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The Lower to Middle Paleolithic transition (~400,000 to 200,000 years ago) is marked by technical, behavioral, and anatomical changes among hominin populations throughout Africa and Eurasia. The replacement of bifacial stone tools, such as handaxes, by tools made on flakes detached from Levallois cores documents the most important conceptual shift in stone tool production strategies since the advent of bifacial technology more than one million years earlier and has been argued to result from the expansion of archaic Homo sapiens out of Africa. Our data from Nor Geghi 1, Armenia, record the earliest synchronic use of bifacial and Levallois technology outside Africa and are consistent with the hypothesis that this transition occurred independently within geographically dispersed, technologically precocious hominin populations with a shared technological ancestry.

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Neanderthal populations of the southern and northern Caucasus became locally extinct during the Late Pleistocene. The timing of their extinction is key to our understanding of the relationship between Neanderthals and anatomically modern humans (AMH) in Eurasia. Recent re-dating of the end of the Middle Palaeolithic (MP) at Mezmaiskaya Cave, northern Caucasus, and Ortvale Klde, southern Caucasus, suggests that Neanderthals did not survive after 39 ka cal BP (thousands of years ago, calibrated before present). Here we extend the analysis and present a revised regional chronology for MP occupational phases in western Georgia, based on a series of model-based Bayesian analyses of radiocarbon dated bone samples obtained from the caves of Sakajia, Ortvala and Bronze Cave. This allows the establishment of probability intervals for the onset and end of each of the dated levels and for the end of the MP occupation at the three sites. Our results for Sakajia indicate that the end of the late Middle Palaeolithic (LMP) and start of the Upper Palaeolithic (UP) occurred between 40,200 and 37,140 cal BP. The end of the MP in the neighboring site of Ortvala occurred earlier at 43,540-41,420 cal BP (at 68.2% probability). The dating of MP layers from Bronze Cave confirms that it does not contain LMP phases. These results imply that Neanderthals did not survive in the southern Caucasus after 37 ka cal BP, supporting a model of Neanderthal extinction around the same period as reported for the northern Caucasus and other regions of Europe. Taken together with previous reports of the earliest UP phases in the region and the lack of archaeological evidence for an in situ transition, these results indicate that AMH arrived in the Caucasus a few millennia after the Neanderthal demise and that the two species probably did not interact.

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OBJECTIVE: To compare the dosing requirements and international normalized ratios (INRs) associated with two bioequivalent crystalline warfarin sodium products in patients with chronic atrial fibrillation. METHODS: A multicenter, single-blind (prescriber), randomized, crossover evaluation of Apothecon warfarin and DuPont warfarin (Coumadin) was conducted in consenting adults with chronic or paroxysmal atrial fibrillation who had been receiving DuPont warfarin chronically for the prevention of thromboembolism. Patients were randomly assigned to initially either continue DuPont warfarin or receive Apothecon warfarin for four weeks, with weekly evaluation of dosage and INR changes, safety, and efficacy. Subsequently, patients crossed over and received the other product for four weeks. RESULTS: There were 113 patients randomized to receive study treatment. Neither the propensity for a dosage change or an INR change nor the magnitude of a dosage change or INR change appeared related to a particular warfarin product (NS for each variable after each study period). After four weeks of treatment, the same number of patients (n = 7) experienced a > or = 20% change in warfarin dosage from the respective baseline with each product. The number of patients with INRs outside the desired protocol range after four weeks of treatment was similar for both groups (< 1.8, n = 9 for both products, or > 3.2, n = 9 for DuPont, n = 10 for Apothecon). No major hemorrhagic or thromboemoblic events occurred. CONCLUSIONS: The results of this study show that Apothecon warfarin and DuPont warfarin provide equivalent anticoagulation in patients with chronic or paroxysmal atrial fibrillation.

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Ten healthy male volunteers received two doses of tobramycin (2 mg/kg) in a crossover fashion, first by intravenous piggyback (IVPB), then by the CRIS infusion system after a washout period. Serum samples were drawn both during and after the infusions. Twenty-four-hour urine collections were assayed for tobramycin. Residual fluid from the lines of both delivery systems was measured and assayed for tobramycin concentration. All samples were run in duplicate, using an enzyme-multiplied immunoassay technique assay. The results indicate that there was a statistically higher amount of drug delivered via the CRIS system (98.3 +/- 0.3% versus 90.4 +/- 2.3%). No significant difference was found in urinary recovery between the two groups. Peak serum levels were significantly higher with the CRIS system, with 8/10 subjects having at least one serum level greater than 10 micrograms/ml, as compared to 0/10 when given by IVPB. Peak serum levels occurred at 30 min in all subjects given tobramycin through the CRIS system, compared to 50-60 min when delivered by IVPB. This difference in peak serum levels is primarily related to the rate of drug delivery and to the difference in the dose delivered to each subject. The significance of the serum concentration profiles is discussed.

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Graduates of the University of California at San Francisco (UCSF) doctor of pharmacy degree program were surveyed to determine the effect of postgraduate pharmacy residency or fellowship training on the professional outcomes of these graduates. In 1982, a 39-item questionnaire was sent to 1061 UCSF School of Pharmacy alumni who had graduated in the years 1970 through 1981. The survey addressed several issues, including the graduates' general attitudes toward the profession of pharmacy, their practice patterns, and their professional activities. The response rate of the survey was 72%. Of the survey respondents, 30% had completed or were currently involved in a residency or fellowship program. Both postgraduates (PGs) and non-postgraduates (NPGs) indicated an overall satisfaction with life and the pharmacy profession as a whole. A greater fraction of PGs than NPGs worked in the hospital setting and held positions with varied job components (i.e., clinical, managerial, teaching, and operational activities). First-position salaries for both groups were the same regardless of postgraduate training status. Gender, rather than postgraduate status, was the major determinant of annual changes in salary, especially among men PGs. For managers, both men PGs and men NPGs had a greater change in mean salary per year of experience than their women counterparts. Of those graduates who did not hold management positions, men had a greater change in mean salary per year of experience than women. PGs had greater involvement in professional, educational, and publication activities than NPGs, and a smaller percentage of PGs than NPGs left the profession.(ABSTRACT TRUNCATED AT 250 WORDS)

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Among 2,004 patients who underwent their first coronary artery bypass graft operation between January 1970 and December 1980 without concomitant valve replacement or aneurysmectomy, life-table survival was 89% at 5 years and 80% at 8 years after surgery. In a multivariate Cox model analysis, the independent correlates of long-term survival were emergent operation with cardiogenic shock (multivariate mortality rate ratio [RR] = 14.0), use of a postoperative intraaortic balloon pump (RR = 3.9), ejection fraction less than 50% (RR = 2.4), preoperative history of congestive heart failure (RR = 2.2), cardiopulmonary bypass time (RR = 1.4 for each 30-minute increment), uncorrected mitral regurgitation (RR = 1.5 for each increment of angiographic gradation), left main coronary artery narrowing (RR = 1.7) and diabetes (RR = 1.6). After controlling for these factors, age, sex and the percentage of narrowings that were bypassed were not independent correlates of long-term survival.

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Graduates of the University of California at San Francisco (UCSF) Doctor of Pharmacy program from 1970 to 1981 were surveyed to determine their practice patterns, professional activities, and attitudes toward the profession of pharmacy. Of 1061 surveys mailed in September 1982, 752 (72%) were returned. A majority of respondents indicated that they would choose pharmacy as a profession again if starting over and that they would advise a friend to enter the profession. The private hospital setting was the practice site cited most frequently by respondents. Over one third of practicing pharmacists were actively enrolled in or had completed advanced pharmacy training. California was the practice location for 84% of respondents; only one third indicated that salary was very important or somewhat important in their decision to practice at their current location. A large percentage of respondents were involved in teaching, community service activities, and professional associations. Most entry-level UCSF Pharm.D. graduates are satisfied with their professional status and find opportunities for advancement.

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The solubility of phenytoin sodium injection of two manufacturer's was studied in three intravenous fluids, 0.9% sodium chloride, lactated Ringer's, and four manufacturers 5% dextrose injections. Phenytoin sodium for injection was added to 250 ml of an intravenous fluid to give calculated initial concentrations of 0.40, 0.98, 2.38, and 4.55 mg/ml. The pH of each solution was determined before and after the addition of phenytoin. Visual examination and nephelometric measurements for crystals were performed at various times between 5 and 1440 minutes after mixing. Phenytoin concentration was determined by spectrophotometry at these times; nephelometric measurements were done on unfiltered samples. The concentration of phenytoin declined rapidly in all dextrose solutions but at different rates for each brand. A greater stability was demonstrated when phenytoin was diluted in 0.9% sodium chloride and lactated Ringer's injections. Mean concentrations in excess of 95% of initial concentration were maintained for eight hours in those fluids. The two brands of phenytoin sodium injection did not differ consistently with respect to solubility. Crystals were observed in all dextrose solutions; nephelometric measurements indicated crystals were present in all solutions. The pH of all solutions increased sharply upon addition of phenytoin sodium injection. It is concluded that 0.9% sodium chloride and lactated Ringer's injections are suitable diluents for the intravenous administration of phenytoin. Factors other than pH and cosolvent concentration may affect phenytoin stability in dextrose solutions.

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The removal of phenytoin by hemodialysis was determined in seven uremic patients. Four patients were receiving phenytoin sodium for therapeutic purposes; three received one dose each intravenously to quantitate its disposition in uremia. The drug was measured in whole blood, plasma, saliva, and dialysate. Only 2% to 4% of the intravenous dose was recovered in the dialysate. Phenytoin clearance by dialysis was 7 to 14 ml/min; plasma clearance was 53 to 133 ml/min. Since hemodialysis contributes little toward shortening to 11-to-18-hour half-life of phenytoin in the uremic patients, no supplemental dose is necessary for uremic patients undergoing hemodialysis.

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Removal of phenytoin by hemodialysis was determined in a uremic patient. The rate of appearance of the drug in dialysate, the plasma concentration with time, and the plasma clearance by dialysis were measured. Plasma protein binding of phenytoin was also determined. In spite of greatly reduced plasma protein binding in the uremic patient, removal rate was observed to be less than 10% of the rate of presentation of the dialyzer. During the 6-hr period of dialysis, the plasma concentration showed little change. The amount collected in the dialyase, 43.6 mg, was only a small fraction of drug in the body. These results indicate that replacement of phenytoin based on the amount of drug removed by dialysis is unnecessary in chronically dialyzed uremic patients. In addition, the utility of hemodialysis in phenytoin overdose is questioned.

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Long electrocardiographic strips were analyzed from five patients who exhibited periods of typical "concealed bigeminy," i. e., recurrent unifocal extrasystoles which were separated from one another by odd numbers of normally conducted sinus beats. However, in each of these patients, there were periods in which one of three different variants of concealed bigeminy was observed. Three patients displayed an "even number" variant; i. e., there were large numbers of consecutive extrasystoles which were separated exclusively or preponderantly by even rather than by odd numbers of sinus beats. One other patient exhibited an "interpolated extrasystole" variant: those interectopic intervals which were initiated by an interpolated extrasystole contained an even number of sinus beats, whereas all other interectopic intervals contained an odd number. In the fifth patient, the distribution of the numbers of sinus beats separating extrasystoles was such as to suggest a periodic fluctuation between the classical forms of concealed bigeminy and concealed trigeminy; i. e., a "combined bigeminy and trigeminy" variant.

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