Clinical pharmacology of bruceantin by radioimmunoassay

During the phase I clinical trial of a new antitumor agent, bruceantin, the pharmacology was studied in 18 cancer patients. The drug was infused intravenously (IV) for 3 h at doses ranging from 1 to 3.6 mg/m2 per day for 5 days. The plasma drug disappearance curves were biphasic, with a fast initial half-life of less than 15 min. The second half-life (t1/2 beta) varied from 0.7 to 38 h among different patients and was not dose-related. The difference between the t1/2 beta on day 1 and that on day 5 was not significant. In patients with normal liver function, the mean plasma concentration at the end of infusion was 22 ng/ml, and the value of the area under the concentration X time curve (AUC) was 111 (ng/ml)h. In contrast, in patients with abnormal liver function the corresponding values were 115 ng/ml and 830 (ng/ml)h, respectively. In addition, these patients had a slower elimination half-life of 10.9 h and a decreased total clearance of 157 ml/min/m2, as compared with 2.6 h and 671 ml/min/m2, respectively, for the normal group. All these differences were statistically significant. Patients with abnormal liver function developed more severe toxicity, including fever, severe nausea, vomiting, and hypotension. Two patients with severe hepatic dysfunction received a reduced dose and developed no toxicity. These results demonstrated the importance of the effects of liver dysfunction on drug disposition and showed that the dosage should be reduced in patients with hepatic dysfunction.     

Clinical subtypes of cone-rod dystrophy

OBJECTIVE: To determine possible distinct phenotypic subtypes of cone-rod dystrophy. PATIENTS: Thirty-three patients with cone-rod dystrophy (from 25 families) were assessed prospectively on electroretinography, visual field testing, psychophysical threshold profiles, and fundus features. The clinical records of an additional 150 patients with cone-rod dystrophy were examined retrospectively in terms of the classification schema derived from the prospective study. RESULTS: Based on electroretinographic recordings, two major types of cone-rod dystrophy were differentiated. In type 1, cone amplitudes were reduced to a greater degree than were rod amplitudes on electroretinography, while in type 2, cone and rod electroretinographic amplitudes were reduced in equal proportion. These two types were further subdivided on the basis of patterns of visual field loss and threshold elevation. In type 1a, there was a central or paracentral scotoma, and cone thresholds were more elevated centrally than peripherally. In type 1b, there was no central scotoma, and cone thresholds were more elevated peripherally than centrally. In type 2a, there was a central scotoma, cone thresholds were more elevated centrally than peripherally, and rod thresholds were more elevated peripherally than centrally. In type 2b, a partial or complete ring scotoma was present, cone thresholds were more elevated peripherally than centrally, and rod thresholds were more elevated in the midperipheral than in either the central or far peripheral region of the retina. Of the 150 additional patients with cone-rod dystrophy, data sufficient for classification were available for 95 patients, and all but two had findings that were consistent with classification into one of these four subtypes. CONCLUSION: Our results identify four functionally distinct subtypes of cone-rod dystrophy that may be useful for patient counseling and future molecular genetic studies.     

Posture, blood velocity in common femoral vein, and prophylaxis of venous thromboembolism

Might leg elevation and avoidance of poor postures provide better prophylaxis against venous thromboembolism than heparin or mechanical methods? 12 supine subjects tilted in 3 degrees increments from 6 degrees leg-down to 12 degrees leg-up showed linear increase in mean peak blood velocity and reduction in calibre in the common femoral vein (colour-duplex ultrasound). Between horizontal and 6 degrees leg-up, velocity was increased by 17% and diameter reduced by 14%. A ranking of mean peak velocities in six postures (sitting; standing; trunk raised 35 degrees to legs which were first horizontal and then tilted up 6 degrees; supine, first horizontal then 6 degrees leg-up) showed significant increases in velocity between consecutive positions.     

Organization and governance in construction

Transaction cost analysis provides a viable theoretical perspective for the study of organization and governance in construction. The trilateral governance of a client, engineering consultant, and contractors commonly observed in industrial construction projects is detailed. The implications of a professional relationship between the client and the consultant and a clan-type relationship between the consultant and the contractors are discussed within the context of large construction projects.     

Oxygen-hemoglobin equilibrium of normal and glutathione-deficient sheep

Ten patients with severe liver disease and the hepatorenal syndrome underwent exchange transfusions with 9 to 16 units of fresh heparinized blood to improve renal function by either removing a vasoconstrictive substance or adding a vasodilatory substance. One patient recovered from renal failure within ten days without showing natriuresis. The renal function of one patient improved somewhat, but he died 35 days after the transfusion. The other eight aptients died from 1 to 35 days after exchange transfusion, without any appreciable improvement in renal function. In six patients, renin substrate levels increased after the transfusion, but renal function remained unchanged. The results of this study failed to support a humoral concept of pathogenesis of the hepatorenal syndrome.     

Trace element trophic transfer in aquatic organisms: a critique of the kinetic model approach

The bioaccumulation of trace elements in aquatic organisms can be described with a kinetic model that includes linear expressions for uptake and elimination from dissolved and dietary sources. Within this model, trace element trophic transfer is described by four parameters: the weight-specific ingestion rate (IR); the assimilation efficiency (AE); the physiological loss rate constant (ke); and the weight-specific growth rate (g). These four parameters define the trace element trophic transfer potential (TTP = IR.AE/[ke + g]) which is equal to the ratio of the steady-state trace element concentration in a consumer due to trophic accumulation to that in its prey. Recent work devoted to the quantification of AE and ke for a variety of trace elements in aquatic invertebrates has provided the data needed for comparative studies of trace element trophic transfer among different species and trophic levels and, in at least one group of aquatic consumers (marine bivalves), sensitivity analyses and field tests of kinetic bioaccumulation models. Analysis of the trophic transfer potentials of trace elements for which data are available in zooplankton, bivalves, and fish, suggests that slight variations in assimilation efficiency or elimination rate constant may determine whether or not some trace elements (Cd, Se, and Zn) are biomagnified. A linear, single-compartment model may not be appropriate for fish which, unlike many aquatic invertebrates, have a large mass of tissue in which the concentrations of most trace elements are subject to feedback regulation.     

The effect of (2'-5') and (3'-5') phosphodiester linkages on conformational and stacking properties of cytidylyl-cytidine in aqueous solution

Conformational properties of (2'-5') and (3'-5') CpC have been determined by proton magnetic resonance spectroscopy at 220 MHz. The ribose ring structures are predominantly 3E with the exception of the ring from the 2'-phosphate fragment of C(2'-5')pC which exhibits an 2E pucker. Bases are oriented anti with respect to the ribose and the conformations about C4'-C5', C5'-O5', C3'-O3' (C2'-O2') are gg, g'g', and g+ in equilibrium g-, respectively. The dimers exist as mixtures of stacked (g+g+ and g-g- about the P-O(C) bonds) and unstacked species at 20 degrees C. Stacking is estimated to be 35% in both dimers.