow-up was 32 months. Fifty-eight (86.6%) had a patent frontal recess and significant subjective improvement in symptoms. No patient underwent external frontal sinus obliteration, and there were no major complications. CONCLUSIONS: Endoscopic techniques with surgical navigation are effective in revision frontal sinus cases. The dissection of remnant agger nasi, obstructing frontal and supraorbital cells are necessary to widen the anterior-posterior as well as the medial-lateral dimensions of the recess. Computer navigational systems appear to serve as a valuable adjunct in preoperative planning and safe intraoperative dissection.     

Factors causing interrupted delivery of enteral nutrition in trauma intensive care unit patients.

BACKGROUND: The intent of this study was to ascertain the adequacy of delivery of enteral nutrition (EN) to critically ill adult multiple trauma patients and to identify potential detrimental factors that affect EN delivery. METHODS: Retrospective observational study. Trauma intensive care unit (TICU) in a university-affiliated hospital. Adult patients (>/=18 years of age) admitted to the TICU who received enteral feeding. RESULTS: Fifty-six adult patients were enrolled for study. Patients received, on average, 67% +/- 19% of what was prescribed for 5.7 +/- 2.0 days. A total of 222 occurrences for temporary discontinuation of tube feeding were identified. Gastrointestinal intolerance, as defined by a gastric residual volume of >150 mL, abdominal pain, or >3 liquid stools per day, accounted for only 11% of the occurrences for discontinuation of feeding. Surgery (27%) and diagnostic procedures (15%) represented the majority of reasons for inadequate nutrient delivery. Minor factors for EN interruptions were mechanical feeding tube problems (8%), pharmacy delivery delay (4%), and miscellaneous factors (3%). Multiple and unknown reasons contributed to 14% and 18% of the occurrences, respectively. CONCLUSIONS: Surgery and diagnostic procedures accounted for the largest factor in enteral feeding discontinuations in our critically ill trauma patients. Gastrointestinal intolerance contributed a minor role in the temporary discontinuation of enteral feeding.     

Comparative study of laser versus radiofrequency myringotomy in rabbits: The effectiveness of mitomycin C application.

OBJECTIVE: To compare laser-assisted tympanostomy (LAT) with radiofrequency myringotomy (RFM), as well as the effectiveness of mitomycin C (MC) on the above techniques, in rabbits. STUDY DESIGN: Experimental animal research protocol. SETTING: University of Crete, School of Medicine, Medical Experimental Education and Research Center. METHODS: Bilateral myringotomies were performed under general anesthesia on 40 rabbits. LAT was performed on 20 animals (40 ears) and RFM on the remaining 20 animals (40 ears). MC (0.3 mg/mL) pledgets were applied to the right ears and saline pledgets to the left ears. Animals were monitored weekly using otomicroscopy until myringotomy closure. Kaplan-Meier survival techniques were used to compare myringotomy patency times. INTERVENTIONS: Under general anesthesia, bilateral LAT was performed on 20 rabbits and bilateral RFM on 20 rabbits. MAIN OUTCOME MEASURES: Myringotomy patency time. RESULTS: The mean patency times of the saline-treated ears were: 1.85 weeks (95% confidence interval [CI], 1.556-2.144 wk) for the LAT group and 1.70 weeks (95% CI, 1.494-1.906 wk) for the RFM group. This difference was not significant (p > 0.5). MC application significantly prolonged mean patency time (p < 0.0001) in both LAT and RFM groups. The mean patency times in the MC-treated ears were 5.45 weeks (95% CI, 5.226-5.674 wk) for the LAT group and 5.55 weeks (95% CI, 5.285-5.815 wk) for the RFM group. This difference was not significant (p > 0.5). CONCLUSION: There is no significant difference in myringotomy patency times between LAT and RFM techniques in rabbits, whereas MC significantly prolongs the patency rate of either technique.     

Serum and peritoneal dialysate thyroid hormone levels in patients on continuous ambulatory peritoneal dialysis

Thyroid function tests were performed on 16 clinically euthyroid patients with end-stage renal failure undergoing regular haemodialysis or continuous ambulatory peritoneal dialysis and compared with 8 healthy subjects. The patient groups were carefully matched, especially regarding relative duration of dialysis (mean of 24 months). Total serum thyroxine, total triiodothyronine, free thyroxine, free triiodothyronine and reverse triiodothyronine were significantly lower in both patient groups than control. The thyrothrophin response to the standard thyrotrophin-releasing hormone test was delayed and blunted. Using a novel concentration technique we measured loss of T4 in peritoneal dialysate effluent and found it to be approximately 10% of daily thyroidal T4 release.