Respiratory therapy as a component of an integrated hospital information system: the Parkland On-Line Information System (POIS).

Information handling is an important part of the activities of health care professionals, and the Parkland On-line Information System (POIS)--a computerized hospital information system--was established to more efficiently handle the processing and storage of information in our institution. Computerization of a respiratory therapy department is more effective if done in the context of a comprehensive, integrated hospital information system. Information and requests for services flow into the respiratory therapy departmental computer from other hospital terminals, and information, such as patient charges and statistical data, flow out of the departmental computer to those requesting such information. POIS is an implementation of the IBM Patient Care System. We have found that a computerized hospital information system can facilitate patient care by easing the burden of information processing.     

Spiro[fluoreneisothiazolidin]one dioxides: new aldose reductase and L-hexonate dehydrogenase inhibitors

The first examples of spiro[fluorene-9,4'- and -9,5'-isothiazolidin]one dioxides (1 and 2) were synthesized and screened for activity as aldose reductase and L-hexonate dehydrogenase inhibitors. Compared to compounds 1, and 9,5'-compounds 2, synthesized from fluorene-9-sulfonamides by alkylation at C(9) with ethyl bromoacetate followed by cyclization, were more active, but relatively nonselective, inhibitors of aldose reductase and L-hexonate dehydrogenase, with IC50 values for in vitro inhibition of both enzymes on the order of 10(-7)-10(-8) M. However, the isomeric 9,4'-compounds 1, prepared by alkylation of fluorene-9-carboxylic acid esters with bromo- or iodomethanesulfonamide followed by cyclization, were more selective inhibitors of L-hexonate dehydrogenase with IC50 values of about 10(-6) M.     

Pharmacokinetics and efficacy of structurally related spirohydantoin and spirosuccinimide aldose reductase inhibitors.

1. Six potent aldose reductase inhibitors (ARI), three spirohydantoin (I to III) and three spirosuccinimide (IV to VI) compounds, showed similar IC50 activities in vitro for the inhibition of rat lens aldose reductase, but their ED50 values in diabetic rats varied as much as 20-fold in the lens and 50-fold in the sciatic nerve tissue. Pharmacokinetic studies were undertaken to investigate these findings. Structure-pharmacokinetic relationships were studied following i.v. administration to cynomolgus monkeys. 2. The clearance (CL) of each spirosuccinimide ARI was faster (greater than 5 times) than that of the corresponding spirohydantoin compound. In both series the CL values of the C(4) methyl and methoxy analogues were 4-fold greater than those for the unsubstituted compounds, although the CL values of the methoxy and methyl derivatives in the same series were not significantly different. 3. The volumes of distribution (Vss) of the spirohydantoins were about one-half those of the corresponding spirosuccinimides, and the Vss values of the parent compounds of both ARI series did not differ dramatically from those of their methyl and methoxy analogues. 4. All six compounds were eliminated from plasma in a biexponential fashion. The half-lives (lambda 1 and lambda 2) of the spirohydantoin compounds were much longer than those of the corresponding spirosuccinimide compounds, and the unsubstituted compounds had longer half-lives than their methyl and methoxy derivatives. The longest lambda 1 and lambda 2 half-lives were observed for imirestat, while two of the spirosuccinimides had the shortest half-lives. 5. These results indicate that the relationships observed between the in vitro and in vivo activities of the six ARI can be attributed to structurally dependent differences in metabolic clearance.     

Comparison of the Pharmacokinetics and Pharmacodynamics of the Aldose Reductase Inhibitors,AL03152 (RS), AL03802 (R), and AL03803 (S)

The pharmacokinetics of AL03152 (RS) and its enantiomers, AL03802 (R) and AL03803 (S), were studied in the Sprague–Dawley rat following intravenous bolus administration. The enantiomers had differing pharmacokinetic profiles, while the racemic compound exhibited pharmacokinetic parameters approximating the mean values of the individual enantiomers. The total clearance (CL_T) values of the two enantiomers were similar, but the intrinsic clearance (Cl_int) was much greater for the S-enantiomer than for the R-enantiomer. The volume of distribution (V_ss) for AL03802 (R) was threefold greater than that for AL03803 (S). The stereoselectivity in V _ss could not be totally accounted for by the slight difference in serum protein binding of the isomers and resulted in a difference in the half-lives of the enantiomers. Only the R-isomer exhibited a persistent terminal elimination phase, consistent with more extensive tissue binding than the S-isomer. AL03152 enantiomers were equivalent in potency assessed from in vitro IC₅₀ values toward rat lens aldose reductase and rat kidney L-hexonate dehydrogenase and lens EC₅₀ values in diabetic rats.     

Habituation reduces novelty-induced FOS expression in the striatum and cingulate cortex

Exposure to novel environments is known to induce c-fos expression in the cingulate cortex and dorsomedial striatum. This study examined the effects of 1, 3, and 7 days of exposure to sequential exposure to three novel environments. It was hypothesized that the ability of novel environment shuttling (NES) would induce c-fos expression as indicated by cells displaying FOS-like immunoreactivity (FLI) in the striatum and cingulate cortex which would decrease with repeated exposure. NES elicited FLI in both the cingulate cortex and striatum when compared to home-cage controls and this effect was attenuated with repeated exposure. Behavioral measures of activity decreased with repeated exposure suggesting that the decrease in FLI may be due to either a reduction in motor activity or increasing familiarity with the environments.     

Gallbladder injuries resulting from blunt abdominal trauma: an experience and review.

Over a seven-year period from 1973 through 1979, 31 patients with blunt gallbladder trauma were treated at the Maryland Institute for Emergency Medical Services Systems. Twenty patients had contusions, ten patients had avulsions and one patient had a perforation of the gallbladder. None of the gallbladder injuries were suspected preoperatively. Twenty-eight of the 31 patients had a diagnostic peritoneal lavage performed on admission, all were positive for blood; bile was not grossly evident. Among the 30 patients, there were 75 associated intraabdominal injuries; there were 25 liver injuries. Five patients died, none as a result of their gallbladder injury. Cholecystectomy is suggested as the definitive procedure of choice for severe contusions and for perforating and avulsive injuries to the gallbladder. Cholecystostomy is indicated in a few patients and should be regarded as a temporary procedure. A review of the English literature shows a total of 101 patients (including the 31 of this study) with gallbladder injuries secondary to blunt trauma. The most commonly reported injury was perforation. The 20 contusions described in the present study are the first such injuries reported.     

Streptozotocin therapy in 22 cancer patients.

Twenty-two cancer patients were treated with streptozotocin (SZN) in six weekly intravenous doses of 1.0-1.5 g/m2. The results of the initial courses of therapy include 3 complete and 2 partial responses, 11 patients with no change, 4 with progression, and 2 deaths due to tumor progression. Three additional deaths also due to tumor progression occurred in previously responding patients. All responses were in patients with pancreatic tumor. Toxicity consisted of transient proteinuria in 11/15 patients, transient azotemia in 11/18 patients, marked reduction of creatinine clearance in 1 patient, burning pain at site of injection, nausea, and vomiting in 20/22 patients, change of FBS from pretherapy to post-therapy of at least 10 mg/100 ml in 11/17 patients, significantly decreased platelet count in 1/22 patients, decreased Hgb in 2/22 patients, and duodenal ulcer in 2/22 patients. A reduced dosage schedule and combination with other drugs known to be effective in pancreatic tumors deserves further investigations.     

Sepsis and upper gastrointestinal hemorrhage due to duodenal-caval fistula: complications of delayed treatment of a penetrating abdominal injury (case report).

Sepsis and upper gastrointestinal hemorrhage due to duodenal-caval fistula complicated delayed treatment of an abdominal gunshot wound. Gastric and duodenal decompression, external drainage of the duodenal repair, and caval ligation are preferred for delayed treatment of combined duodenal and infrarenal vena caval injuries.